<![CDATA[BioE PhD Proposal Presentation- Ishita Kumar]]> 27917 Advisor: Corey J. Wilson, Ph.D. (School of Chemical and Biomolecular Engineering, Georgia Institute of Technology)

Committee:

John Blazeck, Ph.D. (School of Chemical and Biomolecular Engineering, Georgia Institute of Technology)

Hang Lu, Ph.D. (School of Chemical and Biomolecular Engineering, Georgia Institute of Technology)

Ravi Kane, Ph.D. (School of Chemical and Biomolecular Engineering, Georgia Institute of Technology)

Richard M. Murray, Ph.D. (Division of Biology and Biological Engineering, California Institute of Technology)

 

Next-Generation Biosecurity: Advancing Tools for Multi-Layer Security

The rapid expansion of synthetic biology from laboratory spaces to industrial and healthcare sectors has brought about concerns of unwanted release of genetically modified organisms and protection of biological intellectual property. Current physical and operational security measures for these assets can be comprised by theft or accidental release. This thesis proposes the designing, building, and testing of a next-generation biosecurity system that is intrinsic to the engineered organism. While prior studies have demonstrated basic intrinsic security measures, there is considerable value in advancing the state of the art with novel tools, multi-layer security platforms, and the introduction of penetration testing. First, an 8-digit biological keypad will be developed in Escherichia coli for 2-input and 3-input passcodes to protect a biological asset. This technology will be combined with toxin-based penalties to design a first-of-its-kind Biohackathon challenge. Furthermore, a novel ‘Command Center’ for editing biological programs will be shown in situ using an engineered E. coli strain. The Command Center would be a promising tool for biosecurity applications. Finally, an authentication system will be engineered through synthetic auxotrophy, and will be deployed with other biosecurity measures to a design a second Biohackathon challenge. Together, these technologies will establish a foundation for integrating multi-layer biosecurity into biotechnology.

]]> Laura Paige 1 1715794895 2024-05-15 17:41:35 1715794975 2024-05-15 17:42:55 0 0 event BioE PhD Proposal Presentation- "Next-Generation Biosecurity: Advancing Tools for Multi-Layer Security" - Ishita Kumar

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<![CDATA[BioE MS Thesis Defense Presentation- Fernando Martinez]]> 27917 Committee Members:
Young Jang, PhD (advisor) (Emory University)

Shuichi Takayama, PhD (co-advisor) (Georgia Institute of Technology)

Valeria Milam, PhD (Georgia Institute of Technology)

 

3D FIBRIN MICROGEL SYSTEM FOR SENESCENSE DETECTION

With the scientific advances and improvements in quality of life over the past century, the percentage of the aged population has been steadily increasing. With age comes a multitude of age-related diseases including cardiovascular disease, hypertension, cancer, osteoporosis, Alzheimer’s disease, and more. One of the 12 hallmarks of aging, cellular senescence, has been directly linked to age-related pathologies. Treatment of cellular senescence via senolytics is a growing niche in aging research, due to the promise it shows in managing senescence accumulation and age-related diseases. Despite growing use of 3D systems in research, there is a lack of models for age-related drug screening. This thesis aims to refine a bio-printed fibroblast-containing fibrin gel model for the detection of cellular senescence. This fibrin microgel model closely mimics the early stages of wound healing, where clot formation occurs, and is subsequently degraded by a process known as fibrinolysis. First, we sought to establish reproducibility in the system. Gel parameters were studied to determine their relationship with an established readout of fibrinolysis time, and ways to reduce variability in the system were investigated. Second, different methods of senescence were tested to determine sensitivity of the fibrin gel model to cellular senescence. Comparing the effects of multiple forms of senescence in the model is necessary due to different pathways of senescence activation and potential differences in senescence associated secretory phenotypes (SASPs). Overall, the work accomplished in this thesis could help establish a novel marker for rapid cellular senescence detection and a tool for senolytic drug discovery and screening.

]]> Laura Paige 1 1715010558 2024-05-06 15:49:18 1715010612 2024-05-06 15:50:12 0 0 event BioE MS Thesis Defense Presentation- "3D FIBRIN MICROGEL SYSTEM FOR SENESCENSE DETECTION" - Fernando Martinez

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<![CDATA[BioE PhD Proposal Presentation- Alexander Heiler]]> 27917 Advisor: Susan N. Thomas, Ph.D. (Woodruff School of Mechanical Engineering, Georgia Institute of Technology)

 

Committee:

M.G. Finn, Ph.D. (School of Chemistry and Biochemistry, Georgia Institute of Technology)

John Blazeck, Ph.D. (School of Chemical and Biomolecular Engineering, Georgia Institute of Technology)

Julie Champion, Ph.D. (School of Chemical and Biomolecular Engineering, Georgia Institute of Technology)

Jihoon Kim, Ph.D. (School of Integrative Engineering, Chung-Ang University)

 

Surface-tunable nanoparticles for studying lymphatic delivery dynamics

The properties of drug delivery vehicles are often modulated to better overcome biological barriers and enhance the delivery of bioactive molecules to their intended target, such as immunotherapeutic delivery to mediate the immune response to disease. In this presentation, I will describe my work in engineering the surface properties of poly(propylene sulfide) nanoparticles to modulate their transport behaviors and enable novel drug delivery dynamics and mechanisms. Using in vitro models recapitulating subcutaneous drug administration and uptake into the lymphatic system, the nanoparticle architecture and transport properties were characterized in the context of the copolymer properties comprising the nanoparticle surface. Furthermore, the nanoparticle surface was functionalized to display two reactive groups capable of conjugating two distinct antibodies in controlled ratios, enabling complex interactions with lymphocyte surface receptors. Additionally, a light-responsive cleavable linker will be used to form a photoactivatable fluorescent tracer able to evaluate nanoparticle delivery dynamics within the lymph node. This proposal enhances nanomaterial tools to evaluate nanoparticle delivery across different biological barriers in support of immunotherapeutic delivery to modulate the immune response.

]]> Laura Paige 1 1715010414 2024-05-06 15:46:54 1715010486 2024-05-06 15:48:06 0 0 event BioE PhD Proposal Presentation- "Surface-tunable nanoparticles for studying lymphatic delivery dynamics" - Alexander Heiler

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<![CDATA[2024 IBB Distinguished Lecture]]> 27195 M. Richard Shen, Ph.D.
Managing Director and Founder
RS Technology Ventures, LLC

*This will be an in-person event.

ABSTRACT
Periods of accelerated discovery can be defined by the technologies that are created and their costs. Almost all of us are familiar with the story about semiconductors, integrated circuits, and Moore’s Law. The development of this compute technology has placed what would be building-sized supercomputers from the 1980s into simple, handheld devices in the 2020s. However, many may not be familiar with the story of the development of genetic analysis systems in the first decade of this century by a startup called Illumina. This startup has transformed genetic analysis by first creating the leading genotyping platform and then developing the dominant next-generation sequencing (NGS) platforms.

There are many factors that contribute to the successful development of these platforms, such as corporate culture, strategic vision, technology management and product development. We will focus on some of these factors and how they were used to develop products that have transformed biological analysis. We will also discuss how discoveries enabled by these scalable technologies have created new clinical applications and avenues of research. The high specificity and tunable sensitivity of NGS have enabled the development of non-invasive prenatal testing, cancer therapy selection and detection of residual disease from blood samples. The low-price points in these technologies have created markets in consumer genomics, forensic genealogy, and population-scale whole-genome sequencing.

The current period of accelerated biological discovery is being driven by robust genetic analysis tools, accessible compute infrastructure and low price.

BIO
Richard Shen, Ph.D., is an innovator, investor, and business executive. He has over 25 years of experience in the genomics and molecular diagnostics markets. He is active in the investment community as part of NuFund in San Diego and is managing director of RS Technology Ventures, LLC. He is currently on the Board of Directors of public and private companies in the liquid biopsy and diagnostics markets.

Richard held many senior executive positions in his career. Most recently at PacBio he was Sr. Vice President of R&D, responsible for software and bioinformatics, applications, and platform development. Prior to that he was President of Omniome, a start-up that developed a high-accuracy Next Generation Sequencing (NGS) platform. In the year 2000, Richard joined a startup that was Illumina. In his 16-year career at Illumina, he was responsible for scaling and running operations, development of the genotyping and NGS platforms and Oncology R&D.

Richard holds several key patents in the fields of nucleic acid analysis and sequencing. One of his patents enabled the development of a process to sequence the human genome for less than $1,000.

Richard is an alumnus of UCLA (B.S.) and LSU Medical Center (Ph.D.). He did postdoctoral fellowships at University of Michigan Medical Center to study gene therapy and Lawrence Livermore National Laboratories to study variation in DNA repair genes. Richard is a certified director from the UCLA Anderson School of Management.

]]> Colly Mitchell 1 1714049421 2024-04-25 12:50:21 1714050767 2024-04-25 13:12:47 0 0 event “From Underdog to Market Leader: The Development of Genetic Analysis Tools by Illumina in the Early Years” - M. Richard Shen, Ph.D., Managing Director and Founder, RS Technology Ventures, LLC

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<![CDATA[IBB Seminar]]> 27195 A special seminar organized by IBB's Bioengineering Interdisciplinary Graduate Program in celebration of BioE Day.

Ricardo Cruz-Acuña, Ph.D.
Assistant Professor of Cancer Engineering
College of Dental Medicine
Columbia University Medical Center


ABSTRACT
Clinical studies have found a correlation between extracellular matrix (ECM) stiffening and the progression of esophageal adenocarcinoma (EAC), as well as reduced drug delivery and resistance to therapy. However, additional work is needed to elucidate underlying mechanisms of the disease in the context of changes in ECM biomechanics. In my talk, I will first describe the design of an engineered hydrogel as a 3D cancer organoid niche to elucidate the contribution of matrix stiffness on EAC progression. I will then show how we exploited the tunability of our engineered platform to identify potential matrix stiffness-activated therapeutic targets in patient-derived EAC organoids. Importantly, the modular nature of the engineered hydrogel platform allows for potential adaptation to the culture of 3D organoid models of other human diseases.

BIO
Ricardo Cruz-Acuña is an Assistant Professor of Cancer Engineering in the College of Dental Medicine at Columbia University Irving Medical Center. In his lab, Cruz-Acuña focuses on integrating aspects of biomaterial engineering, cell and molecular biology, and 3D organoid biology to (1) understand the contributions of the extracellular matrix properties to tumorigenesis, and (2) identify mechanisms important for epithelial developmental patterning and organogenesis. His work will help elucidate how cancer progresses within a dynamically evolving extracellular matrix that modulates every behavioral facet of the tumor cells, and will reveal novel mechanisms that drive human organ development.

Cruz-Acuña completed his Ph.D. in Bioengineering at the Georgia Institute of Technology under the supervision of Andrés J. García, Ph.D.. Cruz-Acuña then joined the laboratory of Anil K. Rustgi, Ph.D. at University of Pennsylvania and at the Herbert Irving Comprehensive Cancer Center in Columbia University Irving Medical Center for his postdoctoral research training.

In addition to several awards he received during his training, Cruz-Acuña is the recipient of a NIH/NIDDK K01 Research Scientist Development Award (2023). He is a member of the American Association for Cancer Research (AACR) and the Society for Biomaterials (SFB).

 

]]> Colly Mitchell 1 1712086610 2024-04-02 19:36:50 1713957476 2024-04-24 11:17:56 0 0 event "The Role of Matrix Stiffness in Esophageal Cancer: Mechanism to Translational Therapeutics" - Ricardo Cruz-Acuña, Ph.D. - Columbia University Irving Medical Center

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<![CDATA[2024 BioE Day]]> 27195 Presentations from the 2023 BioE Award Winners, featured BioE Alum Seminars, and a Rapid Fire Thesis Competition. Lunch served (while supplies last!).

Open to all Bioengineering Students and Faculty!

AGENDA

9:30 a.m.        Coffee Corner
10:00 a.m.      Outstanding Advisor and Thesis Presentation
11:00 a.m.      Alumni Presentations
12:00 p.m.      Outstanding Paper Presentation and Lunch
12:30 p.m.      Rapid Fire Presentations
2:00 p.m.        Alumni Panel
3:00 p.m.        Awards and Ice Cream - Bioquad
4:30 p.m.        Adjourn


 

]]> Colly Mitchell 1 1713892195 2024-04-23 17:09:55 1713957280 2024-04-24 11:14:40 0 0 event Celebrating the 11th anniversary of IBB's interdisciplinary Bioengineering program.

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2024-05-02T09:30:00-04:00 2024-05-02T16:00:00-04:00 2024-05-02T16:00:00-04:00 2024-05-02 13:30:00 2024-05-02 20:00:00 2024-05-02 20:00:00 2024-05-02T09:30:00-04:00 2024-05-02T16:00:00-04:00 America/New_York America/New_York datetime 2024-05-02 09:30:00 2024-05-02 04:00:00 America/New_York America/New_York datetime <![CDATA[IBB website]]> Divya Bhakta and Spencer Zhang - BioE Day Co-Chairs

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<![CDATA[BioE PhD Proposal Presentation- Valencia Watson]]> 27917 Advisors:

Dr. Cheng Zhu, Ph.D. (BME, Georgia Institute of Technology & Emory)

Committee:

Dr. Edward Botchwey, Ph.D. (BME, Georgia Institute of Technology & Emory)

Dr. Nicole Schmitt, M.D. (Department of Otolaryngology, Emory University)

Dr. Karmella Haynes, Ph.D. (BME, Georgia Institute of Technology & Emory)

Dr. John Blazeck, PhD. (Chemical & Biomolecular Engineering, Georgia Institute of Technology)

 

Mechanisms of impaired T cell antigen sensing in TP53 mutation expressing cancers, and the co-agonist effect of Wild Type (WT) p53 self-antigen

Immunotherapy is becoming increasingly more popular as a treatment option for cancer, especially in patients with chemotherapy resistant tumors. Although immunotherapy has been highly bought into as a treatment option for cancer patients, product efficacy is low. Taking interest in the rising occurrence of head and neck squamous cell carcinoma (HNSCC), consider anti-PD-1 (α-PD1), for example. α-PD1 is an FDA approved ICB treatment for metastatic HNSCC, but a marginal percentage of patients respond to treatment. Immunotherapies such as α-PD1, provide a future in cancer therapy that aims to reduce the toxic side effects of chemotherapy, however, further insight into TME immunosuppression is required to improve the efficacy of these treatment methods.

To advance the knowledge of TME immunosuppression, this study will focus on cytotoxic T cells, as they are integral in tumor clearance. CD8+ T cells are presented antigens in a histocompatibility complex (MHC) manner. The T cell receptor (TCR) forms a bond with the epitope presented in the binding groove of the major histocompatibility complex (pMHC). T cells exert endogenous forces on TCR–pMHC bonds to amplify antigen sensing. To bind pMHC, TCR experiences a conformational change. In the inactive TCR conformation, cholesterol binds the TCRβ subunit to allosterically regulate its function. Manipulation of cholesterol may enhance the anti-tumor immune response of cytotoxic T cells by unknown mechanisms. Recently, our lab demonstrated melanoma TME induces impaired T cell antigen response. We aim to expand these findings to determine if impaired TCR antigen recognition is conserved in other cancer types, test whether targeting cholesterol can restore TCR antigen recognition, and to identify TME immunosuppressive factors that may be contributing to this apparent loss in function. It is hypothesized that reduced TCR antigen response will be seen in other cancer types and can be recovered through cholesterol inhibition.

TCR based precision adoptive cell therapy has also demonstrated potential as a treatment option for cancer patients with tumors expressing tumor suppressor protein TP53 gene mutations. Still, extensively more work needs to be done to better characterize the TCR tumor antigen (neoantigen) response and improve clinical outcomes. We aim to advance the understanding of p53 mutant reactive TCRs and make contributions towards the development of parameters needed to determine their efficacy in ACT. Studies on ACT and other forms of immunotherapy suggest that TCR affinity, force, and downstream signaling are critical for optimal T-cell function and anti-tumor immune responses30.  We aim to explore differences in the affinity, signaling and mechanosensing of 5 patient-derived, R175H hot spot mutant reactive, TCRs to self vs. mutated ligand. We hypothesize that non-stimulatory wild-type (WT) p53 peptide will enhance binding of TCR to antigen via CD8.

]]> Laura Paige 1 1713497894 2024-04-19 03:38:14 1713497990 2024-04-19 03:39:50 0 0 event BioE PhD Proposal Presentation- "Mechanisms of impaired T cell antigen sensing in TP53 mutation expressing cancers, and the co-agonist effect of Wild Type (WT) p53 self-antigen" - Valencia Watson

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<![CDATA[BioE PhD Proposal Presentation- Ana de Pereda]]> 27917 Committee

• Dr. Lily Cheung (Ph.D. Advisor, Chemical Engineering, GT )

• Dr. Hang Lu (Chemical Engineering, GT)

• Dr. Mark Styczynski (Chemical Engineering, GT)

• Dr. John Blazeck (Chemical Engineering, GT)

• Dr. JC Gumbart (Chemistry and Biochemistry, GT)

 

Exploring the Oligomerization of Sugar Transporters for the Advancement in Plant Systems and Synthetic Biology 

Plant SWEET proteins play a pivotal role as sugar transporters, contributing to crucial processes in plants such as reproduction, stress resistance, and sugar distribution. This thesis proposal will investigate the oligomerization of these key membrane transporter proteins, aiming to unravel their complex emergent functions. By understanding these functions, the goal is to pioneer the engineering of sugar transporters with novel capabilities. Employing advanced characterization techniques, including native mass-spectrometry and fluorescence-based assays, this study aims to accurately quantify the stoichiometry of SWEET oligomers in both Arabidopsis thaliana and yeast heterologous expression systems. Furthermore, the research will establish a comprehensive quantitative model to describe sugar transport dynamics for the oligomeric transporters and their individual subunits. Emphasis will be placed on SWEET proteins associated with plant reproduction to create synthetic sugar pumps designed to enhance sugar allocation to endosperm tissues. Through this interdisciplinary approach, the study seeks to delineate the specific impact oligomerization has on sugar transport across plant membranes, thereby informing the intelligent engineering of plant sugar distribution mechanisms for advancements in agricultural productivity and food security. 

 

]]> Laura Paige 1 1713480339 2024-04-18 22:45:39 1713480402 2024-04-18 22:46:42 0 0 event BioE PhD Proposal Presentation- "Exploring the Oligomerization of Sugar Transporters for the Advancement in Plant Systems and Synthetic Biology " - Ana de Pereda

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<![CDATA[BioE PhD Defense Presentation- Tong Yu]]> 27917 Committee Members:

Todd Sulchek, PhD (Advisor)

Sunil Raikar, MD

Gabe Kwong, PhD

James Dahlman, PhD

Wilbur Lam, PhD

A Biomechanics-Based Delivery Strategy To Primary Immune Cells For Generating Cell Therapy With Multiple Gene Knockout

 Abstract: Adaptive T cell therapy has emerged as a promising strategy in cancer treatment, utilizing synthetic receptor modified T cells to specially target tumor antigens. Despite successes, challenges persist, including the need for multiplexed gene editing in production of allogeneic T cell product, expanding application to T cell malignancies, and overcoming T cell dysfunction. These challenges require new technologies that lead to safer and efficient multiplexed gene editing techniques to lead to improved therapies. Currently, multiplexed gene editing is performed in one process step, raising concerns regarding chromosome translocations. This thesis addresses safer and more efficient multiplexed gene editing by leveraging the innovative microfluidic volume exchange for cell transfection (VECT) platform. To achieve efficient and reproducible delivery of gene editing cargo to primary T cells, we propose to understand device and intrinsic cellular attributes that significantly impact delivery outcome. Then, we design optimal devices for sequential gene editing of primary T cells in CAR (Chimeric Antigen Receptor) T engineering pipeline, focusing on the reduction of chromosomal translocation. We hypothesize sequential multiplexed gene editing results in lower chromosomal translocation and improved T cell persistence. This study addresses the goals through 3 aims. Aim 1 focuses on identifying critical design elements (CDEs) for VECT devices, revealing device design and operational factors influencing delivery to primary T cells. Aim 2 demonstrates VECT's capability in functional Cas9 delivery and sequential gene editing of CAR T cells. Aim 3 focuses on intrinsic cell mechanics to reveal cell biomechanics' contributions to delivery efficiency. In completing the study, we created two easy fabrication methods to reproducibly generate high delivery to T cells, Then, we demonstrated an application of VECT to deliver CRISPR/Cas9 to mediate gene editing in T cells. VECT was shown to be capable of generating highly efficient and viable TCR and B2M knockout T cells in both batch and sequential workflow. Importantly, VECT sequential editing is shown to reduce the frequency of chromosomal translocations. Interestingly, we identified a combined effect of strain rate and acceleration to significantly improve delivery; and identified cell stiffness as an intrinsic determinant of delivery efficiency. Overall, this study underscores VECT's potential in industrial-scale multiplexed gene editing of T cells with improved safety profile.

]]> Laura Paige 1 1713479340 2024-04-18 22:29:00 1713479395 2024-04-18 22:29:55 0 0 event BioE PhD Defense Presentation-  "A Biomechanics-Based Delivery Strategy To Primary Immune Cells For Generating Cell Therapy With Multiple Gene Knockout" - Tong Yu

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<![CDATA[BioE PhD Defense Presentation- Mercedes Gonzalez]]> 27917 Advisors:

Dr. Craig Forest (Mechanical Engineering, Georgia Institute of Technology)

Dr. Matthew Rowan (Biological Sciences, Emory University)

 

Committee Members:

Dr. Annabelle Singer (Biomedical Engineering, Georgia Institute of Technology)

Dr. Bilal Haider (Biomedical Engineering, Georgia Institute of Technology)

Dr. Christopher Rozell (Electrical and Computer Engineering, Georgia Institute of Technology)

 

Automated cellular electrophysiology to investigate the role of interneurons in Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disease, accounting for about two thirds of dementia cases. Despite significant efforts to diagnose and cure AD there are still no effective therapeutics to halt disease progression. While the conventional understanding attributes memory loss to the buildup of amyloid and tau proteins, emerging evidence suggests that cognitive decline in AD may stem from neuronal circuit dysregulation rather than protein aggregation. Specifically, alterations in the excitability of inhibitory interneurons may contribute to circuit dysfunction, although the evolution of this dysregulation across brain regions and over time remains poorly understood. To address this gap, this thesis systematically investigated the emergence of parvalbumin interneuron dysfunction in AD, confirming their early involvement in vulnerable brain regions.

 

To study these PV interneurons at the single cell level, with sufficient spatial and temporal resolution, this thesis will utilize patch clamp electrophysiology. The patch clamp technique is remains necessary for fully elucidating cell-type-specific behavior, although it is difficult and time-intensive. While patch clamp systems have emerged that automate certain aspects of the procedure, there remain challenges that can be remedied with improved automation techniques. To overcome these obstacles, several strategies have been developed to improve the whole-cell success rates and facilitate the execution of automated, high-throughput investigations. In the initial identification of cells within acute brain slices, a deep learning methodology automatically nominate neurons for subsequent automated experiments. Addressing concerns regarding pipette localization errors, a convolutional neural network, specifically ResNet101, has been adapted and trained to autonomously detect and rectify the misplacement of pipette tips during automated in vitro patch clamp experiments. Furthermore, to facilitate investigations into synaptic connections between neurons, a method named patch-walking was demonstrated in brain slices, enabling efficient finding of synaptic connections.

]]> Laura Paige 1 1713479158 2024-04-18 22:25:58 1713479226 2024-04-18 22:27:06 0 0 event BioE PhD Defense Presentation- "Automated cellular electrophysiology to investigate the role of interneurons in Alzheimer’s disease" - Mercedes Gonzalez

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<![CDATA[BioE PhD Proposal Presentation- Hyoann Choi]]> 27917 https://gatech.zoom.us/j/98694357299?pwd=MnYxbDRtamw2Tzhrd05RTG9tdiszZz09&from

 

Committee

Dr. Wilbur Lam (Ph.D. Advisor, Biomedical Engineering, GT & Emory)

Dr. Anant Madabhushi (Biomedical Engineering, GT & Emory)

Dr. Paynabar Kamran (Industrial & Systems Engineering, GT)

Dr. Eva Dyer (Electrical and Computer Engineering, GT)

Dr. David Myers (Biomedical Engineering, GT & Emory)

 

Unraveling Hidden Heterogeneity: Quantitative Characterization of Cellular Heterogeneity

in Multicolor Flow Cytometry Data for Enhanced Insights

Varying health outcomes present a significant challenge in medicine. At the biological and microscopic level of human health, cells are the smallest functional with diverse functions, undergoing dynamic changes over time and exhibiting unique variations among individuals.

Understanding this intra- and inter-individual cellular diversity, and its impact on health is crucial for the implementation of personalized medicine. Multicolor flow cytometry is the most established single-cell technology, providing multi-parametric information about each cell's protein profiles. It has facilitated the discovery of cellular subpopulations and biomarkers for health and disease. However, current analyses of multicolor flow cytometry data fail to fully

capture multifaceted representations of cellular heterogeneity. The focus on population averages and frequencies neglects the amount, shape, and direction of cellular heterogeneity, which may collectively indicate various forms of cellular heterogeneity with biological and clinical significance. Yet, the lack of quantitative definitions for these aspects hinders objective analyses of their contribution to health. This research proposes and evaluates quantitative metrics to capture previously under-appreciated aspects of cellular heterogeneity in multicolor flow cytometry data. It first examines the biological significance of cellular heterogeneity in healthy platelets, elucidating its translation into functional diversity at the population-level in hemostasis and thrombosis. Subsequently, it investigates the clinical relevance of cellular heterogeneity in peripheral blood mononuclear cells (PBMCs) to understand the role of immune cell heterogeneity in the manifestations of long COVID. By providing a new quantitative lens to uncover hidden aspects of cellular heterogeneity, the proposed methods offer a more holistic understanding of cellular variability. Serving as biomarkers to establish the reference of homeostatic forms of cellular heterogeneity, the proposed metrics can be used to diagnose and monitor diseases and guide the design of tailored therapies. Ultimately, these metrics reveal “hidden heterogeneity”, which will help better resolve and manage inter-individual differences in disease manifestations and therapy responses, advancing personalized medicine.

]]> Laura Paige 1 1712671471 2024-04-09 14:04:31 1712671538 2024-04-09 14:05:38 0 0 event BioE PhD Proposal Presentation- "Unraveling Hidden Heterogeneity: Quantitative Characterization of Cellular Heterogeneity in Multicolor Flow Cytometry Data for Enhanced Insights" - Hyoann Choi

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<![CDATA[BioE PhD Defense Presentation- Nischita Kaza]]> 27917 Advisor:

Francisco E. Robles, Ph.D. (Georgia Institute of Technology and Emory University) 

Committee Members:  

Ahmet F. Coskun, Ph.D. (Georgia Institute of Technology and Emory University School of Medicine)   

Peng Qiu, Ph.D. (Georgia Institute of Technology and Emory University)  

Thomas K. Gaylord, Ph.D. (Georgia Institute of Technology)   

Wilbur A. Lam, M.D., Ph.D. (Georgia Institute of Technology and Emory University School of Medicine)   

 

Label-free Deep-Ultraviolet Microscopy: Accessible Molecular Imaging from Bench to Point of Care

Imaging with ultraviolet (UV) light (~ 200 - 400 nm) enables label-free molecular imaging due to the distinctive absorption and dispersion properties of several physiologically important, endogenous biomolecules in this spectral region. In addition, the shorter wavelength of UV light offers higher spatial resolution than conventional imaging systems that use visible light. Furthermore, advances in UV light sources and detectors have resulted in setups that enable contiguous imaging of live cells over long durations without significant photodamage.

This work aims to enhance the capabilities of deep-UV microscopy for accessible imaging of biological samples. Initially, we introduce a simple hyperspectral UV microscopy technique to extract quantitative absorption information from biological samples without prior knowledge of their optical properties. Following this, we employ multi-spectral deep-UV microscopy to quantify hemoglobin in red blood cells. Subsequently, we leverage recent advances in deep learning to develop an automated pipeline for label-free hematology analysis using single-wavelength UV microscopy images. In conjunction with a compact deep-UV microscope and custom microfluidic devices, this work can enable low-cost, efficient, and label-free hematology analysis within minutes, suitable for clinical, at-home, or low-resource settings. Additionally, we explore the development of a multispectral UV microscope for high-resolution, 3D tomographic imaging of cells.

Overall, this dissertation advances UV microscopy through improved instrumentation, analysis, and computational reconstruction, establishing it as an effective and economical label-free imaging tool for research, clinical, and point-of-care applications. We anticipate that the high-resolution molecular and structural information obtained from UV microscopy will further our understanding of fundamental biology and aid in disease diagnosis, monitoring, and treatment planning.

]]> Laura Paige 1 1712671336 2024-04-09 14:02:16 1712671356 2024-04-09 14:02:36 0 0 event BioE PhD Defense Presentation- "Label-free Deep-Ultraviolet Microscopy: Accessible Molecular Imaging from Bench to Point of Care"  -Nischita Kaza

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<![CDATA[BioE PhD Defense Presentation- Carla Kumbale]]> 27917 Committee:

Eberhard O. Voit, Ph.D. (Ph.D. Advisor) (Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech and Emory University; Department of Biological Sciences, University of Texas at Dallas)

Qiang Zhang, M.D., Ph.D. (Co-Advisor) (Gangarosa Department of Environmental Health, School of Public Health, Emory University)

Dr. Melissa L. Kemp, Ph.D. (Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University)

Peng Qiu, Ph.D. (Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University)

Mark Styczynski, Ph.D. (School of Chemical and Biomolecular Engineering, Georgia Institute of Technology)

 

Assessing the Impact of Dioxin on Human Health through Mathematical Modeling

Biological systems are organized in distinct but connected layers, which makes their analysis a challenge. The higher layers usually correspond to a “big picture” of a physiological event, whereas the lower levels account for increasing granularity and detail. It is infeasible to carry along all details from lower levels, partly for technical reasons, but also because they would overwhelm insights at the higher level due to their sheer numbers and the fact that they typically run on much faster time scales.

              This work addresses the well-known challenge of biomedical multiscale analysis with a novel adaptation of the Template-and-Anchor (T&A) modeling paradigm. It considers a template as a high-level, coarse-grained model that focuses exclusively on the main physiological components of a system and involves correspondingly few variables, processes and parameters. The template contains as variables the anchor models, which are modules of component sub-systems that provide more elaborate descriptions of specific biological details. This conceptual framework does not attempt to capture simultaneously all details within a single computable structure as many other multiscale models do. Instead, the often-overwhelming multilevel task is dissected into smaller, stand-alone models that are analyzed separately. This new adaptation of the T&A approach offers substantial advantages without losing resolution. First, the divide-and-conquer method enhances computational efficiency. Second, unlike other methods, each anchor is analyzed individually, producing a record of crucial input-output relationships that are ultimately used in the template model. Third, anchor models can be replaced with alternative representations without affecting the structure of the template or other anchors. Fourth, the T&A model provides flexible guidelines for its setup and for defining variables across scales. 

Using the T&A approach, this work addresses the health implications of exposure to dioxin (specifically, 2,3,7,8-tetrachlorodibenzo-p-dioxin), a persistent organic pollutant which can severely affect health, depending on the magnitude of exposure. The template captures the overall effects of dioxin on the dynamics of cholesterol, a prominent target of dioxin. The anchor models serving as variables in the overall template model include hepatic cholesterol biosynthesis (via the mevalonate pathway), lipoprotein metabolism, and estrogen synthesis. The creation and combination of anchor and template models enables a holistic evaluation of the impact of dioxin, which can be translated into a tool for comprehensive computational health risk assessments.

              On the theoretical side, this work discerns fundamental differences in the conceptual set-up of templates and anchors which may be viewed as dual structures of each other, as the variables in anchor models are material quantities, whereas the variables in template models are processes. T&A modeling, and multiscale modeling in general, hold promise for a deeper understanding of complex systems and for advancing personalized medicine and risk assessment, interspecies translation, and the development of virtual clinical trials.

]]> Laura Paige 1 1711976499 2024-04-01 13:01:39 1712612548 2024-04-08 21:42:28 0 0 event BioE PhD Defense Presentation- "Assessing the Impact of Dioxin on Human Health through Mathematical Modeling" - Carla Kumbale

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<![CDATA[BioE PhD Defense Presentation- Jihoon Lee]]> 27917 Advisor: Shuichi Takayama, PhD (Georgia Institute of Technology)

 

Committee Members:
Stanislav Emelianov, PhD (Georgia Institute of Technology)

M. G. Finn, PhD (Georgia Institute of Technology)

Eric J. Sorscher, MD (Emory University School of Medicine)

Jason R. Spence, PhD (University of Michigan)

 

Human Airway Organoids with Reversed Biopolarity: Implications for Infectious Disease, Drug Discovery, and Pathophysiology

Organoid research is exploring a new niche: apical-out organoids. These engineered structures, characterised by their outward-facing apical membrane, offer unique and exciting avenues for research. This dissertation introduces human airway organoids with reversed polarity (AORBs) and demonstrates their potential in studying infectious diseases, drug discovery, and pathophysiology, with a specific focus on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and bronchiolitis obliterans syndrome (BOS). First, we successfully established a robust and optimised standard operating procedure (SOP) for generating AORBs from human primary upper airway epithelial cells, building upon a previously described minimal extracellular matrix (ECM) scaffolding method. The resulting AORBs were cultured free-floating in a high-throughput, single-organoid-per-well format. Single-cell RNA sequencing confirmed the in vivo-like cellular heterogeneity of AORBs, validating their close resemblance to natural airway physiology. Next, we demonstrated the utility of AORBs as a platform for SARS-CoV-2 infection and antiviral drug screening. AORBs supported efficient infection by five SARS-CoV-2 variants, while enabling high-throughput screening, effectively identifying false negatives and false positives. Furthermore, the SOP was refined to develop a tri-culture organoid model, integrating airway epithelial cells, fibroblasts, and peripheral blood stem cells, with the objective of addressing the lack of a human model and the limited translatability of existing animal models in studying BOS pathogenesis. By manipulating human leukocyte antigen matching between epithelial and immune cells in vitro, our BOS model can closely recapitulate the clinical condition, facilitating mechanistic studies and therapeutic discovery. Overall, this dissertation establishes AORBs as a versatile and standardised platform for investigating infectious diseases, drug discovery, and pathophysiology of the respiratory system. The standardisation capacity of the developed SOP holds broader implications for standardising organoids, aligning with the recently updated FDA regulation lifting the mandate for animal studies on therapeutic testing.

]]> Laura Paige 1 1711977771 2024-04-01 13:22:51 1711977824 2024-04-01 13:23:44 0 0 event BioE PhD Defense Presentation-  "Human Airway Organoids with Reversed Biopolarity: Implications for Infectious Disease, Drug Discovery, and Pathophysiology" - Jihoon Lee

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<![CDATA[BioEngineering Graduate Committee Meeting]]> 27917 The BioEngineering graduate committee will meet to review/approve program policies, program faculty applications and submitted student petitions.

]]> Laura Paige 1 1611673260 2021-01-26 15:01:00 1711976666 2024-04-01 13:04:26 0 0 event BioEngineering Graduate Committee Meeting

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<![CDATA[BioE PhD Proposal Presentation- Rajas Poorna]]> 27917 Advisors:

Saad Bhamla, Ph.D. (ChBE, Georgia Institute of Technology)

Marcus Cicerone, Ph.D. (Chemistry & Biochemistry, Georgia Institute of Technology)

Committee:

Nicholas Hud, Ph.D. (Chemistry & Biochemistry, Georgia Institute of Technology)

Mark Prausnitz, Ph.D. (ChBE, Georgia Institute of Technology)

Francisco E Robles, Ph.D. (BME, Georgia Institute of Technology)

 

Bringing Universal Diagnostics to the Point-of-Care: Raman Spectroscopy, Sample Preservation, and Machine Learning

Raman spectroscopy (RS) of biofluids such as blood serum, urine, and saliva can diagnose a wide range of diseases such as diabetes, malaria, tuberculosis, celiac disease, cancer, and Alzheimer's. This has been shown on conventional Raman spectrometers costing >$100,000. We are developing a sub-$100 “frugal” Raman spectrometer with comparable sensitivity for broad-based biofluid diagnostics at the point-of-care (POC). We predict that our method will have sufficient signal for many diagnostics in just a 3-minute scan. Unlike Surface Enhanced Raman Spectroscopy (RS), our technique requires no special reagents, allowing the cost per test to drop to almost zero. We will first target tuberculosis (TB), for which such a fast, affordable test, deployed at TB centers, can save nearly 200,000 lives per year by reducing patient loss to follow-up.

In parallel, we are developing a fast, sub-$100 POC sample-drying instrument that enables biofluids to be preserved and transported without a cold-chain. This will enable remote POCs to offer a wider array of diagnostic tests without forcing the patient to travel. Our $60 prototype can dry a 1 mL sample in under 20 minutes where the Labconco Centrivap, a >$20,000 commercial instrument, takes over 5 hours (18x faster).

Finally, we have developed two machine learning techniques for analyzing the metabolomic cell state in Raman microscopy images. We use these to show that Raman microscopy can potentially identify the state of live cells to comparable or better resolution than transcriptomics. One of the techniques, SampleMAP, is of interest to the wider data science community as a dimensionality reduction technique with a significantly enhanced ability to identify clusters in data compared to UMAP.

]]> Laura Paige 1 1710941899 2024-03-20 13:38:19 1710941899 2024-03-20 13:38:19 0 0 event BioE PhD Proposal Presentation- "Bringing Universal Diagnostics to the Point-of-Care: Raman Spectroscopy, Sample Preservation, and Machine Learning" -Rajas Poorna

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<![CDATA[BioE PhD Proposal Presentation- Zikai Yu]]> 27917 Thesis Advisor:
Prof. Hang Lu (School of Chemical and Biomolecular Engineering, Georgia Tech)

Committee Members:
Prof. Mark Styczynski (School of Chemical and Biomolecular Engineering, Georgia Tech)
Prof. Patrick McGrath (School of Biological Sciences, Georgia Tech)
Prof. Todd Sulchek (School of Mechanical Engineering, Georgia Tech)
Prof. Eva Dyer (School of Biomedical Engineering, Georgia Tech)

Automated pipeline for building whole-brain anatomical atlases and comparative analysis of diverse biological factors in C. elegans

 

Abstract
The roundworm C. elegans offers a unique opportunity as a model organism to develop necessary methodologies for studying head anatomy. Existing approaches, while providing valuable insights, have technical limitations in terms of accuracy, throughput, robustness, and accessibility. This proposal introduces an optimized pipeline to overcome these challenges and explore its application across diverse scenarios. In aim 1, an experimental and computational pipeline will be presented for constructing complete whole-brain data-driven anatomical atlases for N2 young adult worms. In Aim 2, the pipeline will be adapted for comparative studies across various biological factors such as genetic backgrounds and developmental stages, with carefully chosen metrics to understand underlying biology from observed differences. In Aim 3, our standard N2 atlas will be incorporated to address challenges in functional imaging analysis, accompanied by advancements in image processing techniques. This proposed pipeline has the potential to enhance our understanding of C. elegans brain and may contribute to a broader comprehension of nervous systems in other biological organisms.

]]> Laura Paige 1 1710424258 2024-03-14 13:50:58 1710424258 2024-03-14 13:50:58 0 0 event BioE PhD Proposal Presentation- "Automated pipeline for building whole-brain anatomical atlases and comparative analysis of diverse biological factors in C. elegans" -Zikai Yu

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<![CDATA[BioE PhD Defense Presentation- Samuel Waters]]> 27917 Advisor: Gari Clifford, DPhill – School of Biomedical Engineering, GT

 

Committee:

Eva Dyer, PhD – School of Biomedical Engineering, GT

Thad Starnder, PhD – School of Electrical & Computer Engineering, GT

Hua Wang, PhD – Department of Information Technology, ETH Zürich

Reza Sameni, PhD – Department of Bioinformatics, Emory

 

METHODS FOR GENERALIZED LOW-DIMENSIONAL EEG ANALYSIS
USING TRANSFER LEARNING

Polysomnography (PSG) is a widely used procedure for diagnosing sleep disorders such as narcolepsy and sleep apnea, however its invasive and time-consuming nature make it infeasible for any form of long-term monitoring. It requires patients to sleep in a hospital setting for several nights while their EEG and other vitals are continuously recorded, after which a trained human clinician must manually score every 30-second block in the entire recording. Long-term monitoring of treatment effectiveness or disease progression thus needs to be conducted using less reliable methods such as wrist actigraphy, sleep diaries, or subjective surveys of sleep quality. The lack of effective methods for long-term monitoring is also problematic for longitudinal studies examining the interaction between sleep quality and other pathologies such as Alzheimer's. There is thus considerable interest in automated sleep staging using at-home wearable sensors. 

A problem in developing automated sleep staging algorithms however is the lack of data available for wearable sensors. There is plenty of data available for in-hospital PSG, but very little for wearable sensors, as they aren't normally used in clinical practice. A possible solution however is the use of transfer learning - a method of boosting machine learning performance on one task using data from a similar task. 

In this thesis, we use transfer learning to make several advances in the field of sleep staging with wearable sensors: 1) We test a variety of transfer learning techniques under a variety of conditions and neural network architectures to determine which transfer learning method is most effective. 2) We develop a novel transfer learning algorithm augmenting training data with synthetic EEG generated using electrophysiological models designed to output data resembling that of the targeted wearable sensor. 3) We used transfer learning to develop a sleep staging model specifically designed for use on mild cognitive impairment patients which is far more effective than models trained on healthy subjects. 4) We used transfer learning to automate sleep staging with an experimental in-ear wearable which is far more comfortable and user-friendly than scalp wearables yet achieves superior sleep staging performance to some commercially available scalp wearables. 

]]> Laura Paige 1 1701363638 2023-11-30 17:00:38 1701363638 2023-11-30 17:00:38 0 0 event BioE PhD Defense Presentation-  " METHODS FOR GENERALIZED LOW-DIMENSIONAL EEG ANALYSIS USING TRANSFER LEARNING" -Samuel Waters

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<![CDATA[BioE PhD Defense Presentation- Rachel Ringquist]]> 27917 Advisor: Dr. Krishnendu Roy (Engineering, Vanderbilt) 

 

Committee: 

Dr. Ankur Singh (School of Mechanical Engineering, Georgia Tech)

Dr. Ahmet Coskun (School of Biomedical Engineering, Georgia Tech)

Dr. Hang Lu (School of Chemical and Biomolecular Engineering, Georgia Tech)

Dr. Rabin Tirouvanziam (Department of Pediatric Infectious Diseases, Emory)

 

An immune-competent microvascularized human lung-on-chip device for studying immunopathologies of the lung

 

      Severe influenza affects 3-5 million people worldwide each year, resulting in >300,000 deaths. Standard-of-care antiviral therapeutics have limited effectiveness in these patients where infection severity is driven by an aberrant immune response. In severe influenza, the hyperactive immune system causes acute cytokine storm, cytopenia, and local tissue damage. Current preclinical models of severe influenza, in small animal models and in vitro, fail to recapitulate the human immune response to severe viral infection accurately. Here, we bioengineered a human lung tissue model that represents small airway structures with tissue-resident and circulatory immune cells. The immune-competent lung tissue model comprises of a 3D, perfusable microvascular network underneath a mature, differentiated epithelium at an air-liquid interface.

      With this model, we demonstrate that a conventional lung-on-chip (LOC) that lacks immune cells induces limited cytokine response to severe influenza infection, and while a LOC with tissue-resident macrophages induces significant response in the airway, the presence of both tissue-resident and circulatory immune cells was necessary to elicit a significant airway and interstitial cytokine storm. We demonstrate through extensive microscopy, secretome, and single-cell RNA sequencing analyses that severe flu infection results in significant lymphopenia, extracellular matrix remodeling, and transcriptional shutdown in fully immune-competent lung tissues. Lastly, we highlight the prominent role of stromal-immune interactions in the response to severe influenza infection, with stromal cells participating in both cytokine signaling and ECM remodeling. The introduction of both tissue-resident and circulatory immune cells into this lung-on-chip model allows for investigation into the distinct role of each immune cell type in the initiation and progression of influenza and may shed light on potential therapeutic avenues targeting immune dysregulation.

]]> Laura Paige 1 1701304977 2023-11-30 00:42:57 1701304977 2023-11-30 00:42:57 0 0 event BioE PhD Defense Presentation- "An immune-competent microvascularized human lung-on-chip device for studying immunopathologies of the lung" - Rachel Ringquist

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<![CDATA[BioE PhD Defense Presentation- Bryan Wang]]> 27917 Advisor: Krishnendu Roy, PhD – School of Biomedical Engineering, GT

 

Committee:

Stephen Balakirsky, PhD – Georgia Tech Research Institute

Fani Bukouvala, PhD – School of Chemical and Biomolecular Engineering, GT

Johnna Temenoff, PhD – School of Biomedical Engineering, GT

Carolyn Yeago, PhD – Institute of Bioengineering and Bioscience, GT

 

 

 

 

Process Development and Process Analytical Technology Integration for Cell Therapy Manufacturing

 

Biomanufacturing of cell therapies involves highly complex and labor-intensive processes, where the process parameters and biological variabilities can significantly influence product quality, reproducibility, and therapeutic efficacy of the products. The complexity and largely manual unit operations contribute to product variability and high cost. To address these manufacturing challenges, we designed a digital-twin-enabled closed-loop cell manufacturing platform with automation and feedback controls. This platform integrates process analytical technologies (PAT) to enable deeper process understanding and provide real-time control of process variables. Specifically, we designed bench-scale bioreactors with automated sampling, at-line and in-line monitoring, digital twin-enabled media nutrients estimation, and feedback-controlled feeding capabilities. Human umbilical cord tissue-derived MSCs (CT-MSCs) and T cells were used as the example cell therapy product. At-line glucose and lactate monitoring confirmed the accuracy of the digital twin estimations. Spent media samples and detailed functional characterizations of the MSCs and T cells end-products generated from the automation-controlled bioreactor demonstrated that high expansion and functions of the MSCs and T cells were maintained in these closed-loop bioreactors. Real-time imaging with quantitative oblique back illumination microscopy showed high-resolution images of cells in-process in a dynamic 3D environment. Overall, the digital twin-enabled bioreactor platform reduced costs, labor, time, and, more importantly, perturbations; and could improve yield while maintaining the phenotype and quality of cell therapy products. Our integrated automation system provides a blueprint for multiplexed PAT integration, process optimization, feedback-controlled intelligent automation to enable the discovery, monitoring, and control of critical quality attributes and critical process parameters for cell therapy manufacturing.

]]> Laura Paige 1 1700577403 2023-11-21 14:36:43 1700577403 2023-11-21 14:36:43 0 0 event BioE PhD Defense Presentation- "Process Development and Process Analytical Technology Integration for Cell Therapy Manufacturing" - Bryan Wang

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<![CDATA[BioE PhD Defense Presentation- Thomas Pho]]> 27917 Advisor: Julie Champion, Ph.D. (Chemical and Biomolecular Engineering)

 

Committee Members:

Jennifer E. Curtis, Ph.D. (Physics)

James E. Dahlman, Ph.D. (Biomedical Engineering)

Ravi S. Kane, Ph.D. (Chemical and Biomolecular Engineering)

Mark Prausnitz, Ph.D. (Chemical and Biomolecular Engineering) 

 

 

 

Surface Engineering of Protein Nanoparticles for Intranasal Vaccination

 

Intranasal delivery of vaccines offers a promising alternative approach to invasive intramuscular injection, with additional benefits such as inducing mucosal antibodies and cellular responses to neutralize pathogens before entering systemic circulation. However, nasal secretions and mucosa are biological barriers that have been shown to inhibit the delivery of antigens and nanoparticles to nasal-associated lymphoid tissue (NALT) and lungs. Protein nanoparticles are composed of proteins at high mass-to-carrier ratio, while allowing for biocompatibility and tunable physiochemical properties. They have been demonstrated to be effective vaccines and drug delivery carriers. The surfaces of these carriers can be decorated with coatings and chemical modifications, which can alter transport and immune responses due to their interaction with biological barriers and cells. In this work, we evaluate intranasal localization of engineered surface-coated protein nanoparticles and assess their immune response following vaccination in murine models. To understand the principles behind modifying nanoparticle surface formulations will assist in improving accessibility to the NALT and delivery of protein-based nanocarriers for non-vaccine intranasal delivery. We screened ovalbumin nanoparticles coated with polyethylene glycol (PEG) and layer-by-layer coating of trimethyl chitosan and CpG oligodeoxynucleotide adjuvants delivered intranasally in murine models and compared to unmodified protein nanoparticles. The localization and biodistribution were observed using non-invasive in vivo imaging and for regional localization and tissues using both flow cytometry and immunohistochemistry. Surface-coated nanoparticles were used for intranasal vaccination in a murine model and characterized for the mucosal antigen-specific response, as well as systemic humoral and cellular responses through antibody titers and T-cell activation. The findings and designs from screening coatings with model ovalbumin nanoparticles were incorporated into influenza antigen nanoparticle formulations.  Two influenza antigens (hemagglutinin and matrix protein 2 - (A/California/07/2009(H1N1)) were used to construct a subunit protein nanoparticle vaccine with surface structure control using bioconjugation. A layer-by-layer (LBL) coating approach was used to survey specific formulation based on their administration route. Overall, our findings indicated that LBL surface formulation improved nasal biodistribution and immune response upon intranasal delivery, highlighting a new nanoparticle formulation for nasal vaccines. 

]]> Laura Paige 1 1700577216 2023-11-21 14:33:36 1700577216 2023-11-21 14:33:36 0 0 event BioE PhD Defense Presentation- "Surface Engineering of Protein Nanoparticles for Intranasal Vaccination" - Thomas Pho

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<![CDATA[BioE PhD Defense Presentation- Alex Beach]]> 27917 Advisor:

Dr. Krishnendu Roy (Engineering, Vanderbilt University)

 

Committee Members:

Dr. Andres García (ME, Georgia Institute of Technology)

Dr. Erik Dreaden (BME, Georgia Institute of Technology)

Dr. Valeria Milam (MSE, Georgia Institute of Technology)

Dr. Susan M. Thomas (ME, Georgia Institute of Technology)

 

Utilizing Combinatory Adjuvant-Loaded Chitosan-Derived Nanoparticles for a Joint SARS-CoV-2/Influenza Vaccine

In the wake of the SARS-CoV-2 pandemic and the need for yearly vaccination for flu, there is an ever-growing demand for a single vaccine formulation that can target and immunize against both pathogens. While investigation is ongoing for joint vaccine candidates, the current focus has been mainly on the simultaneous administration of separate vaccines rather than a new hybrid vaccine design. In this work, we have designed and synthesized chitosan and chitosan-IAA-based nanoparticles to use as a platform for combinatorial delivery of multiple vaccine-adjuvants together with soluble delivery of flu and SARS-CoV-2 antigens. Specifically, we have used a combination of the TLR9 agonist CpG and the RLR agonist pUUC. In vitro testing in two distinct primary bone-marrow-derived antigen-presenting cell (APC) cultures demonstrated a strong cell-phenotype-dependent cytokine response to these nanoparticle systems. After administering these with SARS-CoV-2 and H5N1 influenza antigens in a dual-vaccine formulation, we confirmed high pathogen-specific antibody titers in serum and BAL fluid. Our results provide further insights into the impact of immune cell phenotype on vaccine responses and show promise for creating a novel joint subunit vaccine for two prevalent pathogens.

]]> Laura Paige 1 1700577030 2023-11-21 14:30:30 1700577030 2023-11-21 14:30:30 0 0 event BioE PhD Defense Presentation- "Utilizing Combinatory Adjuvant-Loaded Chitosan-Derived Nanoparticles for a Joint SARS-CoV-2/Influenza Vaccine" - Alex Beach

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<![CDATA[BioE PhD Defense Presentation- Sanchita Bhat]]> 27917 Advisor:   

Lakshmi Prasad Dasi, Ph.D. (Georgia Institute of Technology)  


 

Committee:  

Ajit P. Yoganathan, Ph.D. (Georgia Institute of Technology)  

Christopher Breuer, M.D. (Nationwide Children’s Hospital)  

Rudolph Gleason, Ph.D. (Georgia Institute of Technology)  

Scott Hollister, Ph.D. (Georgia Institute of Technology)  

  

Development and Biomechanical Assessment of Heart Valve Replacements Designed for In Utero Deployment 

 

      Congenital heart diseases (CHDs) account for nearly one third of all congenital defects. Patients born with complex congenital cardiac anomalies often require heart valve replacements in their lifetimes. Prenatally, attempts have been made to restore biventricular healthy anatomy in utero by balloon valvuloplasty. A lot of patients that undergo this procedure develop re-atresia or re-stenosis, requiring valve replacements. There has been an investigation into providing a permanent solution to heart valve replacements in children using tissue engineering. 'Neo-tissue' develops using the patient’s own cells, and therefore eradicates the susceptibility of severe rejection possessing the ability to grow, repair and remodel. Tissue engineering can be used as a viable tool in the fetal population due to the high regenerative capacity. This study developed a fetal transcatheter pulmonary valve replacement. The overall hypothesis is that improved understanding of the biomechanics of manufacturing and testing of biodegradable materials can help engineer fetal sized tissue engineered heart valves (TEHVs) and guide future transcatheter device interventions

 

      Specific Aim 1 shed light on the stress distributions and stent characteristics of candidate stent designs simulated with four candidate materials (metal and polymeric).  Results showed differences in stress distributions and stent performance metrics (dog boning, foreshortening and recoil) in the three designs. Both metals performed favorably, although polymer performance (due to high elastic modulus) was better suited to current designs. It was also shown that design had a great effect on distribution of high stresses and composite materials need to be explored in the future to combine the advantages of both metals and polymers. Specific Aim 2 developed and tested alternative sutureless valve assembly techniques that can overcome potential premature failure of valves and benchtop tested patterns of leaflet degradation. Results showed that changing the material density in the valve assembly can help control degradation and performance of the valve in vivo. Specific Aim 3 looked at fetal valve hemodynamic performance and downstream fluid profiles in a pulse duplicator and durability in an AWT. Results showed that although performance values differ between prototypes, all performed well individually and durability in a non-degrading medium was high, indicating the possible longevity of valve in vivo. 

 

      The development of such a TEHV will eliminate the need for repeat interventions and serve as a permanent alternative. Given the few durable options for pediatric patients, this study will improve the feasibility of developing such a device right from the manufacturing to the testing stage. This critical integration of heart valve and tissue engineering may be the first step to the solution that is needed to reverse ventricular hypoplasia and eliminate single ventricle anomalies.

]]> Laura Paige 1 1698757388 2023-10-31 13:03:08 1698757388 2023-10-31 13:03:08 0 0 event BioE PhD Defense Presentation- "Development and Biomechanical Assessment of Heart Valve Replacements Designed for In Utero Deployment " -Sanchita Bhat

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2023-11-13T13:30:00-05:00 2023-11-13T15:30:00-05:00 2023-11-13T15:30:00-05:00 2023-11-13 18:30:00 2023-11-13 20:30:00 2023-11-13 20:30:00 2023-11-13T13:30:00-05:00 2023-11-13T15:30:00-05:00 America/New_York America/New_York datetime 2023-11-13 01:30:00 2023-11-13 03:30:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Proposal Presentation-Josiah Rudge]]> 27917 Advisor:

Aniruddh Sarkar, Ph.D. (Georgia Institute of Technology)

 

Commitee:

John Blazeck, Ph.D. (Georgia Institute of Technology)

Gabe Kwong, Ph.D. (Georgia Institute of Technology)

David Myers, Ph.D. (Georgia Institute of Technology)

Fatih Sarioglu, Ph.D. (Georgia Institute of Technology)

 

Single-Cell Impedance Cytometry Enabling Novel Single-Cell Electroporation Capabilities in a High Throughput Device

 

Cell therapies have shown great promise in treating diseases such as CAR-T cells for blood cancers. Manufacturing these therapies presents considerable challenges and costs. These include quality of donor source material, transfection of cells, and controlling and measuring the quality of the product. Current therapies often transfect cells by viral vectors which are costly, have payload limitations, are difficult to target specific cells with, and present safety concerns due to immunogenicity and oncogenicity. The objective of this thesis is to create a microfluidic single-cell electroporation device and scheme that addresses these cell manufacturing concerns. Electroporation is an alternative non-viral method of transfection that is inexpensive and non-immunogenic. Additionally, it is applicable to different cell types or delivery payloads including larger payloads (e.g. CRISPR-Cas). However, electroporation can cause significant cell death, toxicity, and/or low delivery efficiencies. Here we propose to build a microfluidic device which will electronically measure properties of single cells and apply an electroporation voltage based on that measurement. This feedback can reduce cell death by tailoring the electroporation voltage for each cell. The impedance measurement itself can be used to characterize the quality of cells or distinguish between cell subtypes, all of which can alter electroporation parameters if desired. We propose to use this to develop a scheme for targeted or selective electroporation of specific cells from mixtures. We also propose scale up cell throughput to produce clinically relevant quantities of cells. Finally, we intend to verify the use of this scheme to make CAR-T cells and verify their function using in-vitro assays.

]]> Laura Paige 1 1698757091 2023-10-31 12:58:11 1698757091 2023-10-31 12:58:11 0 0 event BioE PhD Proposal Presentation- "Single-Cell Impedance Cytometry Enabling Novel Single-Cell Electroporation Capabilities in a High Throughput Device" Josiah Rudge

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2023-11-14T09:00:00-05:00 2023-11-14T11:00:00-05:00 2023-11-14T11:00:00-05:00 2023-11-14 14:00:00 2023-11-14 16:00:00 2023-11-14 16:00:00 2023-11-14T09:00:00-05:00 2023-11-14T11:00:00-05:00 America/New_York America/New_York datetime 2023-11-14 09:00:00 2023-11-14 11:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Defense Presentation- Nathan Zavanelli]]> 27917 Advisor: Woonhong Yeo, Ph.D. (Mechanical and Biomedical Engineering) 

  

Committee Members: 

Todd Sulchek, Ph.D. (Mechanical Engineering) 

Rudolph Gleason , Ph.D. (Mechanical Engineering) 

Omer Inan, Ph.D. (Electrical and Computer Engineering) 

Pamela Bhatti, Ph.D. (Electrical and Computer Engineering) 

  

A Skin-like Sternal Patch to Monitor Autonomic Tone During Cognitive Stress and Sympathetic Arousals in Disordered Sleep

 

The central focus of this thesis is the development of skin-like wearable electronics and sensors that seamlessly integrate with the human body and provide hospital quality physiological monitoring and diagnostics in a simple, minimally obtrusive platform. One of the most poignant tragedies in modern medicine is that many pathologies with highly effective treatments remain undiagnosed, especially in marginalized communities. This suffering is fueled by a systemic failure in current diagnostics techniques: one the one hand, hospital grade in lab tests are expensive, low throughput, and ill-suited for continuous monitoring; on the other, wearable electronics are fundamentally limited by rigid mechanics and wired interfaces that prevent conformal skin contact, producing poor signal quality and degraded long-term wearability. To address this critical shortcoming, this work consists of analytical, computational, empirical, and human subjects studies in soft materials and interfaces to enable a new class of wearable, wireless devices and sensors with mechanics finely tuned to transduce electrical, mechanical, and optical bio-signals from the human body, providing advanced diagnostic solutions to tackle some of the most pressing medical diagnostics challenges, both here in the United States and around the world.

 

]]> Laura Paige 1 1698755866 2023-10-31 12:37:46 1698755866 2023-10-31 12:37:46 0 0 event BioE PhD Defense Presentation- "A Skin-like Sternal Patch to Monitor Autonomic Tone During Cognitive Stress and Sympathetic Arousals in Disordered Sleep" -Nathan Zavanelli

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2023-11-16T10:00:00-05:00 2023-11-16T12:00:00-05:00 2023-11-16T12:00:00-05:00 2023-11-16 15:00:00 2023-11-16 17:00:00 2023-11-16 17:00:00 2023-11-16T10:00:00-05:00 2023-11-16T12:00:00-05:00 America/New_York America/New_York datetime 2023-11-16 10:00:00 2023-11-16 12:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Defense Presentation- Reza Bahranifard]]> 27917 Advisor:

Dr. Ross Ethier (BME, Georgia Institute of Technology)

 

Committee Members:

Dr. Stanislav Emelianov (BME, Georgia Institute of Technology)

Dr. Mark Prausnitz (ChBE, Georgia Institute of Technology)

Dr. Johnna Temenoff (BME, Georgia Institute of Technology)

Dr. Cheng Zhu (ME/BME, Georgia Institute of Technology)

 

Magnetic Steering to Save Sight: Trabecular Meshwork Cell Therapy as a Treatment for Primary Open Angle Glaucoma 

Glaucoma, which affects almost 80 million people worldwide, is the main cause of irreversible blindness. The most common type, primary open angle glaucoma (POAG), causes gradual loss of vision by damaging retinal ganglion cells. The major risk factor for POAG is high intraocular pressure (IOP).  Current clinical treatments for POAG aim to reduce IOP, but they often have low success rates. The trabecular meshwork (TM) is a key regulator of IOP and has been shown to undergo significant changes in POAG including a loss of cells. This motivates the regeneration or restoration of the TM as a potential treatment for POAG. While TM cell therapy has shown promise in reversal of POAG pathology, previously developed cell delivery techniques have resulted in poor cell delivery efficiency which elevates the risk of tumorigenicity and immunogenicity and undermines therapeutic potential. In addition, a lack of comprehensive characterization of the treatment effects in an appropriate POAG model is a roadblock to clinical translation. We here tackled these shortcomings by: 1) using an optimized magnetic delivery method to significantly improve the specificity and efficiency of delivery of cells to the mouse TM, in turn reducing the risk of unwanted side-effects, and 2) employing this optimized method to test the therapeutic capabilities of two types of cells in a mutant myocilin mouse model of ocular hypertension, characterizing the morphological and functional benefits of the treatment. The central hypothesis of this work is that an optimized magnetically-driven TM cell therapy can lead to long-term clinically significant levels of IOP reduction while minimizing the risks associated with unwanted off-target cell-delivery. This work resulted in the development of a novel magnetic TM cell therapy technique which outperformed those used previously. Employing this technique proved adipose-derived mesenchymal stem cells (hAMSC) and induced pluripotent stem cells differentiated towards a TM phenotype (iPSC-TM) to be effective in IOP lowering. Mesenchymal stem cells showed superior efficacy by stably lowering the IOP by 27% for 9 months, accompanied by increased cellularity in the conventional outflow pathway. These findings, bring magnetic TM cell therapy one step closer to clinical translation. 

]]> Laura Paige 1 1698755467 2023-10-31 12:31:07 1698755467 2023-10-31 12:31:07 0 0 event BioE PhD Defense Presentation - "Magnetic Steering to Save Sight: Trabecular Meshwork Cell Therapy as a Treatment for Primary Open Angle Glaucoma " - Reza Bahranifard

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2023-11-29T09:00:00-05:00 2023-11-29T11:00:00-05:00 2023-11-29T11:00:00-05:00 2023-11-29 14:00:00 2023-11-29 16:00:00 2023-11-29 16:00:00 2023-11-29T09:00:00-05:00 2023-11-29T11:00:00-05:00 America/New_York America/New_York datetime 2023-11-29 09:00:00 2023-11-29 11:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Defense Presentation- David Ryoo]]> 27917 Advisor:

Dr. James C. Gumbart (Physics, Georgia Institute of Technology)

 

Committee Members:

Dr. Julie Champion (ChBE, Georgia Institute of Technology)

Dr. Thomas DiChristina (Biology, Georgia Institute of Technology)

Dr. Harold Kim (Physics, Georgia Institute of Technology)

Dr. Todd Sulchek (ME, Georgia Institute of Technology)

 

Building through Thicket and Mesh: a Comprehensive Look at the Outer Membrane Environment of Gram-negative Bacteria

The antimicrobial resistance (AMR) of microorganisms is quickly becoming a growing concern for the human population. In particular, such resistance in Gram-negative bacteria has become a difficult case to crack, as the outer membrane (OM) of the Gram-negative bacteria provides a substantial physical and chemical barrier against small molecules. In order to elucidate how the OM environment contributes to the AMR of Gram-negative bacteria, we studied three aspects that this environment provides, the virulence factor export by autotransporters (ATs), the biogenesis of the outer membrane proteins (OMPs), and the cell envelope that OM is a part of. We first focused on the virulence factor export or passenger domain secretion of ATs, and how the ATs will secrete through the BamA barrel of the larger \textbeta-barrel assembly machinery (BAM) complex. Then, we examined the plausibility of the hybrid model of folding and insertion by BAM complex from the simulations of both constructed hybrid models and cryoEM-resolved structures. Finally, we interrogated the OM and cell wall structure connected by Braun's lipoprotein (Lpp) which more accurately depicts how the OM portion of the cell envelope would react against the turgor pressure. By examining these aspects of the Gram-negative bacteria, further developments to combat AMR of the Gram-negative bacteria can be made.

]]> Laura Paige 1 1697135585 2023-10-12 18:33:05 1697135585 2023-10-12 18:33:05 0 0 event BioE PhD Defense Presentation-  "Building through Thicket and Mesh: a Comprehensive Look at the Outer Membrane Environment of Gram-negative Bacteria" David Ryoo

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2023-10-26T10:00:00-04:00 2023-10-26T12:00:00-04:00 2023-10-26T12:00:00-04:00 2023-10-26 14:00:00 2023-10-26 16:00:00 2023-10-26 16:00:00 2023-10-26T10:00:00-04:00 2023-10-26T12:00:00-04:00 America/New_York America/New_York datetime 2023-10-26 10:00:00 2023-10-26 12:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Proposal Presentation- Kendreze Holland]]> 27917 Committee:

John Blazeck (Ph.D. Advisor)  (School of Chemical & Biomolecular Engineering)

Julie Champion (School of Chemical & Biomolecular Engineering)

Corey Wilson (School of Chemical & Biomolecular Engineering)

Felipe Quiroz (School of Biomedical Engineering, Emory)

William Ratcliff (School of Biological sciences)

  

 

A Novel Platform for Simultaneous Control of Multiple Genes at High Throughput

 

Complex cellular phenotypes and cars are similar in that one can observe their intended purpose (e.g., ability to survive for cells or mobility for cars) but struggle to understand the mechanisms that enable these features. While cars, because they are human-made, can undergo high throughput diagnostics to assess which parts combine to function to allow efficient mobility, methods with an analogous purpose do not exist for complex cellular phenotypes like their ability to survive. Particularly, numerous genes interact in parallel and non-parallel networks to give rise to these complex phenotypes, weakening the understanding gained by testing genes one at a time. In this vein, it is important to note that previous efforts with gene knockout and CRISPR activation/repression studies do not characterize the vast possibilities of achievable gene interactions per cell. Thus, the field of biology needs a high throughput investigative tool with enhanced characterization potential of these intricate gene networks that control complex phenotypes like survival in response to changing environments. To address this shortcoming, we have developed a novel method involving the high throughput creation of multi-single-guide RNA (sgRNA) cassettes. We have shown that it is feasible to assemble multiplex sgRNA cassettes by overlap extension polymerase chain reaction (OE-PCR), and that they can then allow for combinatorial gene expression control in the model organism, Saccharomyces cerevisiae. We will use our novel platform method to simultaneously activate and repress numerous genes to be able to enhance cell survival when exposed to extracellular stressors, such as hydrogen peroxide. Importantly, this technology will have applicability across eukaryotic organisms, providing “research mechanics” with a method that enables improved manipulation of cellular machinery—controlling the expression of multiple genes per cell in a high throughput manner, which is currently an impossible or at least very arduous task.

 

]]> Laura Paige 1 1695918902 2023-09-28 16:35:02 1695918902 2023-09-28 16:35:02 0 0 event BioE PhD Proposal Presentation- "A Novel Platform for Simultaneous Control of Multiple Genes at High Throughput" - Kendreze Holland

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2023-10-05T12:00:00-04:00 2023-10-05T14:00:00-04:00 2023-10-05T14:00:00-04:00 2023-10-05 16:00:00 2023-10-05 18:00:00 2023-10-05 18:00:00 2023-10-05T12:00:00-04:00 2023-10-05T14:00:00-04:00 America/New_York America/New_York datetime 2023-10-05 12:00:00 2023-10-05 02:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioEngineering Graduate Committee Meeting]]> 27917 The BioEngineering graduate committee will meet to review/approve program policies, program faculty applications and submitted student petitions.

]]> Laura Paige 1 1659711775 2022-08-05 15:02:55 1694536705 2023-09-12 16:38:25 0 0 event BioEngineering Graduate Committee Meeting

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2023-10-16T11:00:00-04:00 2023-10-16T12:00:00-04:00 2023-10-16T12:00:00-04:00 2023-10-16 15:00:00 2023-10-16 16:00:00 2023-10-16 16:00:00 2023-10-16T11:00:00-04:00 2023-10-16T12:00:00-04:00 America/New_York America/New_York datetime 2023-10-16 11:00:00 2023-10-16 12:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE Faculty Meeting]]> 27917 The BioEngineering Program faculty meet regularly during the semester to address program policies, events and future research and academic directions.

]]> Laura Paige 1 1610040275 2021-01-07 17:24:35 1692466610 2023-08-19 17:36:50 0 0 event BioE Faculty Meeting

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2023-12-12T11:00:00-05:00 2023-12-12T12:00:00-05:00 2023-12-12T12:00:00-05:00 2023-12-12 16:00:00 2023-12-12 17:00:00 2023-12-12 17:00:00 2023-12-12T11:00:00-05:00 2023-12-12T12:00:00-05:00 America/New_York America/New_York datetime 2023-12-12 11:00:00 2023-12-12 12:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE Faculty Meeting]]> 27917 The BioEngineering Program faculty meet regularly during the semester to address program policies, events and future research and academic directions.

]]> Laura Paige 1 1610040360 2021-01-07 17:26:00 1692466546 2023-08-19 17:35:46 0 0 event BioE Faculty Meeting

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2023-10-17T11:00:00-04:00 2023-10-17T12:00:00-04:00 2023-10-17T12:00:00-04:00 2023-10-17 15:00:00 2023-10-17 16:00:00 2023-10-17 16:00:00 2023-10-17T11:00:00-04:00 2023-10-17T12:00:00-04:00 America/New_York America/New_York datetime 2023-10-17 11:00:00 2023-10-17 12:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE Faculty Meeting]]> 27917 The BioEngineering Program faculty meet regularly during the semester to address program policies, events and future research and academic directions.

]]> Laura Paige 1 1610040444 2021-01-07 17:27:24 1692466297 2023-08-19 17:31:37 0 0 event BioE Faculty Meeting

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2023-08-31T11:00:00-04:00 2023-08-31T12:00:00-04:00 2023-08-31T12:00:00-04:00 2023-08-31 15:00:00 2023-08-31 16:00:00 2023-08-31 16:00:00 2023-08-31T11:00:00-04:00 2023-08-31T12:00:00-04:00 America/New_York America/New_York datetime 2023-08-31 11:00:00 2023-08-31 12:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE MS Thesis Presentation- Esther Kim]]> 27917 Committee:

Bilal Haider, Ph.D. (Advisor) (Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology)

Christopher Rozell, Ph.D. (School of Electrical Engineering, Georgia Institute of Technology)

Stanislav Emilanov, Ph.D.  (School of Electrical Engineering, Georgia Institute of Technology)

  

 

 

CORTEX-WIDE CALCIUM IMAGING OF VISUALLY EVOKED NEURAL POPULATION ACTIVITY IN MOUSE VISUAL CORTEX

 

The traditional method of electrophysiology provides cellular-level, millisecond timescale measurements of neural activity, but it has limitations in probing neural activity across large spatial scales. Widefield imaging (WFI) of genetically engineered calcium-sensitive fluorescence proteins in neurons enables measurements of neural population activity across large areas (~ 5 x 5 mm) with temporal resolution of tens to hundreds of milliseconds. In this thesis, we adapted an experimental and analytical framework for WFI investigation of visually evoked neural activity across the mouse visual cortex. We first validated identification of the primary visual cortex (V1) and higher visual areas (HVAs) through retinotopic mapping experiments. We then measured stimulus-triggered calcium signals in mice performing a visual detection task. The activity profiles were analyzed as a function of task performance and were also compared to profiles measured in mice passively viewing the same visual stimuli with no task. We performed region of interest (ROI) analysis based on the retinotopically registered images across multiple visual areas.  The calcium signal amplitude was positively correlated with stimulus contrast, and signal amplitudes were enhanced during visual detection compared to passive viewing. Further work such as optimizing system functionality and applying a more efficient decomposition method on the WFI data could reduce variability across different imaging data sets and provide more accurate understanding of network dynamics across visual areas and other cortical regions.

]]> Laura Paige 1 1692463648 2023-08-19 16:47:28 1692463648 2023-08-19 16:47:28 0 0 event BioE MS Thesis Presentation- "CORTEX-WIDE CALCIUM IMAGING OF VISUALLY EVOKED NEURAL POPULATION ACTIVITY IN MOUSE VISUAL CORTEX" -Esther Kim

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2023-08-22T14:00:00-04:00 2023-08-22T16:00:00-04:00 2023-08-22T16:00:00-04:00 2023-08-22 18:00:00 2023-08-22 20:00:00 2023-08-22 20:00:00 2023-08-22T14:00:00-04:00 2023-08-22T16:00:00-04:00 America/New_York America/New_York datetime 2023-08-22 02:00:00 2023-08-22 04:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Defense Presentation- Lindsey Trejo]]> 27917 Zoom Link: https://gatech.zoom.us/j/5374686038

 

Advisor: 

Greg Sawicki, Ph.D. (Georgia Institute of Technology) 

Thesis Committee: 

Young-Hui Chang, Ph.D. (Georgia Institute of Technology) 

Young Jang, Ph.D. (Georgia Institute of Technology) 

Sabrina Lee, Ph.D. (Simon Fraser University) 

Rich Mahoney, Ph.D. (Intuitive) 

 

Interaction of ankle exoskeleton assistance with age-related changes in physiology to reduce metabolic cost of walking

Difficulties with mobility were the most commonly reported disability for those age 65 and over. It is well known that older adults are slower and less economical during walking compared to young. This is thought to be brought on by reduced ankle push off power and a redistribution of positive power generation to more proximal joints (e.g., hip). Ankle exoskeletons have been shown to increase ankle push off, increase self-selected speed, and reduce metabolic cost in young adults for a near immediate improvement in walking performance. There is a critical gap in understanding whether beneficial exoskeleton assistance strategies for younger adults will also benefit older adults and if so, what the underlying mechanism is that enables exoskeletons to reduce metabolic cost across age.

 

Older adults have more compliant tendons than young, or a less stiff spring, operate with shorter less optimal muscle lengths, and exhibit reduced push-off power leading to a loss of the ‘spring in their step’. This necessitates higher muscle activations and reliance on muscles at less efficient joints like the hips, increasing metabolic cost during walking. Passive ankle exoskeletons have been shown in younger adults to lower the demand at the ankle, optimize complicated muscle-tendon dynamics during stance, and reduce metabolic cost. Muscle level changes in young adults in response to ankle exoskeletons to reduce metabolic cost led to wondering how ankle exoskeletons interact with age-related changes in physiology to reduce metabolic cost. The near-term objective of my work was to evaluate the calf muscles and tendon’s role in modifying metabolic cost during walking with passive, and active ankle exoskeletons across age. My central hypothesis was ankle exoskeletons can offset age-related changes in physiology to reduce metabolic cost to that of young walking economy.

 

I used electromyography to measure muscle activity, B-mode ultrasound to track muscle level changes, and a portable indirect calorimetry system to measure metabolic cost in young and older adults with passive and active exoskeleton conditions. These aims yielded a greater understanding of how people interact with ankle exoskeletons to modify metabolic cost. These outcomes can improve the design and control of ankle exoskeletons to improve the cost of walking across age, leading to greater mobility and increased quality of life. The aims also clarified whether passive or active control is best for young or older adults. Passive devices are lighter weight, require less maintenance, and are easier to conceal but they are less tunable and have shown lower reductions in metabolic cost. Active devices can be optimized for each person and provide more assistance at any timepoint in the gait cycle. However, motors and batteries make a lightweight device difficult to create and complicates usage with maintenance, battery life, bulkiness, and noise. Completion of the aims, pave the way for studies in more functional measures such as increasing self-selected walking speed, improving balance, and reducing fatigue that may translate more directly to improved quality of life.

]]> Laura Paige 1 1691168215 2023-08-04 16:56:55 1691168215 2023-08-04 16:56:55 0 0 event BioE PhD Defense Presentation- "Interaction of ankle exoskeleton assistance with age-related changes in physiology to reduce metabolic cost of walking" - Lindsey Trejo

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2023-08-14T15:00:00-04:00 2023-08-14T17:00:00-04:00 2023-08-14T17:00:00-04:00 2023-08-14 19:00:00 2023-08-14 21:00:00 2023-08-14 21:00:00 2023-08-14T15:00:00-04:00 2023-08-14T17:00:00-04:00 America/New_York America/New_York datetime 2023-08-14 03:00:00 2023-08-14 05:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE MS Thesis Presentation- Rodney Ridley]]> 27917 Committee:

Kostas Konstantinidis, Ph.D. (Advisor) (School of Civil and Environmental Engineering, Georgia Institute of Technology)

Blair Brettmann, Ph.D. (School of Chemical and Biomolecular Engineering, Georgia Institute of Technology)

Thomas DiChristina, Ph.D.  (School of Biological Sciences, Georgia Institute of Technology)

 

 

Multi-omic Investigation of Plastic-Associated Microbes: Bioinformatic Insights into Plastic Biodegradation and Novel Degrading Genes across Environments

 

Synthetic plastics and their resulting waste are ubiquitous across the planet, from the Arctic to the tropics. Despite increasing efforts to understand the fate and transport of these plastics, their impact on the environment and public health is still not well understood. To better comprehend the microbial ecology associated with plastic waste and its potential for bioremediation, we conducted a large-scale analysis of all publicly available meta-omic studies investigating plastics in the environment. Importantly, we observed low prevalence of previously reported plastic degrading populations throughout most environments, except for substantial enrichment in riverine systems. This indicates rivers may be the one of the most promising environments for sources of plastic bioremediation. Ocean samples associated with degrading plastics showed clear differentiation between non-degrading polymers, showing enrichment for novel putative biodegrading taxa. In regards to plastisphere pathogenicity, we observe no association between virulence factors and plastics in any environment. Additionally, we report a co-occurrence network analysis of 10+ million proteins associated with the plastisphere. This analysis shows a localized sub-region enriched with known and putative plastizymes. These novel putative plastizymes may be useful for deeper investigations of nature’s ability to biodegrade man-made plastics. Finally, the combined data from this meta-analysis was used to construct a publicly available database. These data should allow for integrated exploration of the microbial plastisphere and aid the community in continued research efforts.

]]> Laura Paige 1 1690557368 2023-07-28 15:16:08 1690557368 2023-07-28 15:16:08 0 0 event BioE MS Thesis Presentation- "Multi-omic Investigation of Plastic-Associated Microbes: Bioinformatic Insights into Plastic Biodegradation and Novel Degrading Genes across Environments" - Rodney Ridley

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2023-08-10T12:00:00-04:00 2023-08-10T14:00:00-04:00 2023-08-10T14:00:00-04:00 2023-08-10 16:00:00 2023-08-10 18:00:00 2023-08-10 18:00:00 2023-08-10T12:00:00-04:00 2023-08-10T14:00:00-04:00 America/New_York America/New_York datetime 2023-08-10 12:00:00 2023-08-10 02:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Defense Presentation- Lindsey Trejo]]> 27917 Zoom Link: https://gatech.zoom.us/j/5374686038

 

Advisor: 

Greg Sawicki, Ph.D. (Georgia Institute of Technology) 

Thesis Committee: 

Young-Hui Chang, Ph.D. (Georgia Institute of Technology) 

Young Jang, Ph.D. (Georgia Institute of Technology) 

Sabrina Lee, Ph.D. (Simon Fraser University) 

Rich Mahoney, Ph.D. (Intuitive) 

 

Interaction of ankle exoskeleton assistance with age-related changes in physiology to reduce metabolic cost of walking

Difficulties with mobility were the most commonly reported disability for those age 65 and over. It is well known that older adults are slower and less economical during walking compared to young. This is thought to be brought on by reduced ankle push off power and a redistribution of positive power generation to more proximal joints (e.g., hip). Ankle exoskeletons have been shown to increase ankle push off, increase self-selected speed, and reduce metabolic cost in young adults for a near immediate improvement in walking performance. There is a critical gap in understanding whether beneficial exoskeleton assistance strategies for younger adults will also benefit older adults and if so, what the underlying mechanism is that enables exoskeletons to reduce metabolic cost across age.

 

Older adults have more compliant tendons than young, or a less stiff spring, operate with shorter less optimal muscle lengths, and exhibit reduced push-off power leading to a loss of the ‘spring in their step’. This necessitates higher muscle activations and reliance on muscles at less efficient joints like the hips, increasing metabolic cost during walking. Passive ankle exoskeletons have been shown in younger adults to lower the demand at the ankle, optimize complicated muscle-tendon dynamics during stance, and reduce metabolic cost. Muscle level changes in young adults in response to ankle exoskeletons to reduce metabolic cost led to wondering how ankle exoskeletons interact with age-related changes in physiology to reduce metabolic cost. The near-term objective of my work was to evaluate the calf muscles and tendon’s role in modifying metabolic cost during walking with passive, and active ankle exoskeletons across age. My central hypothesis was ankle exoskeletons can offset age-related changes in physiology to reduce metabolic cost to that of young walking economy.

 

I used electromyography to measure muscle activity, B-mode ultrasound to track muscle level changes, and a portable indirect calorimetry system to measure metabolic cost in young and older adults with passive and active exoskeleton conditions. These aims yielded a greater understanding of how people interact with ankle exoskeletons to modify metabolic cost. These outcomes can improve the design and control of ankle exoskeletons to improve the cost of walking across age, leading to greater mobility and increased quality of life. The aims also clarified whether passive or active control is best for young or older adults. Passive devices are lighter weight, require less maintenance, and are easier to conceal but they are less tunable and have shown lower reductions in metabolic cost. Active devices can be optimized for each person and provide more assistance at any timepoint in the gait cycle. However, motors and batteries make a lightweight device difficult to create and complicates usage with maintenance, battery life, bulkiness, and noise. Completion of the aims, pave the way for studies in more functional measures such as increasing self-selected walking speed, improving balance, and reducing fatigue that may translate more directly to improved quality of life.

]]> Laura Paige 1 1690488574 2023-07-27 20:09:34 1690488574 2023-07-27 20:09:34 0 0 event BioE PhD Defense Presentation "Interaction of ankle exoskeleton assistance with age-related changes in physiology to reduce metabolic cost of walking" - Lindsey Trejo

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<![CDATA[BioE PhD Proposal Presentation- Likhit Nayak]]> 27917 Advisor:

Rudy Gleason, Ph.D.                   Mechanical Engineering, Georgia Tech

 

Committee:

Brandon Dixon, Ph.D.                  Mechanical Engineering, Georgia Tech

Wilbur Lam, Ph.D.                        Biomedical Engineering, Georgia Tech

May Wang, Ph.D.                         Biomedical Engineering, Georgia Tech

Mike Weiler, Ph.D.                      LymphaTech, Inc.

 

 

Real-time risk-assessment of Cephalopelvic Disproportion (CPD) in pregnant women using longitudinal shape modeling of 3D scans.

Cephalopelvic disproportion (CPD) is a mismatch in the size of the maternal pelvis and the fetus, which often leads to obstructed labor. Most cases of CPD require C-section for successful delivery and in low resource settings like Ethiopia, there is a lack of adequate facilities with the infrastructure or expertise to perform a C-section. Currently, obstructed labor is known to account for 11 – 22% of maternal deaths in Ethiopia. Early assessment of the risk of CPD would enable women in these settings to access the proper healthcare services and improve the overall maternal health. This thesis aims to develop a point-of-care tool that would use longitudinal shape modeling to analyze, in real-time, 3D scans of pregnant women and assess the risk of CPD-related obstructed labor at the earliest possible stages of gestation. The longitudinal shape model would be trained on 3D scans of pregnant women across different periods of gestation and would be optimized to run on devices with low computational power. The developed tool is envisioned to be used by nurses and midwife personnel as part of routine antenatal care in low-resource settings.

]]> Laura Paige 1 1690488396 2023-07-27 20:06:36 1690488396 2023-07-27 20:06:36 0 0 event BioE PhD Proposal Presentation- "Real-time risk-assessment of Cephalopelvic Disproportion (CPD) in pregnant women using longitudinal shape modeling of 3D scans." - Likhit Nayak

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<![CDATA[BioE PhD Proposal Presentation- Erin Shappell]]> 27917 Advisor:

Hang Lu, Ph.D.                    Chemical and Biomolecular Engineering, Georgia Tech

 

Committee:

Eva Dyer, Ph.D.                        Biomedical Engineering, Georgia Tech

Gordon Berman, Ph.D.            Biology, Emory University

Simon Sponberg, Ph.D.            Physics and Biological Sciences, Georgia Tech

Patrick McGrath, Ph.D.         Biology, Georgia Tech

 

 

To eat, or not to eat: A deep learning pipeline for quantifying the contribution of monoamines to feeding-related decisions in C. elegans

Hunger is the universal drive to eat. However, the decision to eat or not eat is dependent on more than just hunger signaling; organisms can sometimes experience hunger but choose not to eat. The decision to not eat despite feeling hungry can become chronic and pathological, leading to the development of an eating disorder. Despite extensive knowledge of the signals that control hunger, we do not fully understand the origins and mechanisms of pathological eating-related decision making in humans. The challenges associated with studying this problem in humans may be greatly reduced, without sacrificing biological relevance, through the study of a simpler organism such as C. elegans. C. elegans is a soil-dwelling microscopic nematode with many evolutionary connections to humans whose eating behavior has been widely studied. No group has successfully identified the source(s) of eating-related decision making in C. elegans, but the tools necessary to do so exist. This thesis will refine and combine existing technologies, including deep learning methods and a scalable microscopy system, to measure the effects of two evolutionarily-conserved monoamines on the timescale of eating- related decisions in C. elegans. To do this, eating behavior will first be measured using three methods: a newly proposed pipeline to track eating rate, Faster R-CNN to track worm motion, and DeepLabCut to track worm posture. These eating features will then be compiled into a map of eating “states” (i.e., distinct types of eating) using an existing pipeline called MotionMapper. Then, eating state maps will be calculated across worms that lack the monoamines of interest; these will be compared to identify how each monoamine controls the length, frequency, and timing of the transitions between different types of eating. We anticipate that the findings from this work will reveal a basic model of how monoamines control eating-related decisions.

]]> Laura Paige 1 1687888183 2023-06-27 17:49:43 1687888183 2023-06-27 17:49:43 0 0 event BioE PhD Proposal Presentation- "To eat, or not to eat: A deep learning pipeline for quantifying the contribution of monoamines to feeding-related decisions in C. elegans" - Erin Shappell

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<![CDATA[BioE PhD Defense Presentation- Jacob Davis]]> 27917 Committee:
Eberhard Voit, Ph.D. (Advisor) (Department of Biomedical Engineering, Georgia Institute of Technology and Emory University)
Sam Brown, Ph.D. (Advisor)  (School of Biological Sciences, Georgia Institute of Technology)
Melissa Kemp, Ph.D  (Department of Biomedical Engineering, Georgia Institute of Technology and Emory University)
Arlene Stecenko, M.D. (Department of Pediatrics, Emory University School of Medicine)
Mark Styczynski, Ph.D (School of Chemical and Biomolecular Engineering, Georgia Institute of Technology)
Denis Tsygankov, Ph.D (Department of Biomedical Engineering, Georgia Institute of Technology)

 

EXPERIMENTAL AND COMPUTATIONAL ANALYSIS OF PATHOGEN EMERGENCE AND ANTIBIOTIC RESISTANCE IN A CYSTIC FIBROSIS AIRWAY INFECTION MODEL

 

    The human body harbors at least twice as many bacteria as it does human cells. Most of these bacteria are harmless, but the emergence of pathogens is common in many human body systems. Treatment of these infections is often done with antibiotics, which can have non-target effects and remove protective flora from the body. This project was designed to create a model system of airway bacterial communities that is amenable to the development of effective experimental and computational investigations that shed light on pathogen emergence and antibiotic resistance. For the experimental analysis, I transformed three bacterial species found in human airways with the goal of making them easily quantifiable with available microscopic and spectrophotometric techniques. The bacteria were grown individually and in combinations of species and their dynamics were studied, as well as the effects of pH on the system. Community resistance to a beta-lactam was studied by tracking the hydrolyzation of the antibiotic by non-targeted species, showing that non-focal species are important to consider when choosing an antibiotic treatment. To quantify interactions among the different species, mathematical models within the Lotka-Volterra framework were developed and parameterized. The existing framework was then expanded to incorporate antibiotic and metabolic data in the community model. Although the community size of the model system is small - to allow for comprehensive data generation - this experimental and mathematical system constitutes a prototype for investigating larger models that can be used to predict how pathogens survive in different communities and under altered environmental conditions and antibiotic treatments.

]]> Laura Paige 1 1686836230 2023-06-15 13:37:10 1686856304 2023-06-15 19:11:44 0 0 event BioE PhD Defense Presentation-  "EXPERIMENTAL AND COMPUTATIONAL ANALYSIS OF PATHOGEN EMERGENCE AND ANTIBIOTIC RESISTANCE IN A CYSTIC FIBROSIS AIRWAY INFECTION MODEL" - Jacob Davis

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<![CDATA[BioE PhD Proposal Presentation- Felicia Davenport]]> 27917 Time and Date: 2:00 PM, Thursday, May 18th, 2023

Location: J. Erskine Love Building – Room 210

Zoom: https://gatech.zoom.us/j/98109368835?pwd=Tmtybmg2WDRrN2JTYU9TREVjQUM0dz09

Meeting ID: 981 0936 8835 | Passcode: 460155

 

Advisor:

Gregory Sawicki, Ph.D. (Georgia Institute of Technology)

Thesis Committee:

Aaron Young Ph.D. (Georgia Institute of Technology)

Omer Inan, Ph.D. (Georgia Institute of Technology)

Karl Zelik, Ph.D. (Vanderbilt University)

Ajit Chaudhari, Ph.D. (Ohio State University)

 

Joint Loading in Industrial Lifts:  Informing Mitigation Strategies through Joint-Level Biomechanics

Work-related injuries due to overexertion remain a leading cause of health problems in manual occupations. Manual labor personnel often perform variations of repetitive lifting and twisting under loads throughout their workday. Prolonged exposure to mechanical loading can lead to strain in soft tissues and degradation in bones that can lead to prominent chronic ailments such as low back pain and osteoarthritis which continue to plague the workforce, with about 50% of reported injuries stemming from the back or knee. Chronic bone injuries are tricky to identify in the early stages as it’s difficult to measure in vivo and a considerable amount of deterioration is needed to register the pain. Joint contact forces capture the internal force felt by the bone and can be estimated through computational neuromusculoskeletal modeling methods. Thus, providing insight on internal joint loading. Therefore, there is a critical gap in understanding and mitigating injuries from chronic joint loading in the back and knee.

Despite initiatives implemented in the workplace to combat chronic overexertion injuries such as methodology training and commercial braces, the problems seem to prevail without a known resolution. In the first aim of the proposed project, I seek to develop a framework which characterizes joint contact forces across work-specific lifting tasks in the back and the knee and identifies tasks in need of assistance. Modern technology has shown promising results to addressing deficits in human capabilities. Exoskeletons have shown reductions in energy expenditure, muscle activity, and joint loading. Since muscle forces are known to be the dominate factor in contributing to joint contact forces, exoskeletons may be a suitable intervention to harmful joint loading. The second aim of my proposed work intends to investigate the effects of exoskeletons on joint contact forces. I hypothesize that prescribing a back and knee exoskeleton can reduce joint contact forces by lowering muscle activity in work-specific tasks. Advances in machine learning have also proven effective at estimating and predicting biological metrics such as kinematics and kinetics from wearable sensors. The objective of the third aim is to create a system to estimate joint contact forces using machine learning technologies and determine the minimal amount of input data required for reliable performance.

Electromyography (EMG) will be used to measure muscle activity and computational software (OpenSim and the Calibrated EMG-Informed Neuromusculoskeletal Modeling Toolbox (CEINMS)) will calculate joint kinematics, kinetics, and contact forces with (1) no exoskeleton, (2) an active knee exoskeleton, and (3) a passive back exoskeleton. Later, a wearable sensor-driven machine learning algorithm will be used to estimate joint contact forces. Successful completion of the aims will prove beneficial to ergonomists, clinicians, and applied engineers alike by informing rehabilitation strategies, exoskeleton design and controllers, and real-time biofeedback systems. 

 

 

]]> Laura Paige 1 1684358498 2023-05-17 21:21:38 1684358498 2023-05-17 21:21:38 0 0 event BioE PhD Proposal Presentation- "Joint Loading in Industrial Lifts:  Informing Mitigation Strategies through Joint-Level Biomechanics" - Felicia Davenport

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<![CDATA[BioE PhD Defense Presentation- Elio Challita]]> 27917 Advisor: Saad Bhamla, Ph.D. (Georgia Institute of Technology)

Committee:

David Hu, Ph.D. (Georgia Institute of Technology)

Sunghwan ‘Sunny’ Jung, Ph.D. (Cornell University)

Sheila Patek, Ph.D. (Duke University)

Simon Sponberg, Ph.D. (Georgia Institute of Technology)

 

Fast and Furious: Principles of droplets, jets, and damping in ultrafast Invertebrates

 

This thesis presentation delves into the world of tiny ultrafast organisms, specifically sharpshooters, springtails, and slingshot spiders, to explore the role of fluid dynamics in their rapid biological movements.

 

In the first part, we investigate the fluidic, energetic, and biomechanical principles that enable sharpshooter insects (Hemiptera: Cicadellidae) to thrive on a nutrient-sparse xylem sap diet. We examine their remarkable superpropulsion strategy during droplet ejection through the temporal coordination between the stylus and the droplet. Employing experimental, mathematical, and computational approaches, we explore the physical limits of this unique droplet propulsion strategy and demonstrate why it is energetically favorable for these insects to fling their droplet excreta instead of using alternative mechanisms such as 'jetting' and 'dripping'. Using dimensionless analysis, we show how biological organisms living in a world governed by surface tension develop novel strategies to overcome capillary adhesion during fluidic ejection.

 

In the second part of the presentation, we introduce a mathematical framework for the arrest and damping of ultra-fast movements in biological organisms. We contextualize and validate this framework through field and lab experiments on two organisms: the rapid launch of slingshot spiders (Araneae: Theridiosomatidae) and the controlled landing of semi-aquatic springtails (Arthropoda: Collembola) at the water-air interface. For slingshot spiders, we demonstrate how these organisms use their tension line and viscous drag to halt their ultra-fast movements. For springtails, we investigate the adhesive landing mechanisms employed by these creatures on water surfaces, revealing how collophore adhesion assists in controlling their upward movement after reaching maximum depth.

 

By analyzing the movement of these extreme invertebrates through physics-based arguments, we unveil how these finely tuned ultrafast organisms harness their structure-fluid interactions to survive and fulfill their biological functions, including excretion, predation, and predator avoidance.

]]> Laura Paige 1 1682600359 2023-04-27 12:59:19 1682600359 2023-04-27 12:59:19 0 0 event BioE PhD Defense Presentation- "Fast and Furious: Principles of droplets, jets, and damping in ultrafast Invertebrates"  -  Elio Challita

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<![CDATA[BioE PhD Defense Presentation-Alyssa Pybus]]> 27917 Advisor:

Levi Wood, PhD (Georgia Institute of Technology)

 

Committee:

Erin Buckley, PhD (Georgia Institute of Technology)

Michelle LaPlaca, PhD (Georgia Institute of Technology)

Manu Platt, PhD (Georgia Institute of Technology, NIH NIBIB)

Srikant Rangaraju, MD MS (Emory University) 

 

Profiling the Neuroimmune Cascade after Repetitive Mild Traumatic Brain Injury

 

Mild traumatic brain injury (mTBI) is responsible for about 2 million emergency department visits and an estimated cost burden of $17 billion in the United States every year. Moreover, repeated mTBI (rmTBI) can result in cumulative effects and worse clinical outcomes than a single injury. Despite its prevalence and cost, current treatment for mTBI is severely lacking and targets symptoms rather than drivers of adverse clinical outcomes. Research into new therapeutic strategies for the treatment of mTBI patients is constrained by our limited understanding of the biological mechanisms behind how brain injury impacts outcomes, such as cognitive deficit and neurodegenerative pathology similar to that seen in Alzheimer’s disease (AD). Recent studies unveil new evidence that neuroimmune signaling may be a key driver of long-term outcome after single or repeated mTBI, but there remains an urgent need to identify the specific cellular and molecular pathways involved to assess their potential for targeting in new therapeutic intervention strategies. The work of this dissertation seeks to comprehensively define the neuroimmune response to single and repeated mTBI alongside cognitive and pathological outcome measures to improve our understanding of brain injury and propose potential targets for therapeutic intervention. 

The present work uses in vivo murine models of rmTBI to determine the acute effects of injury on neuroimmune signaling in correlation to biomarkers of cognitive and pathological outcome. Our findings in wild type mice suggest that elevated neuroimmune signaling is strongly linked to cognitive outcome (Aim 1). Next, we used transgenic mice capable of displaying human-like pathology to relate neuroimmune signaling to pathological outcomes (Aim 2). We identified specific cytokines elevated after injury in correlation to markers of AD-like pathology, suggesting involvement with brain injury-induced pathogenesis and potential for use as diagnostic or prognostic clinical biomarkers. Interestingly, we found that cytokines correlated to outcome in both aims were primarily localized to neurons, suggesting a previously unappreciated role of immune regulation by neurons. Lastly, transcriptional profiling revealed rapid neuronal dysfunction within 24 hours after injury followed by changes in astrocyte- and microglia-related gene expression within days.  Collectively, our data suggest rapid changes in specific neuronal pathways involved in immune signaling after injury, followed by changes in other cell types. These findings support the need for future work to assess the efficacy of therapeutic targeting of neuroimmune signaling to improve outcomes after single and repeated mTBI.

]]> Laura Paige 1 1681736235 2023-04-17 12:57:15 1681736235 2023-04-17 12:57:15 0 0 event BioE PhD Defense Presentation- "Profiling the Neuroimmune Cascade after Repetitive Mild Traumatic Brain Injury" - Alyssa Pybus

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<![CDATA[BioE MS Thesis Defense- Sujay Kestur]]> 27917 Committee:
Aaron Young, Ph.D. (Advisor) (School of Mechanical Engineering, Georgia Institute of Technology)
Kinsey Herrin, M.S., CPO (School of Mechanical Engineering, Georgia Institute of Technology)
Young-Hui Chang, Ph.D.  (School of Biological Sciences, Georgia Institute of Technology)

 
 

Comparing the Biomechanics of Powered and Passive Microprocessor Knees during Community Ambulation Tasks

              Many individuals undergo lower limb amputations as a result of various conditions such as diabetes, vascular diseases, cancer and trauma. The use of a lower limb prostheses is one of the most common solutions to return the ability to complete locomotion tasks of daily living to this population. As the number of amputees is predicted to grow, advances in prosthetic technology have been made to improve patient mobility and quality of life. One of the most significant of these developments has been the introduction of the Microprocessor Prosthetic Knee (MPK). This type of prosthesis is designed to better mimic the natural movement of the knee joint and improve stability, mobility and safety during locomotion. 

              However, there is still a debate over which type of MPK results in better performance: a passive or a powered device. In addition, it remains unclear to what degree one type of MPK has an advantage over the other and specifically during which locomotion modes is this advantage present. Few studies have been done comparing the use of commercial powered and passive MPKs and how these devices affect different aspects of the user's biomechanics. The aim of this study is to address this research gap.  

              In this thesis, an experiment was conducted in which individuals with transfemoral amputation performed various community ambulation tasks while wearing one of three commercial MPKs: the Össur Power Knee, the Össur Rheo Knee and the Ottobock C-Leg 4. The Power Knee is a powered device while the Rheo and C-Leg are passive devices. Several biomechanics variables were analyzed and the evaluation of the prosthesis' performance was determined based on the amount of biological joint energy used. Additionally, an evaluation of the modeling of powered devices was performed in order to validate the inverse dynamics being obtained from them. This thesis covers the experimental procedures performed, an analysis of the results and the further efforts made to improve the modeling of powered prosthetic devices.

]]> Laura Paige 1 1681494852 2023-04-14 17:54:12 1681494852 2023-04-14 17:54:12 0 0 event BioE MS Thesis Defense- "Comparing the Biomechanics of Powered and Passive Microprocessor Knees during Community Ambulation Tasks" - Sujay Kestur

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<![CDATA[BioE PhD Defense Presentation- Mighten Yip]]> 27917 Advisor:

Craig Forest, PhD (Georgia Institute of Technology)

 

Committee:

Ming-fai Fong, PhD (Georgia Institute of Technology)

Brandon Dixon, PhD (Georgia Institute of Technology)

Christopher Valenta, PhD (Georgia Tech Research Institute)

Matt Rowan, PhD (Emory University)

Stephen Traynelis, PhD (Emory University)

 

Towards automation of multimodal cellular electrophysiology

Understanding how neurons of the brain communicate, connect, and respond to stimuli is a fundamental goal of neuroscience. Whole-cell patch clamp recording in vitro represents the gold standard method for measuring electrophysiology of single neurons because of its high spatiotemporal resolution. However, the manual and time-consuming nature of patch clamping experiments has limited the throughput and number of cells that can be sampled per day. To overcome these limitations, this dissertation aimed to (1) integrate automated patch clamp with discovery experiments for cellular indicators and effectors, (2) develop a machine learning algorithm for real-time neuron detection of neurons in brain slices for in vitro patch clamping, and (3) create a coordinated, multi-pipette patch clamp algorithm for enabling high throughput synaptic connectivity studies. Towards these aims, this thesis demonstrated the first robotic system to perform ligand-gated ionotropic receptor protocols autonomously leading up to a 10-fold reduction in research effort over the duration of the experiment. In addition, a fully automated patch clamp robot was deployed to discover a brighter and more sensitive chemigenetic voltage indicator, Voltron2, over its predecessor exhibiting 3-fold higher sensitivity in response to sub-threshold membrane potential changes. Towards the second aim, a novel, deep learning-based method was developed to accomplish automated, real-time neuron detection in brain slice with high accuracy, achieving an F1 score of 80%. To facilitate efficient probing of local synaptic connections between neurons, the first ever forward-thinking multipatching robot demonstrated automatic, sequential recordings in a brain slice using a coordinated route plan. With these technologies combined, this thesis enabled the first robot that can automatically search for connected neurons in brain tissue and also outperforms manual patch clamping-based screening assays to significantly advance the field of neuroscience and reveal new insights into brain function.

]]> Laura Paige 1 1681418675 2023-04-13 20:44:35 1681418675 2023-04-13 20:44:35 0 0 event BioE PhD Defense Presentation- "Towards automation of multimodal cellular electrophysiology" - Mighten Yip

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<![CDATA[BioE PhD Proposal Presentation- M. Reza Bahranifard]]> 27917 Advisor:

C. Ross Ethier, Ph.D. (BME, Georgia Tech)

Committee:

Stanislav Emelianov, Ph.D. (BME, Georgia Tech)

Cheng Zhu, Ph.D. (ME, Georgia Tech)

Mark Prausnitz, Ph.D. (ChE, Georgia Tech)

Johnna Temenoff, Ph.D. (BME, Georgia Tech)

 

MAGNETIC STEERING TO SAVE SIGHT: TRABECULAR MESHWORK CELL THERAPY AS A TREATMENT FOR PRIMARY OPEN ANGLE GLAUCOMA

Glaucoma, which affects almost 80 million people worldwide, is the main cause of irreversible blindness. The most common type, primary open angle glaucoma (POAG), causes a gradual loss of vision by damaging retinal ganglion cells. The major risk factor for POAG is high intraocular pressure (IOP).

Current clinical treatments for POAG aim to reduce IOP, but they often have low success rates. The trabecular meshwork (TM) is a key regulator of IOP and has been shown to undergo significant changes in POAG including a loss of cells. This motivates the regeneration or restoration of the TM as a potential treatment for POAG. While TM cell therapy has shown promise in reversal of POAG pathology, previously-developed cell delivery techniques have resulted in poor cell delivery efficiency which elevates the risk of tumorigenicity and immunogenicity and undermines therapeutic potential. In addition, a lack of comprehensive characterization of the treatment effects in an appropriate POAG model is a roadblock to clinical translation.

We here tackle these shortcomings by: 1) using an optimized magnetic cell delivery method to significantly improve the specificity and efficiency of delivery of stem cells to the TM, in turn reducing the risk of unwanted side-effects, and 2) employing this optimized method to test the therapeutic capabilities of two types of cells in the current best mouse model of POAG, characterizing the morphological and functional benefits of the treatment. The central hypothesis of this work is that an optimized magnetically-driven TM cell therapy can restore IOP homeostasis while minimizing unwanted off-target cell-delivery effects.

 

]]> Laura Paige 1 1680705393 2023-04-05 14:36:33 1680705393 2023-04-05 14:36:33 0 0 event BioE PhD Proposal Presentation- "MAGNETIC STEERING TO SAVE SIGHT: TRABECULAR MESHWORK CELL THERAPY AS A TREATMENT FOR PRIMARY OPEN ANGLE GLAUCOMA"- M. Reza Bahranifard

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<![CDATA[BioE PhD Defense Presentation- D. Andre Norfleet]]> 27917 Advisor:

Melissa Kemp, PhD (Biomedical Engineering)

 

Committee:

Craig Forest, PhD (Mechanical Engineering)

Ravi Kane, PhD (Chemical and Biomolecular Engineering)

Sung Jin Park, PhD (Biomedical Engineering)

Manu Platt, PhD (Biomedical Engineering)

Eberhard Voit, PhD (Biomedical Engineering)

 

Metabolic and Bioelectric Crosstalk in Directed Differentiation and Spatial Patterning of iPSC-derived Cardiomyocytes

The goal of multi-cellular engineered living systems is the design and manufacturing of multi-cellular systems with novel form or function using engineering design principles. Induced pluripotent stem cells represent an excellent tool to enable actualization of these design goals because of their intrinsic pluripotent capacity and previous recapitulation of various embryogenesis and organogenesis processes. The objective of this research was to investigate through computational modeling how molecular components of bioelectric and metabolic systems alter multicellular bioelectric patterning and cell metabolic flux dynamics, and to this extend system understanding to guide emergent morphogenic outcomes via external modulation of the culturing environment. The central hypothesis of this work was that specific media compositions can alter molecular components of bioelectric and metabolic multicellular systems in a predictable manner, leading to desired morphologies, cell phenotypes, and novel functionalities. In the first study, In multi-scale bioelectric computational model describing human iPSC tissue-scale membrane voltage potentials (Vmem) was developed to understand unexplored patterning outcomes when various molecular components of the bioelectric system are altered by culture media. Model simulations accurately predicted multicellular Vmem patterns when one or more molecular components were altered, as quantitatively confirmed by a machine learning-based quantitative image pattern similarity analysis. In the second modeling analysis, a genome-scale computational model of the human metabolic network was expanded with additional descriptors to investigate how induced pluripotent stem cells reroute metabolic fluxes and achieved cell growth objectives during cardiomyocyte differentiation under various culture media compositions. This framework integrated transcriptomic, thermodynamic, kinetic, and proteomic and novel fluxosome constraints including transport exchange between the cytosol and extracellular environment. From a comparative analysis across multiple published studies and our own experimental validations, we observed that the combination of novel and previous model constraints was required to replicate experimental media-induced changes in metabolic network dynamics during pluripotency and hiPSC-cardiomyocyte (hiPSC-CM) differentiation. We extended this study to a novel media supplementation condition of glutamine and ascorbic acid and found that experimental extracellular flux assays supported the model-predicted improvements to metabolic respiration of iPSC-derived cardiomyocyte progenitor cells. In summary, these results collectively validate the potential for model-guided media design of engineered living systems using understanding of bioelectric and metabolic systems properties.

]]> Laura Paige 1 1680705058 2023-04-05 14:30:58 1680705058 2023-04-05 14:30:58 0 0 event BioE PhD Defense Presentation- "Metabolic and Bioelectric Crosstalk in Directed Differentiation and Spatial Patterning of iPSC-derived Cardiomyocytes"- D. Andre Norfleet

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<![CDATA[BioE PhD Defense Presentation- Phoebe Welch]]> 27917 Advisors: Prof. Chengzhi Shi (Mechanical Engineering, Georgia Institute of Technology)

Prof. Craig R. Forest (Mechanical Engineering, Georgia Institute of Technology)

 

Committee:

Prof. Costas Arvanitis (Mechanical Engineering, Georgia Institute of Technology)

Prof. Brooks Lindsey (Biomedical Engineering, Georgia Institute of Technology)

Prof. Lilo D. Pozzo (Chemical and Biological Engineering, Univ. of Washington)

Prof. Levi Wood (Mechanical Engineering, Georgia Institute of Technology)

 

 

Ultrasound imaging of cells using gas vesicles and perfluorocarbon nanodroplets

 

Ultrasound imaging greatly benefits from the use of contrast agents to highlight regions of the body that typically exhibit low contrast. While gas microbubbles are the primary ultrasound contrast agent for certain medical imaging applications, they cannot be used for intracellular imaging because of their limited stability in physiological conditions. This thesis investigates two newer ultrasound contrast agents, gas vesicles and perfluorocarbon nanodroplets, that can be generated by cells or delivered intracellularly for localization of a specific cell type or a particular cell, respectively. We first explore mammalian acoustic reporter genes (mARGs), which enable gas vesicle expression in mammalian cells for localization in deep tissue. In Aim 1, we modify the original mARG construct to increase the proportion of cells that express gas vesicles by making the genes drug selectable, simplifying the process of creating a gas vesicle-expressing cell line with high ultrasound contrast. While mARGs are useful for imaging cell populations, the resulting gas vesicles do not produce sufficient ultrasound contrast to identify individual cells.  To achieve ultrasonic single cell localization, we shift our focus to PFCnDs. In Aim 2, we examine the lipid shell composition of PFCnDs to find an optimal ratio of lipid components that enable PFCnDs to generate ultrasound contrast with reduced risk of cell damage. In Aim 3, we microinject HEK293T cells with PFCnDs using patch clamp, noting the time and pressure parameters that result in successful nanodroplet injection, and demonstrate ultrasonic single-cell localization using this technique. These dissertation studies advance the use of both gas vesicles and perfluorocarbon nanodroplets as intracellular ultrasound contrast agents for various applications of cellular imaging.

]]> Laura Paige 1 1680100493 2023-03-29 14:34:53 1680100493 2023-03-29 14:34:53 0 0 event BioE PhD Defense Presentation- "Ultrasound imaging of cells using gas vesicles and perfluorocarbon nanodroplets"-  Phoebe Welch

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<![CDATA[BioE PhD Defense Presentation- Saeyoung Sunny Kim]]> 27917 Advisor: Brooks D. Lindsey (Georgia Institute of Technology and Emory University)

 

Committee:

Stanislav Emelianov (Georgia Institute of Technology and Emory University)

Alessandro Veneziani (Emory University)

John Oshinski (Georgia Institute of Technology and Emory University)

Costas D. Arvanitis (Georgia Institute of Technology and Emory University)

 

 

Development of a forward-viewing high frequency ultrasound for velocity and wall shear stress estimation in coronary arteries

 

Coronary artery disease is the most common type of cardiovascular disease, affecting > 18 million adults, and is responsible for > 365k deaths per year in the U.S. alone. Wall shear stress (WSS) is an indicator of likelihood of plaque rupture in coronary artery disease, however, non-invasive estimation of 3D blood flow velocity and WSS in coronary arteries is challenging due to the requirement for high spatial resolution at high penetration depths. For this reason, a catheter-based forward-viewing intravascular ultrasound (FV IVUS) imaging system is being developed to estimate real-time 3D velocity fields in patients already undergoing minimally-invasive diagnostic procedures in the cardiac catheterization lab. A novel WSS estimation technique was developed for a forward-viewing high frequency ultrasound array transducer in a coronary artery. Specific outcomes were: 1) Two different ultrasound-based blood flow velocity estimation approaches (Doppler and echo PIV) and resulting WSS estimates were compared in a patient-specific coronary artery geometry. 2) Motion-compensated blood flow velocity and WSS estimation techniques were developed to accurately estimate blood flow velocity and WSS in the presence of dynamic cardiac motion. 3) Developed blood flow velocity and WSS estimation techniques were demonstrated in the coronary artery of an ex vivo beating pig heart. Approaches for characterizing the coronary hemodynamic environment in 2D and 3D using forward-viewing, high frequency ultrasound transducer were developed and demonstrated for use in a catheter-based device. Future work will include in vivo validation of velocity and WSS estimation techniques using catheter-based FV IVUS imaging system.

]]> Laura Paige 1 1680100345 2023-03-29 14:32:25 1680100345 2023-03-29 14:32:25 0 0 event BioE PhD Defense Presentation- "Development of a forward-viewing high frequency ultrasound for velocity and wall shear stress estimation in coronary arteries" - Saeyoung Sunny Kim

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<![CDATA[BioE PhD Defense Presentation- Breandan Yeats]]> 27917 Advisor: Lakshmi Prasad Dasi, PhD (Georgia Institute of Technology) 

Committee Members: 

Ajit P. Yoganathan, PhD (Georgia Institute of Technology) 

John Oshinski, PhD (Georgia Institute of Technology and Emory University) 

Rudolph Gleason, PhD (Georgia Institute of Technology)

Vinod H. Thourani, MD (Piedmont Heart Institute) 

Biomechanics of Transcatheter Aortic Valve Replacement for Bicuspid Aortic Valves

Bicuspid aortic valve (BAV) is the most common congenital heart defect and is associated with numerous pathologies including calcific aortic valve disease (CAVD) which requires replacement of the native valve. Replacements are delivered through either surgical or transcatheter aortic valve replacement (TAVR) approaches. The number of TAVR in BAV cases is expected to increase substantially due to the recent removal of the FDA precautionary label for TAVR use in BAV patients and deemed safe in low-surgical risk patients. Two of the main concerns when treating BAV patients with TAVR are paravalvular leak (PVL), a known associate of increased patient mortality, and long-term durability. Highly calcified BAV patients have shown increased incidence of PVL following TAVR. Additionally, stent asymmetry and undersizing are common in BAV patients both being indicators of reduced device durability however, very limited data exists on TAVR long-term durability in BAV patients. Determining the risk of these complications based on BAV anatomy is very difficult as current morphology classification systems do not encompass all aspects of the anatomy and there is limited data correlating anatomy to these outcomes beyond calcium scoring. The impact of device placement and balloon filling volume across varying BAV anatomies is also not fully understood. The studies contained within this thesis document aim to contribute to answering these clinical unknowns with the overarching goal of better understanding TAVR biomechanics in BAV patients.

The first aim details a study in which the aortic valve and aortic arch were parametrically quantified and a classification framework was developed for each. The aortic valve was classified based on the commissure orientation and characteristics of the fused region. The aortic valve was classified based on the severity of local area changes and high curvature in the ascending and descending aorta. In the second aim, simulation models of the stent deployment, bioprosthetic leaflet pressurization, and PVL were developed and used to assess the deformation and integral portions of the device functionality following simulated patient-specific device implantation. Analysis of patient cohorts of BAV and trileaflet patients revealed BAV patients to have worsened device deformation and leaflet functionality. BAV patients that had excessive calcification or abnormal anatomies lead to the worst outcomes. Several mechanisms for PVL were found which were caused by non-symmetric features of the BAV anatomy including local vessel enlargements and calcification. In the third aim, varying TAVR strategies were tested. Lower balloon filling volume led to worsened device deformation and leaflet functionality and increased PVL. No structural impact was found with varying deployment depth. PVL was reduced with a higher deployment depth. Finally, clinical translation of the developed models was demonstrated through model use to guide clinical planning of TAVR treatment for a BAV patient with an extremely large annulus. The outcomes of this thesis can help clinicians better analyse BAV anatomy, select BAV patients for TAVR, and choose optimal TAVR strategies when treating BAV patients.

]]> Laura Paige 1 1680100192 2023-03-29 14:29:52 1680100192 2023-03-29 14:29:52 0 0 event BioE PhD Defense Presentation- "Biomechanics of Transcatheter Aortic Valve Replacement for Bicuspid Aortic Valves" - Breandan Yeats

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<![CDATA[BioE PhD Proposal- Farbod Sedaghati]]> 27917 Advisors:

Rudolph L. Gleason, Ph.D. (ME, Georgia Tech) 

Committee:

Brandon Dixon, Ph.D. (ME, Georgia Tech)

Alexander Alexeev, Ph.D. (ME, Georgia Tech)

Susan Thomas, Ph.D. (ME, Georgia Tech)

Luke Brewster, MD.  (School of Medicine, Emory University)

 

1-D Mathematical Modeling to Study the Mechanics of Pregnancy and Preeclampsia, Lymphedema, and Peripheral Arterial Disease

Mathematical modeling, along with experimental tools, has demonstrated promising strategies in understanding, diagnosing, and treating pathophysiological conditions. Among different modeling approaches, wave propagation models, including 1-dimensional solid-fluid interaction models, have presented acceptable outcomes when compared to clinical or experimental data. In that regard, we will utilize a 1-D modeling approach along with other accepted paradigms, such as those applied in arterial wall mechanics, including growth and remodeling mechanisms and vasoactive responses, to study some aspects of three common human complications, including preeclampsia, lymphedema, and peripheral artery disease (PAD). The significance of this combined study is that these complications together affect more than 10% of the US population each year. For each physiological condition, a modeling framework will be developed based on fundamental physics laws and other governing equations, such as wall mechanics. Following the development of the model for each condition and based on the nature of the problem, available data sources, and accessibility of experimental methods, a practical technique or procedure will be used to validate the mathematical model. Thus, by the end of the study, three mathematical models that correspond to each physiological condition, along with the validation dataset, will be provided that most likely will shed light on the progression of each complication. For example, to develop the mathematical model of PAD, we will perform a ligation surgery on the femoral arteries of a mouse model and track the hemodynamic and vascular changes due to the controlled PAD conditions. This can be extrapolated to human studies to design better experiments to understand the PAD.

]]> Laura Paige 1 1678306505 2023-03-08 20:15:05 1678306505 2023-03-08 20:15:05 0 0 event BioE PhD Proposal- "1-D Mathematical Modeling to Study the Mechanics of Pregnancy and Preeclampsia, Lymphedema, and Peripheral Arterial Disease" Farbod Sedaghati

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<![CDATA[BioE PhD Defense Presentation- Rebecca Schneider]]> 27917 Advisor: 

Andrés J. García, PhD (Georgia Institute of Technology)

 

Committee Members:

John Blazeck, PhD (Georgia Institute of Technology)

Wilbur A. Lam, MD, PhD (Emory University and Georgia Institute of Technology)

Ankur Singh, PhD (Georgia Institute of Technology)

Ross Marklein, PhD (University of Georgia)

 

High-throughput 3D on-chip potency assay for improved cell therapy product clinical prediction

 

Cell therapies offer promising strategies to treat diverse oncologic, inflammatory, and immune applications. Despite promising early phase clinical data, cell therapy candidates face new translational challenges, in part, due to a poor understanding of the cell therapy product during drug development and scale up. Current potency testing is often overly simplified and strongly biased by traditional 2D culture techniques. By engineering improved, well-defined, physiological-relevant in vitro systems, we aim to provide high-throughput and reproducible potency assays with improved outcome prediction of in vivo and/or clinical response. We have demonstrated proof-of-concept of the on-chip platform by showing improved in vitro immunomodulatory prediction and stronger fidelity to in vivo secretion compared to traditional 2D culture for n=9 mesenchymal stem/stromal cell (MSC) donors. We have further evaluated n=60 MSC and MSC-derivative clinical samples using the on-chip platform and found secretion outcomes with greater correlation and/or variance across donor-matched characteristics compared to 2D culture secretion. Future work will include platform clinical validation by evaluation of on-chip secretion correlation to patient-matched outcomes. The data presented here is in strong support of the value of the on-chip system to deliver scalable and high throughput cell product secretion information more predictive of in vivo and/or clinical settings.

]]> Laura Paige 1 1676387326 2023-02-14 15:08:46 1676387326 2023-02-14 15:08:46 0 0 event BioE PhD Defense Presentation- "High-throughput 3D on-chip potency assay for improved cell therapy product clinical prediction" -Rebecca Schneider

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<![CDATA[BioE PhD Proposal Presentation- Carla Kumbale]]> 27917 Advisors: Eberhard O. Voit, Ph.D. (BME, Georgia Tech & Emory University)

                 Qiang Zhang, Ph.D. (Environmental Health, Emory University)

 

Committee:

Melissa L. Kemp, PhD (BME, Georgia Tech & Emory University)

Peng Qiu, Ph.D. (BME, Georgia Institute of Technology and Emory University)  

Mark P. Styczynski, Ph.D.  (ChBE, Georgia Institute of Technology)

 

Assessing the Impact of Dioxin on Human Health through Mathematical Modeling

Exposure to persistent organic pollutants (POPs) can cause a variety of adverse health effects. Lipophilic POPs like dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD) are particularly harmful over a long time horizon because they can remain in fatty tissue for several decades after exposure. TCDD has been demonstrated to impact several organs, including the liver, which is considered the primary organ for detoxifying the effects of environmental contaminants and other xenobiotics. It is known that short-term exposure to high levels of dioxin may result in the development of skin lesions such as chloracne. Long-term exposure is associated with the impairment of cholesterol dynamics and reproductive functions.  Moreover, chronic dioxin exposure has been demonstrated to pose an immensely increased risk of developing diabetes and various cancers, often in the form of soft-tissue sarcoma, non-Hodgkin lymphoma, chronic lymphocytic leukemia, and liver cancer.

Due to the ubiquity of dioxins, all people worldwide have background exposure and a certain level of dioxins in the body. Given the high toxic potential of this class of compounds, efforts need to be undertaken to reduce current background exposure and counteract their effects. Many of the individual contributions of the impact of TCDD on human health have been documented in a host of toxicological studies. However, a comprehensive understanding of the overall impact of TCDD on the human body is required to develop countermeasures against these toxic effects.

In this dissertation I propose a computational multi-scale approach, using a “template-and-anchor” model that permits a valid integration of the various contributions of TCDD toward meaningful health risk assessments. Generically, a template is a high-level model that focuses exclusively on the main physiological components of a system and involves correspondingly few parameters and variables. It provides a coarse-grained representation of the system under investigation. Anchor models provide more elaborate views of the specific biological details characterizing the mechanisms that govern the system and are represented in the template model. Specifically, I will create a template model along with a collection of pertinent anchor models. Once the specific mathematical structure of these models is established, I will demonstrate how different concentrations of TCDD drive the input and output of each anchor model and, subsequently, the overarching template model. The overall objective of this proposal is to: (1) elucidate details of dioxin-induced changes in cholesterol dynamics (2); model the TCDD-induced effects on endocrine hormones such as estradiol to understand the mechanism by which dioxin exposure may contribute to diseases such as endometriosis; and (3) integrate all anchor models into a comprehensive template model that will allow us to assess the global effects of dioxin on the human body. The results of this work are hoped to be translatable into an overall–and possibly even personalized–human health risk assessment.

]]> Laura Paige 1 1676387207 2023-02-14 15:06:47 1676387207 2023-02-14 15:06:47 0 0 event BioE PhD Proposal Presentation- "Assessing the Impact of Dioxin on Human Health through Mathematical Modeling" -Carla Kumbale

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<![CDATA[BioE PhD Defense Presentation- Shelley Gooden]]> 27917 Advisor: Lakshmi Prasad Dasi, PhD (Georgia Institute of Technology) 

 

Committee Members

Ajit P. Yoganathan, PhD (Georgia Institute of Technology) 

Brandon Dixon, PhD (Georgia Institute of Technology) 

Mani A. Vannan, MD (Piedmont Heart Institute) 

Vinod H. Thourani, MD (Piedmont Heart Institute) 

Konstantinos D. Boudoulas, MD (The Ohio State University) 

   

Predicting Hemodynamic and Biomechanical Implications of MitraClip Transcatheter Edge-To-Edge Therapy on Treatment of Functional Mitral Regurgitation 

  

Mitral regurgitation (MR) is the leading cause of heart valve disease, where moderate MR is present in at least 1.7% of the adult population, increasing to 11.7% in those age 75 years and older. MR occurs when the two leaflets of the mitral valve (MV) do not close properly when they should. Left untreated, MR severity can increase and lead to heart failure. Patients with moderate-to-severe or severe MR who remain symptomatic despite optimal medical therapy and are deemed at high surgical risk by a heart team are candidates for transcatheter edge-to-edge repair with the commercially available MitraClip. Though clinical trials show promising outcomes, challenges with MitraClip use include sufficient reduction of MR while preventing elevated MV pressure gradient (MVG), as these two unfavourable outcomes worsen prognosis. Optimal use and predictive modeling of MVG post-MitraClip is not well defined, especially with four device sizes available in the current G4 generation. Further guidelines to optimize MitraClip usage is needed, as transcatheter MV repair has overtaken surgical repair in the United States. Impact of MitraClip size was first assessed using an excised porcine ventricular functional MR model, where residual regurgitation with device size was found to be dependent upon baseline MR conditions, and post-therapy MVG was found to increase most with the largest device size. A parameterization approach was developed to simplify human MV geometries, and MitraClip placement was simulated. Post-therapy MVG was found to be greatest for smaller MVs and for larger device size. Forward flow measured by clinical means (CW Doppler) and by the engineering means (conservation of mass) showed strong correlation. Applying this in vivo, a post-therapy MVG predictive model was developed, which showed good agreement to in vivo outcomes. The outcomes of this thesis can help clinicians assess patient MitraClip candidacy and help optimize MitraClip treatment strategies by predicting post-therapy MVG. 

]]> Laura Paige 1 1675264922 2023-02-01 15:22:02 1675264922 2023-02-01 15:22:02 0 0 event BioE PhD Defense Presentation- "Predicting Hemodynamic and Biomechanical Implications of MitraClip Transcatheter Edge-To-Edge Therapy on Treatment of Functional Mitral Regurgitation " - Shelley Gooden

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<![CDATA[BioE PhD Proposal Presentation- Liana Hatoum]]> 27917 Advisors: Manu O. Platt, Ph.D. (BME, Georgia Tech & Emory University)

                 Edward A. Botchwey, Ph.D. (BME, Georgia Tech & Emory University)

 

Committee:

Spencer H. Bryngelson, Ph.D. (College of Computing, Georgia Tech)

Rudolph L. Gleason, Ph.D. (ME, Georgia Tech)

John N. Oshinski, Ph.D. (BME, Georgia Tech & Emory University)

Alessandro Veneziani, Ph.D. (Mathematics, Emory University)

 

Longitudinal Magnetic Resonance Angiography to Quantify Arterial Remodeling in Sickle Cell Disease

 

Sickle cell disease (SCD) is a genetic blood disorder affecting 100,000 Americans. People living with SCD experience deteriorating disease progression with accelerated damage to carotid and cerebral arteries occurring as early as 2 years old. 11% of children with SCD suffer an overt stroke and 37% will suffer a silent stroke. Hematopoietic stem cell transplant (HSCT) is currently the only known cure for SCD. Children may continue to be at risk for strokes and other complications after HSCT. The pathogenesis of how arterial damage is initiated, and progresses is not fully understood. Recent studies have shown using a humanized sickle cell transgenic mouse model that cathepsin K, a powerful protease, is upregulated in SCD and mediates elastin and collagen degradation in the arterial wall. In those studies, expansive remodeling was observed in the common carotid arteries associated with aneurysms and weakened artery mechanics. The central hypothesis of this proposal is that chronic inflammation in SCD stimulates cathepsin K overexpression leading to pathological expansive arterial remodeling that can cause accelerated progression of aneurysms and hemorrhagic strokes.

To analyze the mechanisms that cause arterial damage in SCD, a combination of both in-vitro and in-silico studies will be used to investigate the morphology and hemodynamics of carotid arteries in mice with SCD. In this longitudinal study, a label free magnetic resonance angiography method will be used for the quantification of morphological changes to carotid and cerebral arteries in SCD mice as they age thereby reducing subject variability.  The objective of this proposal is to use magnetic resonance angiography to (1) determine the role of cathepsin K in expansive arterial remodeling using sickle cell transgenic mice genetically null for cathepsin K, (2) determine the effect of curative HSCT in preventing arteriopathy in SCD, and (3) identify pathological fluid flow profiles that would indicate arterial damage in SCD in an age-dependent manner. This research will provide a foundation for understanding cathepsin-mediated arterial remodeling and to determine why arterial damage persists in some patients after HSCT. These studies will potentially help develop novel therapies to prevent arteriopathy and strokes in SCD.

]]> Laura Paige 1 1673286509 2023-01-09 17:48:29 1673286509 2023-01-09 17:48:29 0 0 event BioE PhD Proposal Presentation-  "Longitudinal Magnetic Resonance Angiography to Quantify Arterial Remodeling in Sickle Cell Disease" Liana Hatoum

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<![CDATA[BioE PhD Defense Presentation- Dan Y. Zhang]]> 27917 Advisor:

Melissa L. Kemp, PhD (BME, Georgia Tech & Emory University)

 

Committee Members:

Wilbur A. Lam, MD, PhD (BME/Pediatrics, Georgia Tech & Emory University)

Manu O. Platt, PhD (BME, Georgia Tech & Emory University)

David K. Wood, PhD (BME, University of Minnesota)

Levi B. Wood, PhD (ME, Georgia Tech)

 

 

Informing Precision Medicine Through Data-driven Modeling of Patient-Specific Therapeutic Responses in Microfluidic-based Assays

 

The goal of precision medicine is to provide optimal treatment to patients based on their individual characteristics or disease state. Current genomic-based approaches are limited by the amount of patient sample needed, high turnaround time, and reliant on reported mechanisms of drug action and patient response. Microfluidic devices provide a way to directly and efficiently test small quantities of patient samples for functional outcomes; these devices can incorporate features such as the cellular environment to better model physiological variables. Turning microfluidics-derived data into actionable precision medicine insights requires collaboration between the fields of microsystems engineering, computational biology, and clinical medicine. On the computational side, novel data analysis pipelines and interpretable statistical modeling methods are needed to extract the maximal amount of information from microfluidics data and to generate clinically actionable insights.

 

The objective of this work was to leverage computational and mathematical approaches to develop robust predictive models of patient sample response assayed in microfluidic devices. This approach was validated using microfluidics-generated datasets from two hematologic applications: combination drug screening in leukemia, and rheological biomarker correlation in sickle cell disease. Specific outcomes were: 1) development of an analytical pipeline that measures drug synergy and efficacy metrics for combinations used in leukemia, 2) identification of a subpopulation of patients with sickle cell disease that may benefit from a novel therapy, and 3) correlation of microfluidic-based rheological metrics to symptomatic severity in patients with sickle cell disease. Overall, this work demonstrates the ability of the combined experimental-computational frameworks to extract important patient-specific features from multi-factorial experiments, optimize discovery of synergistic drug interactions, and provide personalized recommendations for therapy.

 

]]> Laura Paige 1 1669915377 2022-12-01 17:22:57 1669915377 2022-12-01 17:22:57 0 0 event BioE PhD Defense Presentation-"Informing Precision Medicine Through Data-driven Modeling of Patient-Specific Therapeutic Responses in Microfluidic-based Assays" -  Dan Y. Zhang

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<![CDATA[BioE PhD Proposal- Mercedes Gonzalez]]> 27917 Advisors: Craig Forest, Ph.D. (Mechanical Engineering) 

                   Matthew Rowan, Ph.D. (Biological Sciences, Emory)

  

Committee Members: 

Annabelle Singer, Ph.D. (Biomedical Engineering) 

Christopher Rozell , Ph.D. (Electrical and Computer Engineering) 

Bilal Haider, Ph.D. (Biomedical Engineering) 

  

Automated cellular electrophysiology to investigate the role of interneurons in Alzheimer's Disease  

 

Alzheimer's disease (AD) is the leading cause of dementia, affecting millions of people worldwide each year. AD is characterized by progressive decline in cognition and memory, often detected late in disease progression. A prevailing theory of AD has been that cognitive decline and memory loss is caused by progressive deposition of toxic amyloid and tau proteins. While significant efforts have been made to elucidate mechanisms behind these symptoms based on this idea, effective therapies remain elusive. An alternative hypothesis is that cognitive loss in early AD results from neuronal circuit dysregulation. In particular, parvalbumin-expressing (PV) interneurons are prone to changes in excitability in AD which contributes to circuit dysfunction. However, the spatiotemporal evolution of interneuron dysregulation throughout the brain is unclear. In addition, recent studies have found that 40 Hz optogenetic stimulation of PV-interneurons activates microglia and reduces amyloid beta load in aged AD mice, further supporting the idea that interneuron dysregulation plays a key role in AD progression. They also found that non-invasive light stimulation at 40 Hz effectively mitigated amyloid beta load in aged AD mice. This non-invasive therapeutic approach, however, is not yet thoroughly studied and lacks cell-type-specific characterization. In particular, the role of PV-interneurons in this phenomenon is not yet clear. Studying the intrinsic physiological properties of these PV-interneurons requires patch clamp electrophysiology, a time intensive and low-throughput neuroscience technique which allows one to record sub-threshold current and voltage membrane changes from individual neurons. Recent advances in the field of patch clamp have automated this laborious process; however, there are still bottlenecks that limit the throughput and yield. Thus, the objective of this proposal is to (1) optimize and leverage automated patch clamp electrophysiology, subsequently (2) explore the spatiotemporal emergence of PV-interneuron dysfunction in AD, and (3) investigate and quantify the effects of 40 Hz light and sound sensory stimulation on PV-interneurons in AD. 

]]> Laura Paige 1 1669731358 2022-11-29 14:15:58 1669731358 2022-11-29 14:15:58 0 0 event BioE PhD Proposal- "Automated cellular electrophysiology to investigate the role of interneurons in Alzheimer's Disease  " - Mercedes Gonzalez

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<![CDATA[BioE PhD Proposal- Nathan Zavanelli]]> 27917 Advisor: Woonhong Yeo, Ph.D. (Mechanical and Biomedical Engineering) 

  

Committee Members: 

Todd Sulchek, Ph.D. (Mechanical Engineering) 

Rudolph Gleason , Ph.D. (Mechanical Engineering) 

Omer Inan, Ph.D. (Electrical and Computer Engineering) 

Pamela Bhatti, Ph.D. (Electrical and Computer Engineering) 

  

Study of Soft Materials, Skin-like Device Mechanics, and Nano-Microfabrication to Develop Flexible Wearable Physiological Monitors for Advanced Diagnostics

  

The central focus of this research is the development of skin-like wearable electronics and sensors that seamlessly integrate with the human body and provide hospital quality physiological monitoring and diagnostics in a simple, minimally obtrusive platform. One of the most poignant tragedies in modern medicine is that many pathologies with highly effective treatments remain undiagnosed, especially in marginalized communities. This suffering is fueled by a systemic failure in current diagnostics techniques: one the one hand, hospital grade in lab tests are expensive, low throughput, and ill-suited for continuous monitoring; on the other, wearable electronics are fundamentally limited by rigid mechanics and wired interfaces that prevent conformal skin contact, producing poor signal quality and degraded long-term wearability. To address this critical shortcoming, this work consists of analytical, computational, empirical, and human subjects studies in soft materials and interfaces to enable a new class of wearable, wireless devices and sensors with mechanics finely tuned to transduce electrical, mechanical, and optical bio-signals from the human body, providing advanced diagnostic solutions to tackle some of the most pressing medical diagnostics challenges, both here in the United States and around the world.

]]> Laura Paige 1 1669731255 2022-11-29 14:14:15 1669731255 2022-11-29 14:14:15 0 0 event BioE PhD Proposal- "Study of Soft Materials, Skin-like Device Mechanics, and Nano-Microfabrication to Develop Flexible Wearable Physiological Monitors for Advanced Diagnostics" -Nathan Zavanelli

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2022-12-08T11:30:00-05:00 2022-12-08T13:30:00-05:00 2022-12-08T13:30:00-05:00 2022-12-08 16:30:00 2022-12-08 18:30:00 2022-12-08 18:30:00 2022-12-08T11:30:00-05:00 2022-12-08T13:30:00-05:00 America/New_York America/New_York datetime 2022-12-08 11:30:00 2022-12-08 01:30:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Proposal Presentation- Rachel Ringquist]]> 27917 Advisor: Krishnendu Roy, PhD (Biomedical Engineering)

 

Committee Members:

Ankur Singh, PhD (Mechanical Engineering)

Hang Lu, PhD (Chemical and Biomolecular Engineering)

Ahmet Coskun, PhD (Biomedical Engineering)

Rabin Tirouvanzium, PhD (Department of Pediatrics, Emory University)

 

An immune-competent microvascularized human lung-on-chip device for studying immunopathologies of the lung

 

Advances in microphysiological organ-on-chip technologies have enabled spatiotemporal investigation into the complex physiology of organ systems in healthy and disease-like conditions in vitro. The highly-tunable nature of on-chip models permit direct manipulation of the microenvironment and provides the framework to study disease progression in ways not feasible through other in vitro models or through in vivo animal models. Organ-on-chip models encompass cellular heterogeneity and structural organization that mimics an in vivo organ microenvironment, while still allowing for real-time, cellular-level spatial and temporal analysis. While organ-on-chip systems are becoming increasingly popular, there remains a disconnect between in vitro models of the immune system and organ-on-chip models, with very few organ-on-chips incorporating immune components. Immune dysregulation is a hallmark of nearly all disease states and thus the ability to model immune signals in vitro is paramount for the development of effective therapeutics.

We aim to address this knowledge gap through the development of an immune-competent, fully microvascularized, microfluidic human lung-on-chip device. Our overall hypotheses are (1) incorporation of tissue-resident macrophages and circulating immune cells into a lung-on-chip model will enable the recapitulation of hallmark immune dysfunction in an influenza A (H1N1) infection model and (2) development of the human lung disease model will allow identification of key drivers of disease-specific immune dysregulation and illuminate potential immunomodulatory therapies. The proposed specific aims to test these hypotheses are to (1) develop an immune-competent lung-on-chip device with tissue-resident and circulating immune populations and (2) develop and characterize viral infection in a lung-on-chip model using H1N1-induced immune activation. To date, we have demonstrated the successful incorporation of tissue-resident macrophages and circulating immune cells into a microvascularized, human lung-on-chip device. Furthermore, we have evaluated the role of tissue-resident macrophages in the immune response to H1N1 infection. Future work aims to identify key circulating immune cells involved in the response to H1N1 infection and identify potential avenues for immunomodulatory therapies. The in vitro immune response will be fully characterized using single cell RNA sequencing, flow cytometry, multiplexed cytokine analysis, and spatial-omics techniques, and the resulting information will be used to inform treatment strategies.

]]> Laura Paige 1 1667924413 2022-11-08 16:20:13 1667924413 2022-11-08 16:20:13 0 0 event BioE PhD Proposal Presentation- "An immune-competent microvascularized human lung-on-chip device for studying immunopathologies of the lung" - Rachel Ringquist

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2022-11-14T15:30:00-05:00 2022-11-14T17:30:00-05:00 2022-11-14T17:30:00-05:00 2022-11-14 20:30:00 2022-11-14 22:30:00 2022-11-14 22:30:00 2022-11-14T15:30:00-05:00 2022-11-14T17:30:00-05:00 America/New_York America/New_York datetime 2022-11-14 03:30:00 2022-11-14 05:30:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[MS Thesis Presentation- Sydney Wimberley]]> 27917 Advisor:               Julie Champion, PhD 

 

Committee:        Manu Platt, PhD

Mark Prausnitz, PhD

 

 

Engineering Bovine Serum Albumin Nanoparticles for Improved Endosomal Escape and The Treatment of Endometriosis

Endometriosis is an estrogen driven condition that affects about 10% of menstruating women. It causes severe pain and infertility, and limited treatment options are available. This work uses the anti-inflammatory protein, AvrA, an effector protein found in Salmonella that inhibits nuclear factor-kB (NF-kB) and mitogen-activated protein kinase (MAPK) signal cascades. However, this protein is highly insoluble and requires a carrier for delivery to the cytosol, and bovine serum albumin (BSA) nanoparticles are used to deliver AvrA. AvrA-BSA nanoparticles were delivered to End1/E6E7, an epithelial cell line derived from a woman’s endometrium with endometriosis. To measure functionality of AvrA-BSA nanoparticles, inflammatory cytokines were measured in this cell type under inflammatory conditions.

AvrA-BSA nanoparticles are internalized by cells using endocytosis. Their delivery to the cytosol is highly inefficient and endosome contents are trapped and later destroyed or recycled out of the cell following fusion with lysosomes, this is phenomenon is called endosomal entrapment. To overcome this entrapment, BSA nanoparticles were modified by conjugating histidine to their hydroxyl groups. Histidine’s variable chain is imidazole, and it can act as a buffer in lower pH environments, such as endosomes. In an endosome at lower pH protons and ions will enter the endosome causing them to swell due to a concentration gradient and an increase in osmotic pressure, eventually causes rupture. Endosomal escape of nanoparticles was evaluated using a Galectin-8 assay, to quantify endosomal disruption events; and a functional readout, where nanoparticles are loaded with toxic proteins allowing cell death to be an indication of nanoparticle escape. Overall, imidazole conjugated BSA nanoparticles do increase endosomal disruption events, and are able to incur an increased cell death when nanoparticles are loaded with a toxic protein.

]]> Laura Paige 1 1667924068 2022-11-08 16:14:28 1667924068 2022-11-08 16:14:28 0 0 event MS Thesis Presentation-  "Engineering Bovine Serum Albumin Nanoparticles for Improved Endosomal Escape and The Treatment of Endometriosis" - Sydney Wimberley

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2022-11-17T14:30:00-05:00 2022-11-17T16:30:00-05:00 2022-11-17T16:30:00-05:00 2022-11-17 19:30:00 2022-11-17 21:30:00 2022-11-17 21:30:00 2022-11-17T14:30:00-05:00 2022-11-17T16:30:00-05:00 America/New_York America/New_York datetime 2022-11-17 02:30:00 2022-11-17 04:30:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Proposal- Phoebe Welch]]> 27917 Advisors:

Prof. Chengzhi Shi – School of Mechanical Engineering

Prof. Craig Forest – School of Mechanical Engineering (co-advisor)

 

Committee:

Prof. Costas Arvanitis – School of Mechanical Engineering

Prof. Brooks Lindsey – School of Biomedical Engineering

Prof. Levi Wood – School of Mechanical Engineering

Prof. Lilo D. Pozzo – School of Chemical and Biological Engineering, University of Washington

 

 

Ultrasound imaging of deep tissue and cells using gas vesicles and perfluorocarbon nanodroplets

 

Ultrasound imaging is a technique that can be applied to a vast array of body systems thanks to its safety and versatility. However, there are still several drawbacks to ultrasound imaging, namely that the resolution pales in comparison to optical techniques (hundreds of micron resolution vs. hundreds of nanometer scale) and lacks any ability for long-term imaging with current commercially-available ultrasound contrast agents. As a result, there is a critical need for ultrasound contrast agents that can improve ultrasound resolution and enable long-term imaging for diagnostic applications, cell tracking, tissue graft monitoring, and more.

Two ultrasound contrast agents, perfluorocarbon nanodroplets and gas vesicles, have recently emerged and are becoming more commonplace in academic research. Perfluorocarbon nanodroplets are phase-change contrast agents that can extravasate into tumors via endothelial gaps in blood vessels and can remain in the body for days, enabling long-term imaging, but the use of these nanodroplets for single-cell imaging has yet to be explored. Gas vesicles are produced by certain cyanobacteria and archaea to help with buoyancy, and recent work has enabled gas vesicle expression in mammalian cells for prolonged periods of time using mammalian acoustic reporter genes (mARGs). However, these mARGs have only been integrated in certain cell lines, and the methods to isolate cells that successfully express gas vesicles are complex. These two nanoscale ultrasound contrast agents both have the potential to be used for deep tissue, high resolution, and long-term in vivo imaging, but require alterations to achieve this. This thesis proposal seeks to modify these ultrasound contrast agents and employ them for long-term, deep tissue imaging in vitro. For perfluorocarbon nanodroplets, I will optimize their  outer shell parameters to improve nanodroplet phase-transitioning, utilize patch clamping to isolating the nanodroplets in individual cells, monitor the long-term cell health to ensure the nanodroplets do not hinder cell viability, and ultrasonically image the nanodroplets injected into the cell within a gel tissue phantom. For the genetically expressed gas vesicles in mammalian cells, I will expand gas vesicle integration into other mammalian cells, specifically induced pluripotent stem cells, and simplify the procedures for generating gas vesicle-expressing mammalian cells using improved plasmids and drug selection techniques.

]]> Laura Paige 1 1664197980 2022-09-26 13:13:00 1664197980 2022-09-26 13:13:00 0 0 event BioE PhD Proposal- "Ultrasound imaging of deep tissue and cells using gas vesicles and perfluorocarbon nanodroplets" - Phoebe Welch

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2022-10-07T15:00:00-04:00 2022-10-07T17:00:00-04:00 2022-10-07T17:00:00-04:00 2022-10-07 19:00:00 2022-10-07 21:00:00 2022-10-07 21:00:00 2022-10-07T15:00:00-04:00 2022-10-07T17:00:00-04:00 America/New_York America/New_York datetime 2022-10-07 03:00:00 2022-10-07 05:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Proposal- Nischita Kaza]]> 27917  

Advisor:

Francisco E. Robles, Ph.D. (Georgia Institute of Technology and Emory University)  

  

Committee Members:  

Ahmet F. Coskun, Ph.D. (Georgia Institute of Technology and Emory University School of Medicine)   

Peng Qiu, Ph.D. (Georgia Institute of Technology and Emory University)  

Thomas K. Gaylord, Ph.D. (Georgia Institute of Technology)   

Wilbur A. Lam, M.D., Ph.D. (Georgia Institute of Technology and Emory University School of Medicine)   

 

Simple, high-resolution molecular imaging for biological and clinical applications via label-free Deep ultraviolet microscopy

 

    Imaging with deep ultraviolet (~200 - 400 nm) light enables label-free molecular imaging due to the distinctive absorption and dispersion properties of several physiologically important, endogenous biomolecules in this spectral region. In addition, the shorter wavelength of UV light offers higher spatial resolution than conventional imaging systems that use visible light. Furthermore, recent advances in UV light sources and detectors have resulted in simple, low-cost setups that enable contiguous imaging of live cells over long durations without significant photodamage. Therefore, deep-UV microscopy yields quantitative molecular and structural information from biological samples that can aid in monitoring or diagnosing diseases.  

      This proposal focuses on hyperspectral, multispectral, and single-wavelength deep-UV microscopy techniques for cellular phenotyping and analysis. We first develop methods to extract quantitative absorption information from biological samples using non-interferometric hyperspectral imaging and multispectral deep-UV microscopy and validate our approach using red blood cells. We then leverage recent advances in deep learning to realize a fully automated pipeline for label-free hematology analysis using single-wavelength UV microscopy images. The results of this work can pave the way for low-cost, label-free imaging systems for use in clinical, at-home, and point-of-care settings. Finally, we propose a UV microscopy system capable of 3D live cell imaging with molecular specificity, which would not only provide unique biological insights but also enable robust cell phenotyping and disease diagnosis. 

]]> Laura Paige 1 1664197861 2022-09-26 13:11:01 1664197861 2022-09-26 13:11:01 0 0 event BioE PhD Proposal- "Simple, high-resolution molecular imaging for biological and clinical applications via label-free Deep ultraviolet microscopy " - Nischita Kaza

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<![CDATA[BioE PhD Proposal- Jihoon Lee]]> 27917 Advisor: 

Shuichi Takayama, Ph.D.

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory School of Medicine

 

  

Committee Members:  

  

Stanislav Emelianov, Ph.D.

School of Electrical and Computer Engineering, Georgia Institute of Technology

 

M. G. Finn, Ph.D.

School of Chemistry and Biochemistry, Georgia Institute of Technology

 

Eric Sorscher, M.D.

Department of Pediatrics, Emory School of Medicine

 

Jason Spence, Ph.D.

Department of Cell and Developmental Biology, University of Michigan Medical School

 

Krishnendu Roy, Ph.D.

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory School of Medicine

 

 

Human airway organoids with reversed biopolarity for high-throughput anti-SARS-CoV-2 Compound Screening 

 

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19), has resulted in 6.5 million deaths worldwide since its emergence (as of 09/16/2022). Although slowed down in its pace thanks to the scientific advances achieved over the past two years, the virus remains a considerable threat. In a pressing demand for a rapid and efficient research tool for the ongoing pandemic, organoids have provided timely and powerful in vitro models to study viral tropism, host immune response, drug screening, and vaccine development. However, despite the immense number of research outputs, there have been varying and inconsistent results on host responses and pharmacodynamics, even within the same type of organoids. The observed variability may be attributed to challenging apical access in the conventional organoids, wherein the apical surface is sequestered away (“apical-in”) from the surrounding environment. Therefore, apical access is highly implicated, as it is the apical surface where the host-virus interactions predominantly occur. Our lab has recently demonstrated a high-throughput culture method of reproducible and uniform geometrically-inverted mammary epithelial organoids, in which the apical surface is stably oriented toward the organoid exterior (apical-out). The goal of the proposal is to adapt this method to human primary airway cells and utilise the resulting apical-out organoids as a high-throughput anti-SARS-CoV-2 compound screening platform. In Aim I, we will establish and optimise a culture of human bronchial epithelial organoids with reversed biopolarity (hBORBs). In Aim II, we will test and validate hBORBs as a high-throughput anti-SARS-CoV-2 compound screening platform. In Aim III, we will adapt the developed protocol to generate human nasal epithelial organoids with reversed biopolarity (hNORBs) derived from freshly isolated nasal epithelial cells.  

]]> Laura Paige 1 1663678245 2022-09-20 12:50:45 1663678245 2022-09-20 12:50:45 0 0 event BioE PhD Proposal-  "Human airway organoids with reversed biopolarity for high-throughput anti-SARS-CoV-2 Compound Screening " -Jihoon Lee

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2022-09-30T15:00:00-04:00 2022-09-30T17:00:00-04:00 2022-09-30T17:00:00-04:00 2022-09-30 19:00:00 2022-09-30 21:00:00 2022-09-30 21:00:00 2022-09-30T15:00:00-04:00 2022-09-30T17:00:00-04:00 America/New_York America/New_York datetime 2022-09-30 03:00:00 2022-09-30 05:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Proposal - Afsane Radmand]]> 27917 Advisor:  

James E. Dahlman, Ph.D. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University 

 

Committee Members: 

 

Philip J. Santangelo, Ph.D. 

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University 

 

Julie A. Champion, Ph.D. 

Department of Chemical and Biomolecular Engineering, Georgia Institute of Technology 

 

Wilber Lam, Ph.D.  

Department of Biomedical Engineering, Georgia Institute of Technology and Emory University 

 

Brandon Dixon, Ph.D. 

Department of Mechanical Engineering, Georgia Institute of Technology 

 

 

Next-generation lipid nanoparticle formulations for non-liver delivery of nucleic acid-based therapies and vaccines  

 

The clinical application of lipid nanoparticles (LNPs) delivering RNA therapies has advanced remarkably over the past few decades with the Food and Drug Administration (FDA) approval of ONPATTRO® in 2018 for treating liver genetic disease following systemic administration and the most recent COVID-19 vaccines developed by Moderna Therapeutics Inc. and Pfizer-BioNTech in 2021. Despite the success of first-generation LNP-RNA therapies, there still remains needs to rationally design next-generation LNP formulations for systemic non-liver delivery and for vaccination against other malignant diseases such as respiratory syncytial virus (RSV). In this work, we aimed to (i) identify helper lipid design rules and biological response for systemic lung mRNA delivery of LNPs, (ii) investigate the effect of cationic lipids in LNP formulation on systemic in vivo non-liver tropism, and (iii) develop a mRNA-based LNP vaccine for RSV. This work will establish the foundation towards two crucial objectives: (1) exploiting lipid nanoparticle design rules for systemic non-liver delivery of nucleic acid-based therapies (2) determining factors for LNP mRNA-based vaccine immunogenicity which will allow for taking a leap towards developing clinically relevant nucleic acid-based vaccines.  

]]> Laura Paige 1 1663170337 2022-09-14 15:45:37 1663170337 2022-09-14 15:45:37 0 0 event BioE PhD Proposal - "Next-generation lipid nanoparticle formulations for non-liver delivery of nucleic acid-based therapies and vaccines  " - Afsane Radmand

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<![CDATA[BioE PhD Defense Presentation- Michael Hunckler]]> 27917 Advisor:

Andrés García, PhD (Georgia Institute of Technology)

 

Committee Members:

Edward Botchwey, PhD (Georgia Institute of Technology)

Krishnendu Roy, PhD (Georgia Institute of Technology)

Ankur Singh, PhD (Georgia Institute of Technology)

Cristina Nostro, PhD (University of Toronto)

 

Synthetic Hydrogels for the Maturation and Engraftment of Stem Cell-Derived Beta Cells

 

Stem cell-derived β-cells are positioned to be a transformative cure for type 1 diabetes (T1D) by replacing the insulin-producing β-cells destroyed by the autoimmune system. Human induced pluripotent stem cells (hiPSCs) can differentiate into insulin-producing cells that phenotypically and functionally resemble immature β-cells. While promising, fully functional in vitro differentiation of these hiPSCs into mature β-cells remains elusive. Current in vitro differentiation protocols of hiPSCs cannot provide the precise microenvironmental cues necessary for complete maturation. Consequently, in vivo implantation is often used to direct end-stage maturation of stem cells, resulting in an uncontrolled environment to direct β-cell maturation. Furthermore, there are few suitable delivery vehicles for transplantation to clinically-translatable extrahepatic sites. These challenges highlight the need for strategies that enhance the in vitro maturation of the hiPSC-derived β-cells and improve their engraftment and function in a clinically-translatable transplant site. The objective of this project is to engineer advanced synthetic hydrogels to direct in vitro maturation of hiPSC-derived β-cells and enhance engraftment in an extrahepatic murine site. In Aim 1, I demonstrate that engineered synthetic hydrogels support the viability and differentiation of encapsulated hiPSCs to a mature β-cell stage. In Aim 2, I demonstrate that an engineered vasculogenic synthetic hydrogel supports the engraftment of pancreatic progenitors and immature β-cells into the mouse fat pad. In Aim 3, I develop a novel hydrolytic hydrogel that demonstrates tunable in vivo degradation kinetics to promote enhanced stem cell engraftment and vascularization. This project will provide a significant foundation for translation of hiPSC-derived β-cells into more clinically-relevant sites and establish innovative materials that promote survival, engraftment, and function of hiPSC-derived β-cells.

]]> Laura Paige 1 1661797213 2022-08-29 18:20:13 1661797213 2022-08-29 18:20:13 0 0 event BioE PhD Defense Presentation- "Synthetic Hydrogels for the Maturation and Engraftment of Stem Cell-Derived Beta Cells" - Michael Hunckler

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<![CDATA[BioE PhD Defense Presentation- Karen Martin]]> 27917 Advisor:

Andrés García, PhD (Georgia Institute of Technology)

 

Committee Members:

Edward Botchwey, PhD (Georgia Institute of Technology)

Levi Wood, PhD (Georgia Institute of Technology)

Nick Willett, PhD (University of Oregon)

Esma Yolcu, PhD (University of Missouri)

 

Hydrogel-delivery of mesenchymal stem cells to modulate the local immune environment and direct tissue repair

 

Mesenchymal stem/stromal cells (MSC) are actively being explored for use in a variety of regenerative medicine applications due to their potent immunosuppressive and anti-inflammatory properties. Traditionally, these cells have been delivered by bolus injection, but the need to prolong the survival and retention of MSC at sites of injury has spurred the development of a variety of biomaterial-based MSC delivery vehicles. Many studies have explored how biomaterial properties modulate MSC behaviors in both in vitro and in vivo contexts. However, a majority of the in vivo studies were carried out in immunocompromised mice, neglecting the key interaction of the host immune system with these biomaterial-MSC constructs. Additionally, while many properties of synthetic biomaterials are well-defined, controlling biomaterial degradation rates in in vivo environments remains a significant, therapeutic-limiting challenge. The objective of this thesis is to utilize immunocompetent mouse models to evaluate the immunomodulatory and regenerative effects of engineered biomaterial-MSC constructs. In Aim 1, I demonstrate that subcutaneous delivery of murine MSC within synthetic hydrogels in immunocompetent mice modulates the local cytokine milieu and temporal recruitment of immune cells to the hydrogel. In Aim 2, I show that, when delivered subcutaneously in a hydrogel, the fetal bovine serum used for ex vivo MSC expansion elicits a robust type 2 immune response characterized by infiltration of eosinophils and CD4+ T cells and that this immune response impairs bone repair. Finally, in Aim 3, I utilize hydrolytically degradable ester linkage groups to engineer PEG hydrogels with tunable in vivo degradation kinetics for enhanced delivery of MSC to diabetic cutaneous wounds. Overall, this work yields critical insights into MSC-immune cell interactions in vivo and highlights strategies for modulating these interactions through the use of engineered biomaterial MSC delivery vehicles.

]]> Laura Paige 1 1661020214 2022-08-20 18:30:14 1661020214 2022-08-20 18:30:14 0 0 event BioE PhD Defense Presentation- "Hydrogel-delivery of mesenchymal stem cells to modulate the local immune environment and direct tissue repair" - Karen Martin

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<![CDATA[BioE PhD Defense Presentation- Hannah Viola]]> 27917 Advisor:

Shuichi Takayama, Ph.D.

 

Committee Members:

Rabindra Tirouvanziam, Ph.D.

Jocelyn R. Grunwell, Ph.D., MD

Andres Garcia, Ph.D.

Hang Lu, PhD

 

Modeling Distal Pulmonary Physiology in Microphysiological Systems

 

      The distal airways can become obstructed and limit lung function in many pulmonary diseases, both acute and chronic. This small airway dysfunction results from aberrant mechanical forces, inflammatory mediators, abnormal fluid properties, and other factors. However, studying these contributions to small airway disease is challenging. Existing methods, such as biopsy of human tissue, animal models, and 2D in vitro models cannot reflect the dynamic processes of fluid-mediated injury and inflammation in the small airways with adequate precision and control. Therefore, in this Thesis I develop methods to model the small airways in vitro using microphysiological systems (MPS). MPS are complex cell culture models that capture functional aspects of the tissue in a human-cell based, controlled microenvironment. Here, I utilize microfluidic platforms and high throughput culture systems to recreate phenomena that contribute to small airway injury. In Aim 1, I demonstrate that fluid-mediated injury results in small airway epithelial cell death. In Aim 2, I develop a high throughput method for generation of small airway air-blood barrier mimetic microtissues that respond to viral exposure with epithelial-endothelial coordination. Finally, in Aim 3 I apply the air-blood barrier array (ABBA) to develop a standardized, high throughput method for modeling and studying the infiltration of neutrophils into the epithelial lumen. I demonstrate the model’s disease-mimetic capability and generate patient-specific dose-response curves for anti-inflammatory therapeutics. Overall, this Thesis contributes substantially to the field of lung-mimetic microphysiological systems and contributes novel applications of such systems for the investigation of complex contributors to small airway dysfunction.

]]> Laura Paige 1 1658944592 2022-07-27 17:56:32 1658944592 2022-07-27 17:56:32 0 0 event BioE PhD Defense Presentation- "Modeling Distal Pulmonary Physiology in Microphysiological Systems" - Hannah Viola

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<![CDATA[BioE PhD Defense Presentation- Dillon Brown]]> 27917 Advisors:

Machelle Pardue, Ph.D.

C. Ross Ethier, Ph.D.

 

Committee Members:

Rafael Grytz, Ph.D.

J. Brandon Dixon, Ph.D.

Wilbur Lam, MD, Ph.D.

 

An Investigation of Scleral Biomechanics and Myopia in the Mouse

The prevalence of myopia, or ”nearsightedness” is on the rise globally, set to affect about half of the global population by 2050. A myopic eye is characterized by a mismatch between the focal point of incoming light and the position of the photosensitive retina, most commonly due to excessive axial elongation of the eye (axial myopia). Axial myopia is thought to be driven by remodeling of the scleral microstructure and altered biomechanics. Certain types of visual cues drive or protect against myopigenic axial elongation, coupling retinal signaling to scleral remodeling via a complex ”retinoscleral” signaling cascade. However, the key signaling molecules that may propagate retinal signal(s) through the choroid to the sclera are largely unknown. All-trans retinoic acid (atRA) has been suggested to be both capable of trans-choroidal signaling and influencing scleral remodeling of glycosaminoglycans, biomechanically relevant extracellular matrix components known to change rapidly upon presentation of visual cues.

The mouse can be an excellent model organism for causal studies of myopigenesis, yet its small eye makes confirming axial elongation and scleral changes technically challenging. The central hypothesis of this work was that visual cues will lead to scleral remodeling and altered biomechanics comparable to other species. Additionally, we hypothesized that artificially increasing atRA concentration in the eye leads to a myopic phenotype.

To address these hypotheses, we developed a method to quantify the material properties of the mouse sclera using compression testing and a poroelastic material model, permitting the first characterizations of mouse scleral compressive/tensile stiffness and hydraulic permeability. In the mouse model of form-deprivation myopia, we then showed that the extensibility and permeability of the mouse sclera are greatly increased during myopigenesis, even without measurable axial elongation. We then characterized the ocular phenotype of mice treated with atRA, showing that atRA is myopigenic in the mouse and that scleral biomechanics are altered in a manner similar to that seen in visually mediated myopigenesis. These results implicate retinoic acid in the myopigenic retinoscleral signaling cascade and lay the groundwork for future studies of myopigenesis in the mouse.

]]> Laura Paige 1 1658936656 2022-07-27 15:44:16 1658936656 2022-07-27 15:44:16 0 0 event BioE PhD Defense Presentation- "An Investigation of Scleral Biomechanics and Myopia in the Mouse" - Dillon Brown

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<![CDATA[BioE MS thesis defense presentation- Fredrick Bulondo]]> 27917 Advisor:  

Julia E. Babensee, PhD | School of Biomedical Engineering, Georgia Institute of Technology. 

 

Committee: 

Susan Thomas, PhD | School of Mechanical Engineering, Georgia Institute of Technology. 

Stanislav Emelianov, PhD | School of Electrical & Computer Engineering, Georgia Institute of Technology. 

 

OPTIMIZATION OF IL-10 INCORPORATION FOR DENDRITIC CELLS Embedded IN PEG-4MAL HYDROGELS. 

 

Abstract 

Over the recent decades, translational research in biomaterials and immunoengineering has been appreciated by science, which is corroborated by the development of novel advanced therapies to treat cancer, autoimmunity, and other immune-related pathologies. Dendritic cells (DCs) have been at the core center of pharmaceutical and biological therapeutics as vital mediator of the immune system leveraging on its function to bridge the innate and adaptive immune system. This thesis focuses on developing a biomaterial system to ameliorate autoimmunity.  This biomaterial system is comprised of a poly (ethylene glycol)- 4 arms maleimide (PEG-4MAL) hydrogels conjugated with the immunosuppressive cytokine, interleukin, IL-10, which is injectable, in situ cross linkable and degradable system for localized delivery of immunosuppressive DCs. Studies conducted here aimed at optimizing the amount of IL-10 incorporated in hydrogel at 500ng concentration, which exhibited highest DC viability, immunosuppressive phenotype and protection against pro-inflammatory insult as compared to hydrogel-incorporated DCs at lower loading IL-10 amounts. Additionally, the studies addressed the optimization of degradability of the hydrogel to control the release rate of IL-10 from the gel, by varying the ratio of adhesive peptides: VPM (degradable) and DTT (non-degradable) peptide crosslinkers. The results obtained are promising and shall be significant for in vivo model optimization of immunosuppressive viability and functionality for incorporated DCs in cell delivery immunotherapy function. 

Henceforth, it important to incorporate optimal loading amounts of IL-10 with hydrogels embedding DCs because this immunosuppressive cytokine provides a tolerogenic environment that keeps DCs in their immature phenotype which consequently enhances cell viability and optimizes the system’s immune modulatory functionality.  

 

]]> Laura Paige 1 1658327134 2022-07-20 14:25:34 1658327134 2022-07-20 14:25:34 0 0 event BioE MS thesis defense presentation- "OPTIMIZATION OF IL-10 INCORPORATION FOR DENDRITIC CELLS EMBEDDED IN PEG-4MAL HYDROGELS. " - Fredrick Bulondo

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<![CDATA[BioE PhD Defense Presentation- Pawel Golyski]]> 27917 Advisor:  

Gregory S. Sawicki, Ph.D.  

  

Committee:  

T. Richard Nichols, Ph.D. (Georgia Institute of Technology)  

Lena H. Ting, Ph.D. (Georgia Institute of Technology, Emory University)  

Young-Hui Chang, Ph.D. (Georgia Institute of Technology)  

Keith E. Gordon, Ph.D. (Northwestern University)  

  

Tuning biomechanical energetics with an exoskeleton to improve stability during walking  

  

Exoskeletons are promising tools to improve multiple aspects of our daily lives – they can increase our strength, improve our efficiency during walking and running, and lower our risk of injury during tasks such as lifting. Further, passive exoskeletons with elastic elements can be lighter and cheaper than their motor-driven counterparts, while also being able to assist us by modulating the mechanics of muscles and biological joints. However, one critical aspect of locomotion which we do not understand the influence of passive exoskeletons on is stability. This overall project addresses the interaction between the areas of locomotion stability, muscle mechanics, and passive exoskeleton assistance through the lens of mechanical energetics with two principal aims: 1) to determine the multi-scale response to transient mechanical energy demands of proximal joints and muscles, and 2) to evaluate the influence of a passive hip exoskeleton on stability during perturbed walking. By addressing these aims, this work provides valuable initial insights into the role of proximal joints and muscles in responding to perturbations during walking in humans and establishes the potential of passive exoskeletons for improving stability in daily life. 

]]> Laura Paige 1 1656527266 2022-06-29 18:27:46 1656527266 2022-06-29 18:27:46 0 0 event BioE PhD Defense Presentation- "Tuning biomechanical energetics with an exoskeleton to improve stability during walking" - Pawel Golyski

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<![CDATA[BioE PhD Defense - Alejandro Da Silva Sanchez]]> 27917 Advisor:

James E. Dahlman, Ph.D. BME, Georgia Institute of Technology and Emory University 

 

Committee Members: 

 

Philip J. Santangelo, Ph.D. 

BME, Georgia Institute of Technology and Emory University 

 

Julie A. Champion, Ph.D. 

ChBE, Georgia Institute of Technology 

 

Mark P. Styczynski, Ph.D. 

ChBE, Georgia Institute of Technology 

 

MG Finn, Ph.D. 

Chemistry and Biochemistry, Georgia Institute of Technology

 

 

The impact of the metabolic state of a cell on nucleic acid therapeutics 

 

Nucleic acid therapies have advanced over the last decade with the FDA approval of the first siRNA drug in 2018 and the recent approval of COVID vaccines leveraging mRNA technology. While surface receptors and endocytosis genes have been shown to influence the effectiveness of RNA drug delivery with lipid nanoparticles (LNPs), the effect of the metabolic state of a cell upon therapies seeking to produce or silence proteins remains understudied. This project therefore aims to (i) understand whether metabolic perturbations to the mTOR pathway upon PIP3 extracellular administration affect LNP-mediated mRNA delivery, (ii) develop cell- and mouse-agnostic high throughput LNP screening systems for siRNA and mRNA drugs that will allow scientists to perform mechanistic studies on functional delivery with genetic knockout mice, and (iii) leverage these platforms to study whether cells exhibiting different levels of activity across the mTOR signaling pathway are more or less receptive to different nucleic acid drugs. This work will constitute early steps toward two equally important goals: (a) exploiting natural differences in cell signaling to improve cell type–specific nanoparticle delivery and (b) understanding how different physiological states can lead to different delivery potencies of nucleic acid therapeutics. 

 

]]> Laura Paige 1 1656341030 2022-06-27 14:43:50 1656341030 2022-06-27 14:43:50 0 0 event BioE PhD Defense -  "The impact of the metabolic state of a cell on nucleic acid therapeutics " - Alejandro Da Silva Sanchez

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<![CDATA[BioE MS Thesis Presentation- Victor Menezes]]> 27917  

Advisor:

Costas Arvanitis, PhD

 

Committee Members:

John McDonald, PhD

Levi Wood, PhD

 

 

Assessment of Chemotherapy Cytotoxic Activity in Brain Tumors with Cancer Soluble Biomarkers

 

 

Microbubble enhanced focused ultrasound (MB-FUS) is a promising minimally invasive technology for targeted drug delivery in brain tumors. As this technology is currently under clinical evaluation, methods to assess effective drug delivery and refine treatment protocols beyond the anatomical information (e.g., tumor size) provided by MRI are needed. In this study, we investigated the abilities of cancer soluble molecules to assess effective chemotherapy agent delivery in glioma tumors, track tumor growth, and confirm blood-brain and blood-tumor barrier (BBB/BTB) opening. We employed the glioblastoma cell line GL261 that was transfected to express the secretable bioluminescent molecule Gaussia luciferase (GLuc), which was used as a test molecule for assay development. We separately applied three different chemotherapeutic agents (Doxorubicin, Carboplatin, Temozolomide), which are currently in clinical trials in combination with MB-FUS and assessed the secretion of GLuc molecule and gene, using bioluminescence assay and PCR. Our analysis and quantification of soluble cancer biomarkers suggest that cfDNA can be employed to assess effective chemotherapy delivery to brain cancer, however these approaches might not be as effective with all types of chemotherapy. Further research to assess the potential of cfDNA to monitor effective chemotherapy delivery in brain tumors using MB-FUS is warranted.

]]> Laura Paige 1 1655776310 2022-06-21 01:51:50 1655776310 2022-06-21 01:51:50 0 0 event BioE MS Thesis Presentation- "Assessment of Chemotherapy Cytotoxic Activity in Brain Tumors with Cancer Soluble Biomarkers" - Victor Menezes

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<![CDATA[BioE PhD Defense- Yirui Li]]> 27917 Advisor:

Julie Champion, PhD

 

Committee Members:

Julie Champion, Ph.D.

Shuichi Takayama, Ph.D.

Ravi Kane, Ph.D.

Valeria Milam, Ph.D.

James Dahlman, Ph.D.

 

Engineering Recombinant Protein Vesicles for Delivery Applications

Recombinant proteins have emerged as promising building blocks for self-assembly of nanoparticles. Their versatility, accessibility through genetic manipulation, and biocompatibility are key advantages compared with synthetic block copolymers. One example of recombinant protein materials is hollow protein vesicles self-assembled from recombinant fusion proteins containing thermoresponsive elastin-like polypeptide (ELP). While synthetic nanoparticles typically require chemical conjugation or physical adsorption to incorporate biofunctional proteins, protein vesicles are made directly from biofunctional proteins. This prevents loss of protein structure and activity, and enables control over protein orientation. Vesicles use high-affinity leucine zippers, ZE and ZR, to enable a range of different biofunctional proteins to be displayed on the surface at a controlled density. The overall goal of this work is to translate protein vesicles into biofunctional materials made from bioactive proteins with the required physical and biological properties for use as delivery vehicles. For increased stability at physiological conditions, a photo-crosslinkable unnatural amino acid is incorporated into the ELP domain. Additionally, ELP hydrophobicity and length are engineered for desired size and stability. Vesicle size was reduced from micron-scale to nano-scale by tuning ionic strength, ELP hydrophobicity and length. To demonstrate the therapeutic potential of protein vesicles, a small molecule cancer treatment drug, doxorubicin, is encapsulated in the vesicle lumen and delivered into cancer cells. In addition to small molecule cargo in the lumen, a model antigen protein, ovalbumin, is fused ZE and incorporated into the surface of self-assembled vesicles with a controlled size and antigen density. The resulting antigen-displaying protein vesicles induce antigen-specific humoral and cellular immune responses in a mice model. This work is the first to make therapeutic protein vesicles and demonstrates the value of this platform in delivering a wide range of cargos with vastly different properties, ranging from small hydrophobic molecules to large, folded proteins.   

]]> Laura Paige 1 1655217961 2022-06-14 14:46:01 1655217961 2022-06-14 14:46:01 0 0 event BioE PhD Defense- "Engineering Recombinant Protein Vesicles for Delivery Applications" - Yirui Li

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<![CDATA[BioE PhD Defense- Paul Archer]]> 27917 Advisor:   

Susan Thomas, PhD  

  

Committee Members:  

Julie Champion, PhD  

Brandon Dixon, PhD  

Valeria Milam, PhD  

Krishnendu Roy, PhD  

 

Analysis of nanomaterial physiochemical property influences on lymph node accumulation and leukocyte association 

 

Lymph nodes house high concentrations of immune cells, and are critical tissues for regulating and priming the adaptive immune response. Thus, these tissues are an important therapeutic target for treatments that modulate immune activity, including but not limited to vaccination, induction of tolerance, and cancer immunotherapy. However, lymph nodes are also highly structured with physical and cellular barriers that can limit therapeutic access to important immune cell targets housed within them. Nanomaterial delivery approaches have been established to increase accumulation within the lymph node via locoregional methods of administration, but nanomaterials that highly efficiently accumulate within lymphatics are also restricted from entering the lymph node’s deeper regions in a size-dependent manner, limiting their delivery to lymphocytes. This motivates the need for better understanding and control over therapeutic access to cells within the lymph node, which is the overall objective of this thesis work. As such, work in the first part of this thesis quantifies the influences of lymphatic transport barriers on access of locoregionally administered nanomaterials to immune cell subsets within the tissue, and describes engineered biomaterial approaches to mitigate these barrier influences. Delivery to the lymph node from the blood supply via intravenous administration is next explored as a means to alter route of entrance to the lymph node and therefore distribution of cells accessed. Intravenous delivery is also standard practice for many cancer immunotherapies in the clinical setting, but delivery to the lymph node from this administration method is not well characterized, so nanomaterial properties favorable for intravenous delivery to immune cells within the lymph node are thoroughly studied. Finally, a cell-targeted antibody nanoparticle conjugate approach is employed to enhance delivery to T cells subsets specifically relevant in cancer immunotherapy. As a whole, this work provides new insights into therapeutic considerations for delivery to specific immune cell subsets within the lymph node and informs biomaterial design approaches to improve therapeutic outcomes.

]]> Laura Paige 1 1654176496 2022-06-02 13:28:16 1654176496 2022-06-02 13:28:16 0 0 event BioE PhD Defense- "Analysis of nanomaterial physiochemical property influences on lymph node accumulation and leukocyte association " - Paul Archer

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<![CDATA[BioE PhD Defense Presentation- Camila Camargo]]> 27917 Advisor:

Dr. Susan Thomas (Georgia Institute of Technology)

 

Committee Members:

Dr. Andrés García (Georgia Institute of Technology)

Dr. Krishnendu Roy (Georgia Institute of Technology)

Dr. Shuichi Takayama (Georgia Institute of Technology)

Dr. Edmund Waller (Emory University)

 

Adhesion analysis of CD8+ T cells using engineered microfluidic platforms to interrogate extravasation capacity for adoptive cell therapy

 

Adoptive cell therapy (ACT) has emerged as a powerful treatment option for patients with metastatic melanoma. Despite encouraging results with this treatment modality, responses are seen in only a minority of patients. It is now known that low patient rates of response are due to poor tumor-infiltrating lymphocytes (TIL) survival post-transfer as well as poor trafficking of transferred cells to relevant tissues. For TILs to infiltrate disease tissue from the blood vasculature, they utilize a highly orchestrated adhesion cascade that begins with selectin-mediated rolling adhesion to endothelial cells, chemokine-triggered integrin activation, followed by integrin-mediated firm adhesion and subsequent extravasation. These adhesion ligand-receptor interactions have been implicated in TIL homing, however, an outstanding problem in the field is a lack of understanding of how TIL’s surface adhesion ligands initiate and sustain adhesion interactions within the tumor vasculature, and how this may lead to improved engraftment of TILs to the tumor microenvironment. As such, the overall objective of this project is to utilize engineered microfluidic devices that enable the interrogation of adhesive behavior of cells under relevant hemodynamic forces to 1) analyze how cell adhesion is regulated by different microenvironments of the tumor vasculature, 2) determine what adhesion receptors, cytokines, and activation markers are present in highly adhesive cells and 3) determine if high adhesivity leads to increase tumor engraftment and therapeutic effects. Using in vitro microfluidic devices that mimic the hemodynamic environment of the tumor vasculature, we have elucidated the cellular characteristics of CD8+ T cells associated with selectin-mediated adhesion in flow. This work will provide insight into which subpopulation of CD8+ T cells is the most appropriate for enhanced tumor homing for ACT.

]]> Laura Paige 1 1654015002 2022-05-31 16:36:42 1654030269 2022-05-31 20:51:09 0 0 event BioE PhD Defense Presentation- "Adhesion analysis of CD8+ T cells using engineered microfluidic platforms to interrogate extravasation capacity for adoptive cell therapy" -Camila Camargo

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<![CDATA[BioE PhD Proposal Presentation- Lindsey Trejo]]> 27917 Advisor:  

Greg Sawicki, Ph.D. (Georgia Institute of Technology) 

Thesis Committee: 

Young-Hui Chang, Ph.D. (Georgia Institute of Technology) 

Young Jang, Ph.D. (Georgia Institute of Technology) 

Sabrina Lee, Ph.D. (Simon Fraser University) 

Rich Mahoney, Ph.D. (Intuitive) 

 

The interaction of passive and active ankle exoskeletons with age-related physiological changes to improve metabolic cost 

 

Difficulties with mobility were the most commonly reported disability for those age 65 and over. It is well known that older adults are slower and less economical during walking compared to young. This is thought to be brought on by reduced ankle push off power and a redistribution of positive power generation to more proximal joints (e.g., hip). Ankle exoskeletons have been shown to increase ankle push off, increase self-selected speed and reduce metabolic cost in young adults for a near immediate improvement in walking performance. There is a critical gap in understanding whether beneficial exoskeleton assistance strategies for younger adults will also benefit older adults and if so, what the underlying mechanism is that enables exoskeletons to reduce metabolic cost across age.  

Older adults have more compliant tendons than young, or a less stiff spring, operate with shorter less optimal muscle lengths, and exhibit reduced push-off power leading to a loss of the ‘spring in their step’. This necessitates higher muscle activations and reliance on muscles at less efficient joints like the hips, increasing metabolic cost during walking. Passive ankle exoskeletons have been shown in younger adults to lower the demand at the ankle, optimize complicated muscle-tendon dynamics during stance, and reduce metabolic cost. Muscle level changes in young adults in response to ankle exoskeletons to reduce metabolic cost led to wondering how ankle exoskeletons interact with age-related changes in physiology to reduce metabolic cost. The near-term objective of my work, is to evaluate the calf muscles and tendon’s role in modifying metabolic cost during walking with (i) passive, and (ii) active ankle exoskeletons across age. My central hypothesis is that ankle exoskeletons can offset age-related changes in physiology to reduce metabolic cost to that of young walking economy.  

 

I will use electromyography to measure muscle activity, B-mode ultrasound to track muscle level changes, and a portable indirect calorimetry system to measure metabolic cost in young and older adults with passive and active exoskeleton conditions. It is anticipated that these Aims will yield a greater understanding of how people interact with ankle exoskeletons to modify metabolic cost. These outcomes are expected to improve the design and control of ankle exoskeletons to improve the cost of walking across age, leading to greater mobility and increased quality of life. This will also clarify whether passive or active control is best for young or older adults. Passive devices are lighter weight, require less maintenance, and easier to conceal but they are less tunable and have shown lower reductions in metabolic cost. Active devices can be optimized for each person and provide more assistance at any timepoint in the gait cycle. However, motors and batteries make a lightweight device difficult to create and complicates usage with maintenance, battery life, bulkiness, and noise. This work will pave the way for studies in more functional measures such as increasing self-selected walking speed, improving balance, and reducing fatigue that may translate more directly to improved quality of life. 

]]> Laura Paige 1 1654014810 2022-05-31 16:33:30 1654014810 2022-05-31 16:33:30 0 0 event BioE PhD Proposal  Presentation- "The interaction of passive and active ankle exoskeletons with age-related physiological changes to improve metabolic cost " - Lindsey Trejo

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<![CDATA[BioE PhD Proposal- Michelle Quizon]]> 27917 Advisor:

Andrés J. García, Ph.D. (Georgia Institute of Technology)

Thesis Committee:

Edward A. Botchwey, Ph.D. (Georgia Institute of Technology & Emory University)

Rebecca D. Levit, M.D. (Emory University)

Edward A. Phelps, Ph.D. (University of Florida)

Krishnendu Roy, Ph.D. (Georgia Institute of Technology & Emory University)

 

 

Synthetic hydrogels for islet vascularization and engraftment in the subcutaneous space

 

                Type 1 diabetes (T1D) is a chronic, debilitating disease  characterized by the autoimmune destruction of insulin-producing b-cells located within pancreatic islets. The gold standard for T1D cell therapy is clinical islet transplantation (CIT), the infusion of islets through the hepatic portal vein. While CIT recipients demonstrate enhanced blood glucose control,  the procedure is limited to a marginal subset of T1D patients, in part due to the inhospitable nature of the intrahepatic site Indeed, an expected >60% loss of therapeutic cargo is expected within three days following transplantation. Thus, there is a significant need to establish an alternative extrahepatic transplant site that supports the engraftment of islets.

The subcutaneous space is an attractive extrahepatic transplant site for T1D cell therapy given its high clinical potential in terms of surgical accessibility, ease of monitoring, and convenience for replenishment and/or retrieval of therapeutic cargo. However, the unmodified subcutaneous space lacks adequate vascularization necessary to preserve functional islets. An elegant, facile strategy to promote neovascularization is the biomaterial-mediated delivery of proangiogenic factors such as vascular endothelial growth factor (VEGF). The objective of this project is to engineer injectable VEGF-delivering synthetic poly(ethylene glycol) [PEG] hydrogels that promote islet vascularization, engraftment, and function in the subcutaneous space. My central hypothesis is that the VEGF-delivering hydrogel can be tuned to do so. 

To test my hypothesis, I will first identify VEGF-PEG hydrogel formulations that support islet vascularization using an in vitro platform of vascularized islets. Next, I will evaluate lead VEGF-PEG hydrogel formulations in their ability to promote allogeneic islet vascularization, engraftment, and function in the subcutaneous spaces of diabetic rats and nondiabetic pigs. My work will result in an optimized injectable hydrogel for islet vascularization, engraftment, and function. Most significantly, it will provide a solid foundation for future work in a translational diabetic large animal model.

]]> Laura Paige 1 1652451174 2022-05-13 14:12:54 1652451174 2022-05-13 14:12:54 0 0 event BioE PhD Proposal- "Synthetic hydrogels for islet vascularization and engraftment in the subcutaneous space"-  Michelle Quizon

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<![CDATA[BioE PhD Defense- Maggie Manspeaker]]> 27917 Advisor: Susan Thomas, PhD (Georgia Institute of Technology)

Committee:

John Blazeck, PhD (Georgia Institute of Technology)

Julie Champion, PhD (Georgia Institute of Technology)

M.G. Finn, PhD (Georgia Institute of Technology)

Haydn Kissick, PhD (Emory University School of Medicine)

 

Engineered Nanotechnology for the Delivery of Cancer Immunotherapies to Lymph Nodes to Modulate Anti-Tumor T Cell Immunity

 

The advent of immunotherapies, particularly immune checkpoint blockade (ICB) monoclonal antibodies (mAbs), to treat advanced cancers has drastically improved outcomes for some patients. These ICB mAbs work by blocking inhibitory immune checkpoint pathways and more recently have been shown to cause a proliferative burst of effector T cells attributable to a subset of antigen-specific CD8 T cells with stem cell-like properties, which are thought to reside in lymphoid tissues and in particular tumor–draining lymph nodes (TdLNs). TdLNs are a critically important tissue that mediates the mounting of effective anti-tumor immunity and are central in the response to ICB immunotherapy both due to active immune checkpoints in TdLNs and their role in housing CD8 stem-like cells. However, despite the promising clinical advances ICB mAbs represent, some patients experience no clinical benefit from therapy, leading to an increase in clinical investigations into various combination therapies that enhance patient response, such as adjuvants and chemotherapies. Additionally, success of cancer therapeutics is often stymied by low accumulation in target tissues and off-target effects. Therefore, a better understanding of how these combination therapies interact with the TdLN and resulting immune response is needed, which can be enabled with the use of nanotechnologies that improve therapeutic efficacy while avoiding success-limiting off-target effects. As such, the overall objective of this project is to use nanotechnologies that enable drug accumulation in the TdLN to 1) investigate how nanotechnology alters the efficacy of combination chemo- and immunotherapy and characterize the involvement of the TdLN in anti-tumor immunity following treatment, and to 2) elucidate the dynamics of CD8 stem-like T cells in response to adjuvant and ICB combination therapy, and characterize the efficacy of engineered drug delivery nanotechnologies on these combinations. This work will provide insight into role of the TdLN, and dynamics of important cell populations within, in the efficacy of drug and ICB combination therapies with clinical relevance and inform promising future therapeutic strategies for cancer.

]]> Laura Paige 1 1652451032 2022-05-13 14:10:32 1652451032 2022-05-13 14:10:32 0 0 event BioE PhD Defense- "Engineered Nanotechnology for the Delivery of Cancer Immunotherapies to Lymph Nodes to Modulate Anti-Tumor T Cell Immunity" -Maggie Manspeaker

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<![CDATA[BioE PhD Proposal- Elio Challita]]> 27917 Advisor: Saad Bhamla, Ph.D. (Georgia Institute of Technology)

Committee:

David Hu, Ph.D. (Georgia Institute of Technology)

Sunghwan ‘Sunny’ Jung, Ph.D. (Cornell University)

Sheila Patek, Ph.D. (Duke University)

Simon Sponberg, Ph.D. (Georgia Institute of Technology)

 

Fast, furious, and frugal: Principles of drops, jets, and damping in extreme invertebrates

and design of low-cost scientific tools

 

Sharpshooter insects (Hemiptera: Cicadellidae) are pierce-sucking insects that feed on plant’s xylem fluid. Due to the poor nutritious content of the xylem sap, sharpshooter insects extract almost 300 times their body weight worth in plant fluids. To prevent fluidic buildup, these insects discharge their liquid excreta in the form of discrete water droplets before flinging them away using a resilin-based biological spring found in their anal stylus. In this thesis, we consider this distinctive droplet-catapulting phenomenon observed in sharpshooter insects during excretion. Through an experimental, mathematical and computational approach, we explore the physical limits of such a unique droplet propulsion strategy and show why it is energetically favorable for these insects to fling their droplet excreta instead of using other mechanisms such as ‘jetting’ and ‘dripping’. Using dimensionless analysis, we show how biological organisms living in a world governed by surface tension develop exquisite strategies to overcome capillary adhesion during fluidic ejection. 

In parallel, we present a mathematical framework for the arrest and damping of ultra-fast movements in biological organisms. We consider the behavior of two organisms: the rapid launch of slingshot spiders (Araneae: Theridiosomatidae) and the controlled landing springtails (Arthropoda: Collembola) at the water-air surface. 

Finally, we define the principles of curiosity-driven frugal science. We discuss two open-hardware devices: Trackoscope, a low-cost microscope for autonomously tracking micro-organisms; and Opencell, a low-cost platform for synthetic biology that reproduces the functionality of three ubiquitous devices - a cell disruptor, microcentrifuge, and vortex mixer.

]]> Laura Paige 1 1651593095 2022-05-03 15:51:35 1651593135 2022-05-03 15:52:15 0 0 event BioE PhD Proposal-  "Fast, furious, and frugal: Principles of drops, jets, and damping in extreme invertebrates and design of low-cost scientific tools" - Elio Challita

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<![CDATA[BioE PhD Proposal- Bryan Wang]]> 27917 Krishnendu Roy, Ph.D. (Advisor), Department of Biomedical Engineering, Georgia Institute of Technology & Emory University

Carolyn Yeago, Ph.D. (Co-Advisor), Marcus Center for Therapeutic Cell Characterization and Manufacturing

Johnna Temenoff, Ph.D., Department of Biomedical Engineering, Georgia Institute of Technology & Emory University

Fani Boukuvala, Ph.D. School of Chemical & Biomolecular Engineering, Georgia Institute of Technology

Stephen Balakirsky, Ph.D., Georgia Tech Research Institute

 

Process Development and Process Analytical Technology Integration for Cell Therapy Manufacturing

Cell therapies have the potential to effectively treat and even cure complex, currently untreatable diseases with unprecedented success. Despite the tremendous promise, significant and unique challenges must be overcome to make cell therapy manufacturing reproducible, scalable, high-quality, and cost-effective. The many challenges of cell therapy manufacturing are primarily because the therapy itself is composed of live cells. Cells are highly responsive to their surrounding conditions and endure rigorous processing from procurement to administration into a patient. The upstream cell expansion process is critical for producing high-yield and high-quality cell products. This step utilizes bioreactors as a unit operation to cultivate desired cell types. Current bioreactors for cell therapies are unresponsive, manual, and poorly characterized for each specific product. Process analytical technology (PAT) is a system to characterize, monitor, and eventually control the process to ensure final product quality. PAT is a powerful tool that has been successfully implemented in the pharmaceutical industry but remains mostly unexplored in the cell therapy industry. This thesis project aims to (1) design bench-scale bioreactors and processes configurable to PAT integration; (2) utilize PAT and biological assays to characterize expansion processes and products to determine critical process parameters; (3) compare different bioreactor types and use PAT to understand how process parameters contribute to product differences. The overall approach will be applied to two different cell types: Mesenchymal Stromal Cells and T Cells, each requiring a unique culture environment. The overall objective of this thesis is to leverage engineering tools to better understand the biology behind the cell expansion processes in bioreactors. The central hypothesis is that bioreactors can effectively expand therapeutic cells, and PAT integration on bioreactors can enhance process understanding and mitigate risks associated with at-scale cell therapy manufacturing. 

]]> Laura Paige 1 1651066919 2022-04-27 13:41:59 1651066919 2022-04-27 13:41:59 0 0 event BioE PhD Proposal- "Process Development and Process Analytical Technology Integration for Cell Therapy Manufacturing" - Bryan Wang

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<![CDATA[9th Annual BioE Day]]> 27195 Celebrating the 30th anniversary of IBB's interdisciplinary Bioengineering program.

Presentations from 2022 BioE Award Winners, featured BioE Alum Seminar, Rapid Fire Thesis Competition, and Outstanding Abstract Presentations. Lunch to be served.

BioE Day Website

Open to all Bioengineering Students and Faculty!
 

]]> Colly Mitchell 1 1650641722 2022-04-22 15:35:22 1650642807 2022-04-22 15:53:27 0 0 event 2022-05-13T13:00:00-04:00 2022-05-13T18:00:00-04:00 2022-05-13T18:00:00-04:00 2022-05-13 17:00:00 2022-05-13 22:00:00 2022-05-13 22:00:00 2022-05-13T13:00:00-04:00 2022-05-13T18:00:00-04:00 America/New_York America/New_York datetime 2022-05-13 01:00:00 2022-05-13 06:00:00 America/New_York America/New_York datetime <![CDATA[]]> Mercedes Gonzalez
Hanhao Spencer Zhang

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<![CDATA[BioE PhD Defense Presentation- Troy Batugal]]> 27917 Advisor: Ravi S. Kane, Ph.D. (Georgia Institute of Technology) 

 

Committee: 

Andrés García, Ph.D. (Georgia Institute of Technology) 

Blair Brettmann, Ph.D. (Georgia Institute of Technology) 

Corey Wilson, Ph.D. (Georgia Institute of Technology) 

Julie Champion, Ph.D. (Georgia Institute of Technology) 

 

DESIGN AND CHARACTERIZATION OF MODIFIED LYTIC ENZYMES AND NANOPARTICLE-BASED VACCINES TO COMBAT S. AUREUS 

 

There is an imminent threat posed by the expanding list of “superbugs” or antibiotic-resistant bacteria that cause life-threatening infections. Methicillin-Resistant Staphylococcus aureus (MRSA) is one such superbug that is easily spread in hospitals and within communities. Many therapeutics fail to adequately treat infections caused by MRSA, leaving clinicians and patients with few options such as last resort antibiotics. The rapid pace of evolution of antimicrobial resistance to new and last resort antibiotics necessitates research and development of viable alternative strategies for preventing and treating infections. Our approach for tackling this growing public health concern involves three aims: incorporation of reactive handles into lytic enzymes, modification of lytic enzymes to reduce their immunogenicity, and designing vaccines that elicit broadly protective antibodies against S. aureus

First, lytic enzymes such as lysostaphin are modular antimicrobials that could have activity against antibiotic-resistant bacteria. Engineering these enzymes with reactive moieties can greatly broaden their potential applications to include incorporation in wound-healing biomaterials. 

Second, the efficacy of lytic enzymes in vivo is stymied by their low half-life and the potential to elicit an immune response. We offer two different approaches for reducing the immunogenicity of lytic enzymes: using site-specific pegylation or using site-specific glycosylation. 

Third, S. aureus has an arsenal of toxins and mechanisms that facilitate evasion of the host immune system. A vaccine that can elicit broad protection against multiple S. aureus toxins is needed to reduce infections and disease severity. We aim to design and characterize a protein-based vaccine against S. aureus that can elicit antibodies that can neutralize multiple members of a family of S. aureus toxins. 

 

]]> Laura Paige 1 1650291699 2022-04-18 14:21:39 1650291699 2022-04-18 14:21:39 0 0 event BioE PhD Defense Presentation-  "DESIGN AND CHARACTERIZATION OF MODIFIED LYTIC ENZYMES AND NANOPARTICLE-BASED VACCINES TO COMBAT S. AUREUS " - Troy Batugal

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<![CDATA[BioE PhD Proposal Presentation- Elijah Holland]]> 27917 Advisor: Andrés García, Ph.D. (Georgia Institute of Technology)

 

Committee:

Cheng Zhu, Ph.D. (Georgia Institute of Technology)

Wilbur Lam, Ph.D.(Georgia Institute of Technology)

John Blazeck, Ph.D.(Georgia Institute of Technology)

Jiangping Fu, Ph.D. (University of Michigan)

Title

Mechanotransduction at Focal Adhesions: Interplay among Force, FAK, and YAP 

 

Abstract

Dynamic cell-cell and cell-ECM (extracellular matrix) interactions regulate tissue morphogenesis and wound healing through modulating cellular processes such as differentiation and cell migration. Adhesive interactions function as the primary way cells turn upstream ECM cues into downstream cellular processes. Focal adhesions (FA), clusters of structural and signaling proteins, function as principal sites of force transfer and mechanotransduction. Previous studies in mechanobiology demonstrated that FAs are mechanosensitive, but the mechanism for how FAs are involved in mechanotransduction remains poorly defined. Recent studies have implicated FAs with yes associated protein (YAP), a transcriptional coactivator that can turn mechanical cues like substrate rigidity into changes in gene expression. These studies have shown that the inhibition of certain FA proteins has led to a reduction in YAP nuclear localization, and it was demonstrated that YAP also promotes the transcription of FA-related genes. This link needs to be explored; however, this can only be accomplished with an experimental platform with high spatiotemporal resolution. The objective of this project is to elucidate the mechanism by which cells take information at the cell periphery and communicate it to the nucleus. This proposal hypothesizes that FAs function as mechanosensors through focal adhesion kinase (FAK), where FAK impacts YAP nuclear localization by either modulating nuclear lamin phosphorylation or expression, therefore, altering nuclear stiffness or by modulating PLCγ1 activity, therefore, altering levels of phosphatidylinositol 4,5-bisphosphate (PIP2) which alters RAP2 activity, and that FAs utilize their quantity and spatial distribution across the cell to direct YAP nuclear localization. This hypothesis will be tested via three specific aims: (1) characterize the effect of FAK-talin-vinculin functionalities and interactions on YAP nuclear localization and YAP related transcriptional activity; (2) characterize the effects of FA number, area, and spatial distribution across the cell body on YAP nuclear localization and YAP related transcriptional activity; and (3) investigate whether FAK modulates YAP localization by regulating PLCγ1 activity leading to changes in RAP2 activity and YAP nuclear localization or by altering lamin expression or phosphorylation leading to changes in nuclear stiffness and nuclear pore organization which alters YAP nuclear localization. With these studies, an experimental platform with high spatiotemporal resolution will be generated; the molecular mechanism by which FAs and FAK impact YAP signaling will be explored; and new insights will be generated in mechanobiology.

]]> Laura Paige 1 1649774141 2022-04-12 14:35:41 1649774141 2022-04-12 14:35:41 0 0 event BioE PhD Proposal Presentation- "Mechanotransduction at Focal Adhesions: Interplay among Force, FAK, and YAP " - Elijah Holland

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<![CDATA[BioE MS Thesis Defense- Anna Harrison]]> 27917 Committee:
Omer T. Inan, Ph.D. (Advisor) (School of Electrical and Computer Engineering, Georgia Institute of Technology)
J. Douglas Bremner, M.D.  (Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine)
Robert J. Butera, Ph.D.  (Department of Biomedical Engineering, Georgia Institute of Technology and Emory University)

 


TRANSCUTANEOUS CERVICAL VAGUS NERVE STIMULATION FOR OPIOID USE DISORDER

 

In the United States, opioid use disorder is quickly becoming a leading cause of death and a public health emergency.  Opioid dependence is incredibly debilitating and pervasive; even if patients would like to end opioid use, the extreme withdrawal symptoms often discourage patients.  Medication assisted treatment of opioid use disorder is the current gold standard for patient care, but patients must undergo a ‘washout’ period wherein they are unable to use opioids or begin medication assisted treatment and are particularly susceptible to withdrawal symptoms and accidental overdose.  Transcutaneous cervical vagus nerve stimulation (tcVNS) is a treatment modality that has been proposed for opioid use disorder patients during this period of early abstinence, as this treatment effects the same brain regions that are responsible for withdrawal and craving symptoms.  Additionally, tcVNS offers a device-based (rather than medication-based), noninvasive, low-risk, inexpensive option for treatment of opioid use disorder.

This thesis outlines a double-blind, sham-controlled, randomized clinical study to determine the effectiveness of tcVNS for patients undergoing acute opioid withdrawal.  Several sensors were used to record biosignals and extract biomarkers of autonomic nervous system functionality; additionally, subjective surveys were used to determine patient perception of their withdrawal and craving symptoms.  Methodologies of biomarker extraction are explored, and the effectiveness of tcVNS for reducing opioid withdrawal symptoms is assessed.  Though more investigation is required, preliminary data suggests that tcVNS is effective in reducing withdrawal symptoms, pain, and distress; additionally, several biomarkers showed significant differences between active and sham groups, suggesting that autonomic nervous system activity is altered during tcVNS in patients undergoing active opioid withdrawal.

]]> Laura Paige 1 1649355248 2022-04-07 18:14:08 1649355248 2022-04-07 18:14:08 0 0 event BioE MS Thesis Defense-  " TRANSCUTANEOUS CERVICAL VAGUS NERVE STIMULATION FOR OPIOID USE DISORDER" - Anna Harrison

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<![CDATA[BioE PhD Proposal- Mighten Yip]]> 27917 Advisor:

Craig Forest, PhD (Georgia Institute of Technology)

Committee:

Ming-fai Fong, PhD (Georgia Institute of Technology)

Chengzhi Shi, PhD (Georgia Institute of Technology)

Christopher Valenta, PhD (Georgia Tech Research Institute)

Matt Rowan, PhD (Emory University)

Stephen Traynelis, PhD (Emory University)

 

Towards automation of multimodal cellular electrophysiology

Understanding how the neurons of the brain communicate, connect, and respond to stimuli is a fundamental goal of neuroscience. Whole-cell patch clamp recording in vitro represents the gold standard method for measuring electrophysiology, morphology, and connectivity properties of single neurons—an ideal method for classifying neuronal cell types. Furthermore, the high spatiotemporal resolution provided by whole-cell patch clamping is particularly helpful in engineering better pharmacological, optogenetic, and chemigenetic effectors which can help lead to better tools to treat neural diseases and study the brain. However, the manual, laborious, and time-consuming nature of patch clamping experiments have limited the throughput and number of cells that can be sampled per day. To improve the throughput for these single cell, high spatiotemporal experiments, this work will focus on developing automated, robotic methods for cell-specific patch clamping to enable rapid characterization of cells to study their electrophysiological response to effectors and local synaptic connectivity. Towards this goal, I propose to (1) integrate automated patch clamping with discovery experiments for cellular indicators and effectors, (2) develop a machine learning algorithm for real-time neuron detection of neurons in brain slices for in vitro patch clamping, and (3) create a coordinated multi-pipette patch clamp algorithm for enabling high throughput synaptic connectivity studies. The development of these technologies will create a system that allows for high-efficiency experiments that yield multimodal cellular electrophysiology.

]]> Laura Paige 1 1649171506 2022-04-05 15:11:46 1649171716 2022-04-05 15:15:16 0 0 event BioE PhD Proposal- "Towards automation of multimodal cellular electrophysiology" -Mighten Yip

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<![CDATA[BioE PhD Defense - Seleipiri Charles]]> 27917 Advisor: 

Hang Lu, Ph.D. (Georgia Institute of Technology) 

Committee: 

Melissa Kemp, Ph.D. (Georgia Institute of Technology) 

Zhexing Wen, Ph.D. (Emory School of Medicine) 

Johnna Temenoff, Ph.D. (Georgia Institute of Technology) 

Wilbur Lam, Ph.D. (Georgia Institute of Technology) 

  

Microfluidic tools for studying development in embryos and brain organoids 

 

Development in multicellular organisms is a complex process requiring multiple intracellular and extracellular signaling events. High content screening tools enable the cellular and subcellular assessment of developmental changes, which in turn have led to a variety of genetic, pharmacological, and therapeutic advancements involving multicellular organisms. Developing high-content screening tools for multicellular systems requires high-resolution imaging of protein and gene expression changes, a relatively large number of samples to better characterize inter and intra-population differences, and multiplexed readouts using the same sample to obtain layered information about developmental changes. Microfluidics can address these challenges by enabling high magnification imaging, parallelization, rapid reagent delivery and exchange, and lower reagent consumption. Hence, this thesis seeks to address high content screening challenges that affect the study of development in active areas of research in my lab using microfluidics:  C. elegans embryogenesis and cellular development of brain organoids. This thesis will demonstrate this through three specific aims that involve developing and improving microfluidic-based technology and assays for large-scale imaging and characterization. As a result, I will develop a microfluidic-based assay for conducting high temporal resolution measurements of gene expression changes during C. elegans embryogenesis using single-molecule fluorescence in situ hybridization (aim 1). Next, I developed an integrated platform to enable robust and long-term culturing of brain organoids. I designed a mesofluidic bioreactor device based on a unique diffusion-reaction scaling theory, which achieves convective media exchange for sufficient nutrient delivery in long-term culture (aim 2). Finally, I modified aspects of the integrated platform developed in aim 2 to enable live and longitudinal imaging of organoids during culture for in situ characterization of cell quality and differentiation (aim 3). Combining high throughput microfluidic technology with high content imaging tools will improve the characterization of factors affecting development in these two biological systems. 

]]> Laura Paige 1 1649171677 2022-04-05 15:14:37 1649171677 2022-04-05 15:14:37 0 0 event  BioE PhD Defense -  "Microfluidic tools for studying development in embryos and brain organoids " -Seleipiri Charles

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<![CDATA[BioE MS Thesis Presentation- Emily Upton]]> 27917 Aaron Young, Ph.D. (Advisor) (School of Mechanical Engineering, Georgia Institute of Technology)
Gregory Sawicki, Ph.D. (School of Mechanical Engineering, Georgia Institute of Technology)
Trisha Kesar, Ph.D.  (Department of Rehabilitation Medicine, Emory University School of Medicine)

  

Exoskeleton Assistance with Vibrotactile and Auditory Biofeedback for Post-Stroke Gait Retraining  

Stroke is the leading cause of disability in America with 80% of post-stroke individuals left with gait impairments. Rehabilitation post-stroke is very important to encourage, retrain, and assist proper gait mechanics. Usually, post-stroke gait is highly asymmetric between the affected and non-affected limbs. Due to hemiplegia on the affected limb, a smaller ankle moment causes reduced propulsion and slower walking speed. Using various rehabilitation strategies (including exoskeletons and biofeedback), these deficits can be reduced, and gait can be improved. It is unknown how the combination of biofeedback and exoskeleton assistance changes the kinematic, kinetic, and spatiotemporal outcomes of post-stroke individuals. In this thesis, a biofeedback system was created to measure the trailing limb angle in real-time and provide vibrotactile and auditory biofeedback to the user. By targeting the trailing limb angle, propulsion and walking speed can be improved. Experiments were performed to analyze the effects of an ankle exoskeleton and hip exoskeleton with and without biofeedback on post-stroke individuals. This was done to determine whether the combination of exoskeleton assistance and biofeedback improves propulsion and walking speed more than the paradigms alone and when compared to baseline. This thesis covers the design of the biofeedback system, the experimental procedures performed, and analysis of the results of each experiment.  

]]> Laura Paige 1 1648644802 2022-03-30 12:53:22 1648644802 2022-03-30 12:53:22 0 0 event BioE MS Thesis Presentation- "Exoskeleton Assistance with Vibrotactile and Auditory Biofeedback for Post-Stroke Gait Retraining"  Emily Upton

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404-852-5232

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<![CDATA[BioE PhD Defense Presentation- Gilad Doron]]> 27917 Advisors

Johnna Temenoff, PhD (Georgia Institute of Technology)

Robert Guldberg, PhD (University of Oregon)

 

Committee

Nick Willett, PhD (University of Oregon)

Levi Wood, PhD (Georgia Institute of Technology)

Christopher Evans, PhD (Mayo Clinic)

 

Title: Culture Systems for controlling mesenchymal stromal cell, protein, and cell-secreted protein release

 

Abstract: Mesenchymal stromal cells (MSCs) are highly-secretory cells that are of great clinical interest, due to their immunomodulatory and pro-regenerative properties when transplanted in vivo. Despite their clinical potential, current methods commonly used for MSC culture are unsuitable for their production as secretory cell therapies at clinical- or commercial scales. Furthermore, their development has been limited by a poor understanding of mechanisms regulating MSC secretory and therapeutic function. Comprehensive investigation of different conditioning strategies and culture systems is needed to identify those critical to improving the production of MSCs and MSC-secreted factors. Doing so may also reveal key cellular processes controlling therapeutic factor release, which may be further leveraged to improve MSC potency.

The long-term goal of this thesis was to develop culture systems for better understanding and controlling the release of cells, proteins, and cell-secreted proteins towards improved MSC scaling and, ultimately, potency as a therapeutic product. First, multiomics characterization of MSCs cultured in monolayer and as aggregates was performed to evaluate changes to cell physiology corresponding with enhanced secretory activity. Additionally, MSCs were cultured on hydrogel substrates with different mechanical and biochemical properties to determine those most important for controlling MSC proliferation and secretion. Next, one critical culture substrate property (stiffness) was utilized to develop microcarriers for improving secretion by genetically-modified MSCs. Lastly, a novel culture substrate responsive to Factor Xa was developed for on-demand release of MSCs from culture, as well as for the release of proteins for therapeutic applications. Overall, this work provides strategies for better interrogating and improving MSC bioactive factor release, which may be used to further develop highly efficacious MSC-based therapies, as well as other therapies that rely on responsive release of bioactive agents.

]]> Laura Paige 1 1648644213 2022-03-30 12:43:33 1648644213 2022-03-30 12:43:33 0 0 event BioE PhD Defense Presentation- "Culture Systems for controlling mesenchymal stromal cell, protein, and cell-secreted protein release"  Gilad Doron

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<![CDATA[BioE MS Thesis Presentation- Vidisha Goyal]]> 27917 Ross C. Ethier, Ph.D. (Advisor) (Department of Biomedical Engineering, Georgia Institute of Technology and Emory University)
Brandon Dixon, Ph.D. (School of Mechanical Engineering, Georgia Institute of Technology)
Pamela T. Bhatti, Ph.D.  (School of Electrical and Computer Engineering, Georgia Institute of Technology)

 

Deep Learning-based Optic Nerve Analysis 

Axon loss and degeneration are used to quantify the progression of several neurodegenerative diseases such as glaucoma, multiple sclerosis, etc. in animal models. In glaucoma, the gold standard for quantifying nerve health post-mortem is manual counting of axons from light micrographs of the optic nerve, which is subjective and laborious. This research is focused on developing a deep-learning model to segment normal-appearing axons, their axoplasm, and myelin sheath, from whole optic nerve images. These segmentation maps are fed into an image-processing pipeline for post-processing and for computing morphometric properties such as axoplasmic area, eccentricity, diameter, etc. With this technology, we will be able to answer important questions such as “Which axon size is preferentially damaged during glaucoma?” and “How does axon morphology change with increase optic nerve damage?” etc. Therefore, a reference RGC axonal atlas for Brown Norway rats was also constructed. A reference atlas of optic nerve RGC axonal morphological metrics could facilitate studies of neuro-ophthalmic diseases, such as glaucoma, by allowing sensitive detection of subtle RGC axonal changes and help answer some of the questions posed above.  

]]> Laura Paige 1 1647351025 2022-03-15 13:30:25 1647351025 2022-03-15 13:30:25 0 0 event BioE MS Thesis Presentation-  "Deep Learning-based Optic Nerve Analysis " Vidisha Goyal

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2022-04-15T11:00:00-04:00 2022-04-15T13:00:00-04:00 2022-04-15T13:00:00-04:00 2022-04-15 15:00:00 2022-04-15 17:00:00 2022-04-15 17:00:00 2022-04-15T11:00:00-04:00 2022-04-15T13:00:00-04:00 America/New_York America/New_York datetime 2022-04-15 11:00:00 2022-04-15 01:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Proposal Presentation- Saeyoung Kim]]> 27917 Advisor: Brooks D. Lindsey (Georgia Institute of Technology and Emory University)

 

Committee:

Stanislav Emelianov (Georgia Institute of Technology and Emory University)

Alessandro Veneziani (Emory University)

John Oshinski (Georgia Institute of Technology and Emory University)

Costas D. Arvanitis (Georgia Institute of Technology Georgia Tech)

 

 

Development of a forward-viewing high frequency ultrasound for velocity and wall shear stress estimation in coronary arteries

 

Coronary artery disease is the most common type of cardiovascular disease, affecting > 18 million adults, and is responsible for > 365 k deaths per year in the U.S. alone. Wall shear stress (WSS) is an indicator of likelihood of plaque rupture in the coronary artery disease, however, non-invasive estimation of 3D blood flow velocity and WSS is challenging due to the requirement for high spatial resolution at deep penetration depths. For this reason, catheter-based forward-viewing intravascular ultrasound (FV IVUS) imaging system is being developed to estimate real-time 3D velocity fields. This study aims to develop a velocity and WSS estimation technique for a forward-viewing high frequency ultrasound array transducer in a coronary artery with an intermediate stenosis. The Aims of this project are: 1) Ultrasound-based blood flow velocity and WSS estimation approaches will be compared in a patient-specific coronary artery geometry, 2) motion correction techniques will be developed and implemented to accurately estimate WSS even in the presence of dynamic cardiac motion, and 3) the developed techniques will be evaluated in an in vivo coronary environment. This work will determine the accuracy of ultrasound-based blood flow velocity and WSS estimation techniques using a forward-viewing, high frequency ultrasound transducer for characterizing the coronary environment and assessing plaque vulnerability.

]]> Laura Paige 1 1646837826 2022-03-09 14:57:06 1646837826 2022-03-09 14:57:06 0 0 event BioE PhD Proposal Presentation- "Development of a forward-viewing high frequency ultrasound for velocity and wall shear stress estimation in coronary arteries"- Saeyoung Kim

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2022-03-21T10:00:00-04:00 2022-03-21T12:00:00-04:00 2022-03-21T12:00:00-04:00 2022-03-21 14:00:00 2022-03-21 16:00:00 2022-03-21 16:00:00 2022-03-21T10:00:00-04:00 2022-03-21T12:00:00-04:00 America/New_York America/New_York datetime 2022-03-21 10:00:00 2022-03-21 12:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Proposal- Jacob Davis]]> 27917 Committee:
Eberhard Voit, Ph.D. (Advisor) (Department of Biomedical Engineering, Georgia Institute of Technology and Emory University)
Sam Brown, Ph.D. (Advisor)  (School of Biological Sciences, Georgia Institute of Technology)
Melissa Kemp, Ph.D  (Department of Biomedical Engineering, Georgia Institute of Technology and Emory University)
Arlene Stecenko, M.D. (Department of Pediatrics, Emory University School of Medicine)
Mark Styczynski, Ph.D (School of Chemical and Biomolecular Engineering, Georgia Institute of Technology)
Denis Tsygankov, Ph.D (Department of Biomedical Engineering, Georgia Institute of Technology)

Experimental and Computational Analysis of Pathogen Emergence and Antibiotic Resistance in a Cystic Fibrosis Airway Infection Model

The human body harbors at least twice as many bacteria cells as human cells. Most of these bacteria are harmless, but the emergence of pathogens is common in many human body systems. Treatment of these infections are often with antibiotics can have non-target effects and remove protective flora from the body. This dissertation project was designed to create a model system of airway bacterial communities that is amenable to the development of effective experimental and computational investigations that shed light on pathogen emergence and antibiotic resistance. For the experimental analysis, I will transform three common bacterial species in human airways with the goal of making them easily quantifiable with available microscopic and spectrophotometric techniques. The bacteria will be grown in a minimal medium and their dynamics will be studied. To quantify the interactions among the different species and predict the dynamics of the community under different settings, mathematical models within the Lotka-Volterra framework will be developed and parameterized. Validation will be performed with a synthetic sputum medium in a porcine lung model. Select metabolites in the model community will be tracked over time, using mass spectrometry and enzymatic assays. Community resistance to a common beta-lactam antibiotic will be studied by tracking how the antibiotic is hydrolyzed by beta-lactamase enzymes of non-targeted species. The existing modeling framework will be expanded to incorporate this antibiotic and metabolic data in the community model. Although the community size of the model system will be small - to allow for comprehensive data generation - this experimental and mathematical system will constitute a prototype for investigating larger models that can be used to predict how pathogens survive in different communities and under altered environmental conditions and antibiotic treatments.

]]> Laura Paige 1 1638477836 2021-12-02 20:43:56 1638477836 2021-12-02 20:43:56 0 0 event BioE PhD Proposal- "Experimental and Computational Analysis of Pathogen Emergence and Antibiotic Resistance in a Cystic Fibrosis Airway Infection Model" - Jacob Davis

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2021-12-20T10:00:00-05:00 2021-12-20T12:00:00-05:00 2021-12-20T12:00:00-05:00 2021-12-20 15:00:00 2021-12-20 17:00:00 2021-12-20 17:00:00 2021-12-20T10:00:00-05:00 2021-12-20T12:00:00-05:00 America/New_York America/New_York datetime 2021-12-20 10:00:00 2021-12-20 12:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Proposal- Phillip Tran]]> 27917 Advisor: 

Prof. Jaydev P. Desai (School of Biomedical Engineering, Georgia Institute of Technology)

 

Committee:

Prof. Omer Inan (School of Electrical and Computer Engineering, Georgia Institute of Technology)

Prof. Boris Prilutsky (School of Biological Sciences, Georgia Institute of Technology)

Prof. Greg Sawicki (School of Mechanical Engineering, Georgia Institute of Technology)

Prof. Aaron Young (School of Mechanical Engineering, Georgia Institute of Technology)

 

Title: Development of a tendon-driven, voice-controlled soft robotic hand exoskeleton

Functional hand movement is an important component of many activities of daily living, such as using a phone or eating. Cervical spinal cord injury (SCI) can severely impact hand motor and sensory function, and accordingly, patients with SCI are often unable to complete basic everyday tasks without assistance. The focus of this proposed work is to develop and evaluate a robotic system to improve hand and finger functionality during the performance of everyday tasks in individuals with hand dysfunction. First, a tendon-driven, voice-controlled soft robotic assistive hand exoskeleton is designed and developed with the purpose of providing active assistance to users during grasping and pinching motions. Second, a self-sealing suction cup is developed and integrated into an exoskeleton system to explore alternate strategies for the manipulation of objects. Finally, the developed exoskeleton system is evaluated on individuals with and without hand dysfunction to characterize the performance of the system in clinically relevant settings. Successful completion of the proposed work will result in a step towards a clinically relevant assistive robotic system for individuals with hand dysfunction.

 

]]> Laura Paige 1 1638477645 2021-12-02 20:40:45 1638477645 2021-12-02 20:40:45 0 0 event BioE PhD Proposal- "Development of a tendon-driven, voice-controlled soft robotic hand exoskeleton" - Phillip Tran

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2021-12-14T10:00:00-05:00 2021-12-14T12:00:00-05:00 2021-12-14T12:00:00-05:00 2021-12-14 15:00:00 2021-12-14 17:00:00 2021-12-14 17:00:00 2021-12-14T10:00:00-05:00 2021-12-14T12:00:00-05:00 America/New_York America/New_York datetime 2021-12-14 10:00:00 2021-12-14 12:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Proposal- Adriana Mulero- Russe]]> 27917 Advisor:
Andrés García, Ph.D., School of Mechanical Engineering, Georgia Institute of Technology

 

Committee Members:

Michael A. Helmrath, M.D., Division of Pediatric General and Thoracic Surgery, Cincinnati Children’s Hospital Medical Center

Hang Lu, Ph.D. School of Chemical & Biomolecular Engineering, Georgia Institute of Technology

Asma Nusrat, M.D., Department of Pathology University of Michigan

Johnna S. Temenoff, Ph.D., School of Biomedical Engineering Georgia Institute of Technology

 

Engineered Synthetic Platform for Human Intestinal Organoid Generation and Delivery 

 

Human intestinal organoids (HIOs) are three-dimensional (3D) multicellular structures, derived from either adult intestinal stem cells or human pluripotent stem cells (hPSCs), that recapitulate human intestinal tissue architecture. HIOs are a promising cell source for intestinal tissue repair, disease modeling, and drug screening. Previous work has demonstrated that HIOs engraft to the injured intestinal wall in vivo, however, these approaches are significantly limited by the lack of an appropriate delivery vehicle to drive HIO engraftment. HIO generation from hPSCs is a multi-stage directed differentiation process comprising three stages: (I) a definitive endoderm 2D monolayer, (II) self-organized 3D aggregates (human intestinal spheroids, HIS), and (III) intestinal specification into HIOs within a 3D extracellular matrix. This in vitro culture process spans a 2D growth substrate (stage I and II) to a 3D matrix (stage III). The growth stages (2D and 3D) are supported by Matrigel, a murine tumor-derived basement membrane extract with ill-defined composition, lot-to-lot variability, and limited clinical translation potential presenting a major roadblock to HIOs clinical translation. Another roadblock to HIO technologies is the low yield and consistency of HIS differentiation in HIOs. The objectives of this project are to (1) engineer a synthetic hydrogel platform with independent control of the biochemical and biophysical cues guiding the entire in vitro differentiation of hPSCs into HIOs, and (2) deliver HIOs in a synthetic coating to intestinal injuries in vivo. The central hypothesis of this work is that engineering a PEG-based synthetic matrix to support HIO in vitro generation and in vivo delivery will increase the reproducibility, yield, and clinical translatability of this transformative organoid technology.

]]> Laura Paige 1 1638477478 2021-12-02 20:37:58 1638477478 2021-12-02 20:37:58 0 0 event BioE PhD Proposal- "Engineered Synthetic Platform for Human Intestinal Organoid Generation and Delivery " - Adriana Mulero- Russe

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2021-12-15T13:00:00-05:00 2021-12-15T15:00:00-05:00 2021-12-15T15:00:00-05:00 2021-12-15 18:00:00 2021-12-15 20:00:00 2021-12-15 20:00:00 2021-12-15T13:00:00-05:00 2021-12-15T15:00:00-05:00 America/New_York America/New_York datetime 2021-12-15 01:00:00 2021-12-15 03:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Proposal- Sri Krishna Sivakumar]]> 27917 Advisors

Lakshmi Dasi, Ph.D., School of Biomedical Engineering, Georgia Institute of Technology and Emory University  

Dr. John Oshinski, Ph.D., School of Biomedical Engineering, Georgia Institute of Technology and Emory University  

 

Committee Members  

Dr. Ajit P. Yoganathan, Ph.D., School of Biomedical Engineering, Georgia Institute of Technology  

Dr. Brandon Dixon, Ph.D., School of Mechanical Engineering, Georgia Institute of Technology  

Dr. Vinod H. Thourani, M.D., Department of Cardiovascular Surgery, Piedmont Heart Institute  

  

  

Predicting the Biomechanics and risk of coronary obstruction in transcatheter aortic valve replacement using image-based computational modeling 

 

Aortic valve stenosis (AS) is a disease caused by valve degeneration, most commonly due to calcific aortic valve disease, that affects 3% of all adults over 65 years of age and aortic valve replacement (AVR) is the only treatment option for patients with severe AS. Currently, transcatheter based approaches to aortic valve replacement (TAVR) are being widely adopted, especially in patients who are at increased risk of mortality from conventional open-heart surgery. However, adverse procedural complications such as coronary obstruction and aortic root rupture can severely impact the success of TAVR. Despite low incidence of such events, they can present high mortality rates of up to 40% at 30-day follow-up. Pre-procedural cardiac computed tomography (CT) imaging is often insufficient in visualizing the complex interactions between the transcatheter heart valve (THV) stent and the diseased aortic valve. Therefore, reliable prediction of occurrence of these complications based on CT measurements remains a challenge. The goal of this research is to (1) characterize the effects of device type, positioning and procedural adaptations such as valve fracture and alterations to filling volume of balloon-expanded THVs on the biomechanics of THV deployment using a validated computational framework, (2) create a quantitative predictive model for different modes of coronary obstruction and understand the effects of valve type, deployment on the risk of coronary obstruction, and (3) investigate the hemodynamics of coronary ostial flow after TAVR to better understand mechanisms surrounding delayed coronary obstruction using computational fluid dynamics. This study will improve the understanding of biomechanics of TAVR and its adaptations, thus leading to better patient selection. The integration of computational modeling in the procedural planning for TAVR could be the next major step towards reducing the rates of complications and maximize the success rate of TAVR. 

 

]]> Laura Paige 1 1638232654 2021-11-30 00:37:34 1638232654 2021-11-30 00:37:34 0 0 event BioE PhD Proposal- "Predicting the Biomechanics and risk of coronary obstruction in transcatheter aortic valve replacement using image-based computational modeling  " -Sri Krishna Sivakumar

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2021-12-07T13:00:00-05:00 2021-12-07T15:00:00-05:00 2021-12-07T15:00:00-05:00 2021-12-07 18:00:00 2021-12-07 20:00:00 2021-12-07 20:00:00 2021-12-07T13:00:00-05:00 2021-12-07T15:00:00-05:00 America/New_York America/New_York datetime 2021-12-07 01:00:00 2021-12-07 03:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Defense - Venu Ganti]]> 27917 Advisor:
Omer T. Inan, PhD (Georgia Institute of Technology)

 
Committee:
David Frakes, PhD (Georgia Institute of Technology)
Rishikesan Kamaleswaran, PhD (Georgia Institute of Technology)
Jin-Oh Hahn, PhD (University of Maryland, College Park)
Animesh Tandon, MD (Cleveland Clinic Children's Hospital)
 

Enabling Wearable Hemodynamic Monitoring using Multimodal Cardiomechanical Sensing Systems

 

Biomarkers such as blood pressure and stroke volume are instrumental to understanding the pathogenesis of cardiovascular disease. Unfortunately, the monitoring of these hemodynamic parameters is still tethered to in-clinic measurements or is too unaccommodating and inconvenient for ubiquitous use. To address this gap, in this work, we explore seismocardiogram-based wearable multimodal sensing techniques to estimate and enable the use of digital biomarkers—in particular, blood pressure and stroke volume. First, the performance of a multimodal, wrist-worn device capable of obtaining noninvasive pulse transit time measurements is used to estimate blood pressure in an unsupervised, at-home setting. Second, the feasibility of this wrist-worn device is comprehensively evaluated in a diverse and medically underserved population over the course of several perturbations used to modulate blood pressure through different pathways. Finally, the ability of wearable signals—acquired from a custom chest-worn biosensor—to noninvasively quantify stroke volume in patients with congenital heart disease is examined in a hospital setting. Collectively, this work demonstrates the advancements necessary towards enabling noninvasive, longitudinal, and accurate measurements of these biomarkers in remote settings, which offers to advance health equity and disease monitoring in low-resource settings.

 

]]> Laura Paige 1 1637180803 2021-11-17 20:26:43 1637180803 2021-11-17 20:26:43 0 0 event BioE PhD Defense - "Enabling Wearable Hemodynamic Monitoring using Multimodal Cardiomechanical Sensing Systems" - Venu Ganti

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2021-12-01T13:00:00-05:00 2021-12-01T15:00:00-05:00 2021-12-01T15:00:00-05:00 2021-12-01 18:00:00 2021-12-01 20:00:00 2021-12-01 20:00:00 2021-12-01T13:00:00-05:00 2021-12-01T15:00:00-05:00 America/New_York America/New_York datetime 2021-12-01 01:00:00 2021-12-01 03:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Defense- Matthew Cribb]]> 27917 Advisor:
J. Brandon Dixon, PhD (Georgia Institute of Technology)

 
Committee:
Susan Thomas, PhD (Georgia Institute of Technology)
Krishnendu Roy, PhD (Georgia Institute of Technology)
Rudolph Gleason, PhD (Georgia Institute of Technology)
Mark Nicolls, MD (Stanford University School of Medicine)

Investigation of functional lymphatic changes and the immune response during lymphedema development

 

The lymphatic system serves important roles in fluid balance and immune system regulation within the body. Through both passive and active transport of fluid, the lymphatic network transports interstitial fluid back into the circulatory system. When the lymphatic system fails, that excess fluid can no longer be properly transported back into the circulation. This leads to a disease called lymphedema, which manifests as swelling of distal limbs and normally occurs following injury to the lymphatic network. The mechanisms of lymphedema development are not completely understood, but the immune response is known to play an important role in lymphedema pathogenesis. The main goal of this thesis is to investigate both the functional response of the intact lymphatic vasculature and changes in leukocyte populations within draining lymph nodes (dLNs) during lymphedema progression. In the first aim, we used near-infrared (NIR) imaging techniques to quantify changes in lymphatic function in vivo following induction of lymphedema in mice using a novel lymphedema model. We specifically investigated the effect of two potential therapeutic mechanisms, antagonism of leukotriene B4 (LTB4) production and deletion of epsin, on lymphatic function following lymphedema surgery. Further in vivo and ex vivo analysis was performed to elucidate potential mechanisms regulating the effect of LTB4 on lymphatic contractile function. In the second aim, we used flow cytometry to investigate changes in leukocyte populations within dLNs during acute lymphedema progression. Our novel lymphedema model leaves a pair of intact collecting lymphatic vessels on one side of the mouse tail while other tail lymphatics are ligated, allowing for analysis of the immune response within dLNs experiencing differences in drainage. Further analysis using a nanoparticle delivery system was used to quantify differences in particle uptake between dLNs as lymphedema progressed. The effect of LTB4 antagonism on the immune response was also elucidated. Overall, this work furthers understanding of the mechanisms driving lymphedema pathogenesis, by combining comprehensive analysis of changes in lymphatic contractile function in vivo and ex vivo with investigation of changes in the immune response within dLNs.

]]> Laura Paige 1 1637180562 2021-11-17 20:22:42 1637180562 2021-11-17 20:22:42 0 0 event BioE PhD Defense- "Investigation of functional lymphatic changes and the immune response during lymphedema development"- Matthew Cribb

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2021-12-01T13:30:00-05:00 2021-12-01T15:03:00-05:00 2021-12-01T15:03:00-05:00 2021-12-01 18:30:00 2021-12-01 20:03:00 2021-12-01 20:03:00 2021-12-01T13:30:00-05:00 2021-12-01T15:03:00-05:00 America/New_York America/New_York datetime 2021-12-01 01:30:00 2021-12-01 03:03:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Proposal - Tong Yu]]> 27917 Advisor:

Prof. Todd Sulchek (School of Mechanical Engineering, Georgia Institute of Technology)

Committee:

Prof. Sunil Raikar (School of Medicine, Winship Cancer Institute, Emory University))

Prof. James Dahlman (School of Biomedical Engineering, Georgia Institute of Technology)

Prof. Wilbur Lam (School of Biomedical Engineering, Georgia Institute of Technology)

Prof. Gabriel Kwong (School of Biomedical Engineering, Georgia Institute of Technology)

 

A biomechanics-based delivery strategy to primary immune cells for generating allogeneic cell therapy with multiple gene knockout

 

Genetically engineered immune cells, such as those used in Chimeric Antigen Receptor-modified (CAR) T cell therapy and T Cell Receptor-modified (TCR-T) T cell therapy, have transformed the treatment of oncological diseases. Yet manufacturing of cell therapies faces challenges, including low scalability, inefficient workflow, and high production cost. Allogeneic T cell products, in which cells are sourced from healthy donors, genetically modified, and supplied to multiple patients, will greatly reduce the cost of manufacturing and shorten the treatment regimen. Manufacturing process for allogenic CAR-T and TCR-T cells requires genetic knockout of multiple genes related to foreign antigen presentation and recognition to improve safety and persistency of infused cells. Additionally, gene editing has been applied in negative regulator (e.g., PD1) knockout to improve CAR-T function against solid tumor, and in shared target antigen knockout to reduce CAR-T cell fratricide.  These applications demand a more efficient and safer strategy for gene reprogramming, which is unmet by current methods.

CRISPR/Cas9 system is a powerful choice of gene reprogramming system. Because Cas9 protein induces DNA double stranded breaks (DSB) at targeted loci, multiplexed cas9/gRNA delivery in one batch increases the possibility of chromosomal deletion and translocation, leading to genetic instability. A TCR-T cells carrying triple edits had 1-4% of cells harboring chromosomal translocation. These cells pose a direct safety concern to patients and lead to low in vivo fitness and persistence that results in low long-term potency. Therefore, a new gene editing workflow is needed to reduce incidence of multiple DSB.

The goal of this research project is to test a microfluidic cell transfection technology with the potential to permit multiple CRISPR edits with high transfection efficiency and viability, and minimal negative impact on genome stability and therapeutic potency. To achieve this goal, the proposed study will apply a microfluidic Volume Exchange for Convective Transfection (VECT) platform for biomechanical transfections. This study pursues 3 aims:

Aim 1: Optimize VECT device for efficient delivery to primary T cells. We will test various device design and fabrication method to achieve optimal transfection and cell viability. 

Aim 2: Demonstrate new editing workflows consisting of sequential triple gene editing and test impact on genome stability and CAR-T cell potency. We will evaluate VECT’s ability to enable consecutive single gene knockout to avoid generating multiple DSB.

Aim 3: Relate biomechanical features of T cell to transfection outcome. We will test the hypothesis that VECT preferentially deliver to cells with certain mechanical features, and altering mechanics can improve transfection.

]]> Laura Paige 1 1637180289 2021-11-17 20:18:09 1637180289 2021-11-17 20:18:09 0 0 event BioE PhD Proposal -  "A biomechanics-based delivery strategy to primary immune cells for generating allogeneic cell therapy with multiple gene knockout"- Tong Yu

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2021-12-01T10:00:00-05:00 2021-12-01T12:00:00-05:00 2021-12-01T12:00:00-05:00 2021-12-01 15:00:00 2021-12-01 17:00:00 2021-12-01 17:00:00 2021-12-01T10:00:00-05:00 2021-12-01T12:00:00-05:00 America/New_York America/New_York datetime 2021-12-01 10:00:00 2021-12-01 12:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[MS Thesis Presentation- Nina Sara Fraticelli-Guzmán]]> 27917 Advisor:

Craig Forest, PhD

School of Mechanical Engineering

Georgia Institute of Technology

 

Committee members:

David Hu, PhD

School of Mechanical Engineering

Georgia Institute of Technology

 

Michael Farrell, PhD

Georgia Tech Research Institute (GTRI)

Georgia Institute of Technology

 

 

Quantitative assessment of methods for bacterial and viral purification and concentration

From water pathogen detection, SARS-CoV-2 detection, to biological weapon detection, the samples we analyze include much more than our target organism. To accurately detect our targets of choice, the use of various labor intensive, and at times costly techniques, have been used to purify and concentrate the target organism. In this work, we evaluate quick and easily implementable techniques for viral and bacterial purification and concentration. These methods are more cost effective and amenable towards automation, allowing for a decrease in not just cost, but also labor time. The research presented here characterizes the applicability of syringe filters and a tangential flow filtration device for the purification and concentration of bacteria and virus samples, respectively. Furthermore, automation of such systems were explored. We developed a fully automated method for double filter filtration to enable hands-free purification and concentration of bacteria in 5.5 minutes from 5 mL of input volume yielding a 42 ± 13-fold enrichment improvement (n = 3). Furthermore, the purification and concentration of virus using a manually operated tangential flow filtration device was also explored and yielded modest concentration increases of around 2 with a 1,916 ± 1,839-fold  (n = 3) enrichment improvement under one configuration.

 

]]> Laura Paige 1 1637179980 2021-11-17 20:13:00 1637179980 2021-11-17 20:13:00 0 0 event MS Thesis Presentation "Quantitative assessment of methods for bacterial and viral purification and concentration"- Nina Sara Fraticelli-Guzmán

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2021-12-01T15:00:00-05:00 2021-12-01T17:00:00-05:00 2021-12-01T17:00:00-05:00 2021-12-01 20:00:00 2021-12-01 22:00:00 2021-12-01 22:00:00 2021-12-01T15:00:00-05:00 2021-12-01T17:00:00-05:00 America/New_York America/New_York datetime 2021-12-01 03:00:00 2021-12-01 05:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Proposal- Isaac Robinson]]> 27917 Advisor:

Prof. Susan Thomas (School of Mechanical Engineering, Georgia Institute of Technology)

Committee:

Prof. Shuichi Takayama (School of Biomedical Engineering, Georgia Institute of Technology)

Prof. Edward Botchwey (School of Biomedical Engineering, Georgia Institute of Technology)

Prof. Adam Marcus (School of Medicine, Winship Cancer Institute, Emory University)

Prof. Andrés Garcia (School of Mechanical Engineering, Georgia Institute of Technology)


 

Engineering method for characterization of dynamic cell migration with application for cancer metastasis investigation

 

Novel methods for understanding cell migration are constantly being engineered. However, such tools, while embraced by engineers, have not seen similar levels of adoption by mainstream biology research. There is, therefore, a need to develop not only useful investigational tools, but those that will also be largely accepted/implemented in biological studies. Despite the numerous microfluidic devices that have been recently developed by engineers specifically for biological or medical investigation, many biological and medical researchers have continued with conventional assays or in vivo studies. To address this, one such conventional assay was identified and enhanced: a simple but ubiquitously used technology in biology for understanding chemotaxis called the Boyden chamber assay (BCA). Rather than design a microfluidic system that more efficiently and precisely does the job of this assay, but with engineering complexities that might deter non-engineers from adoption, it could be more impactful to couple the platform with simple but enhancing technology. Thus, the overall objective is to design a system that combines the ubiquity of BCAs with the high throughput, high resolution analysis capability of a cell photoconversion system in order to provide single cell resolution of transmigration over time. The central hypothesis is that the development of a platform with the capacity to fluorescently tag a cell based on the time at which it first migrates will provide key insights into dynamic migration characteristics that relate to individual cellular protein expression of cancer cells in varied metastatic-mimicking microenvironments. Understanding single cell behavior in this way will provide insight into metastatic cancer progression for use in development of migrastatic therapy. Beyond the direct impact in cancer research, this work will provide a method that can be implemented across many fields involving cell migration to investigate heterogenous cell migration dynamics at high resolution.

]]> Laura Paige 1 1637074340 2021-11-16 14:52:20 1637074340 2021-11-16 14:52:20 0 0 event BioE PhD Proposal- " Engineering method for characterization of dynamic cell migration with application for cancer metastasis investigation" - Isaac Robinson

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2021-11-29T11:00:00-05:00 2021-11-29T13:00:00-05:00 2021-11-29T13:00:00-05:00 2021-11-29 16:00:00 2021-11-29 18:00:00 2021-11-29 18:00:00 2021-11-29T11:00:00-05:00 2021-11-29T13:00:00-05:00 America/New_York America/New_York datetime 2021-11-29 11:00:00 2021-11-29 01:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Proposal- Breandan Yeats]]> 27917 Advisor: 

Lakshmi Dasi, Ph.D. (School of Biomedical Engineering, Georgia Institute of Technology) 

Committee:  

Ajit Yoganathan, Ph.D. (School of Biomedical Engineering, Georgia Institute of Technology) 

John Oshinski, Ph.D. (School of Biomedical Engineering Georgia Institute of Technology and Emory University) 

Rudy Gleason, Ph.D. (School of Mechanical Engineering, Georgia Institute of Technology) 

Vinod H. Thourani, MD. (Department of Cardiovascular Surgery, Piedmont Heart Institute ) 

 

Biomechanics of Transcatheter Aortic Valve Replacement for Bicuspid Aortic Valves 

  

Bicuspid aortic valve (BAV) is the most common congenital heart defect and is associated with numerous pathologies including calcific aortic valve disease (CAVD) which requires replacement of the native valve. Replacements are delivered through either surgical or transcatheter aortic valve replacement (TAVR) approaches. The number of TAVR in BAV cases is expected to increase substantially due to the recent removal of the FDA precautionary label for TAVR use in BAV patients and deemed safe in low-surgical risk patients. Two of the main concerns when treating BAV patients with TAVR are paravalvular regurgitation (PVR), a known associate of increased patient mortality, and long-term durability. Highly calcified BAV patients have shown increased incidence of PVR following TAVR. Additionally, stent asymmetry and undersizing are common in BAV patients both being indicators of reduced device durability however, very limited data exists on TAVR long-term durability in BAV patients. Determining the risk of these complications based on BAV anatomy is very difficult as current morphology classification systems do not encompass all aspects of the anatomy and there is limited data correlating anatomy to these outcomes beyond calcium scoring. The impact of device placement and balloon filling volume across varying BAV anatomies is also not fully understood. This research aims to (1) quantify the BAV anatomy and create a new quantitative parameterized aortic valve classification system, (2) assess BAV anatomical relationship to PVR, stent asymmetry, bioprosthetic leaflet stress, and bioprosthetic leaflet opening after TAVR, (3) evaluate the impact of TAVR placement and balloon filling volume on PVR, stent asymmetry, bioprosthetic leaflet stress, and bioprosthetic leaflet opening after TAVR. This study will be extremely valuable in understanding the aortic valve anatomy pertaining to different morphologies and the biomechanics of TAVR for BAV patients leading to more informed patient selection for TAVR and TAVR planning. 

]]> Laura Paige 1 1636740290 2021-11-12 18:04:50 1636740290 2021-11-12 18:04:50 0 0 event BioE PhD Proposal- "Biomechanics of Transcatheter Aortic Valve Replacement for Bicuspid Aortic Valves " -Breandan Yeats

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<![CDATA[BioE PhD Proposal Presentation- Andrew Short]]> 27917 Advisor: 

Corey Wilson, Ph.D. (Chemical & Biomolecular Engineering, Georgia Institute of Technology) 

Committee:  

Ravi Kane, Ph.D. (School of Chemical & Biomolecular Engineering, Georgia Institute of Technology) 

Manu Platt, Ph.D. (School of Biomedical Engineering, Georgia Institute of Technology) 

Matthew Realff, Ph.D. (School of Chemical & Biomolecular Engineering, Georgia Institute of Technology) 

Eric Vogel, Ph.D. (School of Materials Science & Engineering, Georgia Institute of Technology) 

 

Next-Generation Genetic Memory for Synthetic Biology Applications 

  

Synthetic biology seeks to mine engineerable components from complex natural biological systems and reapply them in a way that is amenable to predictive design and other engineering approaches, eventually developing new, useful applications. A significant gap in this approach is an ability to perform biological memory operations (genetic manipulations that permanently store the results of biological information-processing operations) efficiently and controllably. Site-specific recombinases are enzymes that catalyze permanent DNA rearrangements at specific DNA sequences, making them prime targets for use in biological memory circuits. However, these enzymes can be difficult to employ because only a small number of traditional genetic regulatory parts can effectively regulate their expression. We hypothesize that using DNA-binding transcription factors (TFs) to sterically block the function of recombinases at their target DNA sequences will enable finer control over recombinase activity, a novel strategy we term “interception”. To investigate this hypothesis, we will build and test genetic memory circuits that apply interception to fluorescent reporter genes in E. coli. Aim 1 will demonstrate the feasibility and efficacy of this approach on single-input deletion circuits. Aim 2 will develop multi-input memory information processing. Aim 3 will exploit a characteristic of recombinase-binding DNA sequences to generate up to six independent memory operations per recombinase, culminating in the development of a novel one-recombinase, seven-input memory array. Interception will enable stronger control over recombinase expression, reduced metabolic burden from their use, and the creation of more complex genetic memory operations.  

]]> Laura Paige 1 1634933313 2021-10-22 20:08:33 1634933313 2021-10-22 20:08:33 0 0 event BioE PhD Proposal Presentation-  "Next-Generation Genetic Memory for Synthetic Biology Applications" - Andrew Short

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<![CDATA[BioE PhD Proposal Presentation- Sri Krishna Sivakumar ]]> 27917 Advisor: Lakshmi Dasi, Ph.D., School of Biomedical Engineering, Georgia Institute of Technology  

  

Committee Members:   

Ajit P. Yoganathan, Ph.D., School of Biomedical Engineering, Georgia Institute of Technology  

John Oshinski, Ph.D., School of Biomedical Engineering, Georgia Institute of Technology and Emory University  

Brandon Dixon, Ph.D., School of Mechanical Engineering, Georgia Institute of Technology  

Vinod H. Thourani, M.D., Department of Cardiovascular Surgery, Piedmont Heart Institute  

  

  

Predictive Computational Modeling of Transcatheter Aortic Valve Replacement

 

Aortic valve stenosis (AS) is a disease caused by valve degeneration, most commonly due to calcific aortic valve disease that affects 3% of all adults over 65 years of age. Based on severity, the aortic valve is replaced by a bioprosthetic aortic valve, either surgically or using a transcatheter approach. Currently, transcatheter based approaches to aortic valve replacement (TAVR) are being widely adopted, especially in patients who are at increased risk of mortality with conventional open-heart surgery. However, adverse procedural complications such as coronary obstruction and aortic root rupture can severely impact the success of the procedure. Despite the low incidence of such adverse outcomes after TAVR, they can present high mortality rates of up to 40% at 30-day follow-up. The biomechanics of TAVR complications are not fully understood. Pre-procedural cardiac computed tomography (CT) imaging is often insufficient in visualizing the complex interactions between the bioprosthetic stent and diseased aortic valve and therefore, reliable prediction of occurrence of these complications based on CT measurements remains a challenge. The goal of the proposed research is to develop a patient specific computational framework for TAVR, that is validated using post-procedural clinical imaging data, for use in risk assessment & planning to improve patient selection for TAVR. Finite element methods and computational fluid dynamics will be used to create the predictive models for simulating TAVR in patient specific geometries and for quantitative risk assessment of coronary obstruction. An in vitro flow simulator that allows for reliable reproduction of in vivo conditions in patient specific 3D printed geometries, as well as retrospective procedural outcomes, will be used to validate results from computational modeling and improve the robustness of the prediction. The integration of computational modeling in procedural planning could be the next major step towards reducing rates of complications and maximizing the success of TAVR.

]]> Laura Paige 1 1634051359 2021-10-12 15:09:19 1634051359 2021-10-12 15:09:19 0 0 event BioE PhD Proposal Presentation- "Predictive Computational Modeling of Transcatheter Aortic Valve Replacement" -  Sri Krishna Sivakumar  

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<![CDATA[BioE PhD Proposal Presentation- Hannah Viola]]> 27917 Advisor:

Shuichi Takayama, PhD (Department of Biomedical Engineering, Georgia Institute of Technology)

Committee: 

Hang Lu, PhD (School of Chemical & Biomolecular Engineering, Georgia Institute of Technology)

Andrés García, PhD (School of Mechanical Engineering, Georgia Institute of Technology)

Dr. Jocelyn Grunwell (Emory CHOA/Pediatrics) 

Dr. Rabindra Tirouvanziam (Emory Pediatrics) 

 

A functional assay of neutrophil recruitment and activation for immunomodulatory drug screening

 

This project will develop a functional cell-based assay for testing neutrophil-targeted therapeutics. We apply the assay to understand patient-specific differences in response to drugs for pediatric acute respiratory distress syndrome (PARDS). We hypothesize that therapeutics targeting neutrophil activation will elicit heterogeneous responses depending on the patient’s pathobiological features, specifically tracheal aspirate cytokine concentrations. First, we will validate the assay conditions for precise, reliable detection of drug responses. Therefore, we will mitigate sample dilution effects, define a positive control condition, and optimize the timing of each assay step. With these parameters, we will proceed to evaluate 3 immunomodulatory drugs in a trial cohort of 6 patients with severe PARDS: IL-6 receptor antagonist Tocilizumab, IL-1 receptor antagonist Anakinra, and JAK/STAT inhibitor Baricitinib. We expect drug response heterogeneity due to variable patient-specific cytokine profiles in the tracheal aspirate that neutrophils are primed and recruited to during our assay. We will therefore compare the drug response of each patient to the initial concentration of 21 tracheal aspirate cytokines to determine whether drug responses are related to cytokine profiles in our assay. Ultimately, this platform will enable the identification of “likely-responder” patients who couldbe treated with targeted interventions or enrolled in trials for anti-neutrophil therapy.

]]> Laura Paige 1 1634050800 2021-10-12 15:00:00 1634050800 2021-10-12 15:00:00 0 0 event BioE PhD Proposal Presentation- "A functional assay of neutrophil recruitment and activation for immunomodulatory drug screening" -Hannah Viola

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<![CDATA[Bioengineering Seminar Series]]> 27195 Virtual event - REGISTER here for participation link

"Genome Folding, Unfolding, and Refolding in the Human Brain"

Jennifer Phillips-Cremins, Ph.D.
Associate Professor
Dean’s Faculty Fellow in Engineering and Medicine New York Stem Cell Foundation
Robertson Investigator Department of Genetics
Perelman School of Medicine Department of Bioengineering
School of Engineering and Applied Sciences
University of Pennsylvania 


RESEARCH
The Cremins lab investigates the epigenetic mechanisms regulating development and function of the mammalian central nervous system. We map and analyze neuronal epigenomes in three-dimensions using quantitative, genome-wide technologies. We also perturb epigenomes by employing state-of-the art genetic engineering strategies (e.g. CRISPR/Cas9, optoepigenetics). To test our hypotheses, we primarily use embryonic and induced pluripotent stem cell models of neuronal differentiation and disease. Our long-term goal is to discover how genome architecture controls genome function, applying this to study fundamental mechanisms controlling neuronal phenotype and, by extension, the onset and progression of neurodegenerative and neurodevelopmental disease states.

BIO
Jennifer Phillips-Cremins, Ph.D. is an Associate Professor and Deans' Faculty Fellow in Engineering and Medicine at the University of Pennsylvania with primary appointments in the Departments of Bioengineering and Genetics. Dr. Cremins obtained her Ph.D. in Biomedical Engineering from the Georgia Institute of Technology in the laboratory of Andres Garcia. She then conducted a multi-disciplinary postdoc in the laboratories of Job Dekker and Victor Corces. Dr. Cremins now runs the Chromatin Architecture and Systems Neurobiology laboratory at UPenn. Her primary research interests lie in understanding the long-range chromatin architecture mechanisms that govern neural specification and synaptic plasticity in healthy neurons and how these epigenetic mechanisms go awry in neurodevelopmental and neurodegenerative diseases. She has been selected as a 2014 New York Stem Cell Foundation Robertson Investigator, a 2015 Albert P. Sloan Foundation Fellow, a 2016 and 2018 Kavli Frontiers of Science Fellow, 2015 NIH Director's New Innovator Awardee, 2020 NSF CAREER Awardee, and a 2020 CZI Neurodegenerative Disease Pairs Awardee.

]]> Colly Mitchell 1 1623334951 2021-06-10 14:22:31 1631202776 2021-09-09 15:52:56 0 0 event 2021-09-09T13:00:00-04:00 2021-09-09T14:00:00-04:00 2021-09-09T14:00:00-04:00 2021-09-09 17:00:00 2021-09-09 18:00:00 2021-09-09 18:00:00 2021-09-09T13:00:00-04:00 2021-09-09T14:00:00-04:00 America/New_York America/New_York datetime 2021-09-09 01:00:00 2021-09-09 02:00:00 America/New_York America/New_York datetime <![CDATA[]]> Karmella Haynes, Ph.D. - faculty host
Rose Brito - event inquiries

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<![CDATA[BioEngineering Graduate Committee Meeting]]> 27917 The BioEngineering graduate committee will meet to review/approve program policies, program faculty applications and submitted student petitions.

]]> Laura Paige 1 1612803342 2021-02-08 16:55:42 1631027437 2021-09-07 15:10:37 0 0 event BioEngineering Graduate Committee Meeting

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2021-09-30T13:00:00-04:00 2021-09-30T14:00:00-04:00 2021-09-30T14:00:00-04:00 2021-09-30 17:00:00 2021-09-30 18:00:00 2021-09-30 18:00:00 2021-09-30T13:00:00-04:00 2021-09-30T14:00:00-04:00 America/New_York America/New_York datetime 2021-09-30 01:00:00 2021-09-30 02:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Proposal Presentation- Alexander Beach]]> 27917 Advisor:

Dr. Krishnendu Roy, Ph.D., Department of Biomedical Engineering, Georgia Institute of Technology and Emory University

 

Committee Members:

Dr. Andrés García, Ph.D., School of Mechanical Engineering, Georgia Institute of Technology

Dr. Erik Dreaden, Ph.D., Department of Biomedical Engineering, Georgia Institute of Technology and Emory University

Dr. Valeria Milam, Ph.D., School of Materials Science and Engineering, Georgia Institute of Technology

Dr. Susan N. Thomas, Ph.D., School of Mechanical Engineering, Georgia Institute of Technology

 

Investigating the Underlying Mechanisms of the Immune Response to Chitosan-Derived Combinatory Adjuvant Nanoparticles

The two critical components of subunit vaccines are antigen and adjuvant selection, the former specific to the pathogen, the latter specific to the desired immune response. One of the most used adjuvants is alum, a general-purpose adjuvant comprised of various aluminum salts that can form particle-like complexes with antigen. As this type of adjuvant continues to be widely used, there is a continual gap in knowledge about adjuvants that target more specific, individual pathways of the immune system, especially when used in tandem. From its role as a STING agonist, to its electrostatic methods of adsorbing other adjuvants, chitosan is a very similar material to alum for this application. Furthermore, this shellfish-derived protein also can be further modified with imidazoleacetic acid (IAA) for the purpose of facilitating endosomal escape and lowering toxicity. This research proposal aims to investigate the response to administering chitosan nanoparticles, both with and without IAA modification, loaded with other, more specific adjuvants to better understand the underlying mechanisms therein. By using two common murine bone marrow-derived cell culture methods, we have shown that differences in cell culture environment can affect this response, even demonstrating a complete pathway shift for type I interferon secretion. In terms of future in vivo studies, the viability of these particles as a vaccine towards a pathogen of therapeutic interest will be assessed, alongside the molecular mechanisms of the resulting immune response and biodistribution. Through this research, we hope to further knowledge on the topic of combinatorial adjuvants, while also presenting a viable alternative to alum as an electrostatically driven adjuvant particle system for vaccines.

]]> Laura Paige 1 1628783970 2021-08-12 15:59:30 1628783970 2021-08-12 15:59:30 0 0 event BioE PhD Proposal Presentation-  "Investigating the Underlying Mechanisms of the Immune Response to Chitosan-Derived Combinatory Adjuvant Nanoparticles"- Alexander Beach

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<![CDATA[BioE PhD Proposal Presentation- Shelley Gooden]]> 27917 Advisor: Lakshmi Dasi, Ph.D., School of Biomedical Engineering, Georgia Institute of Technology 

 

Committee Members 

Dr. Ajit P. Yoganathan, Ph.D., School of Biomedical Engineering, Georgia Institute of Technology 

Dr. Mularidhar Padala, Ph.D., School of Biomedical Engineering, Georgia Institute of Technology and Emory University 

Dr. Brandon Dixon, Ph.D., School of Mechanical Engineering, Georgia Institute of Technology 

Dr. Vinod H. Thourani, M.D., Department of Cardiovascular Surgery, Piedmont Heart Institute 

Dr. Konstantinos Dean Boudoulas, M.D., Division of Cardiovascular Medicine, The Ohio State University Wexner Medical Center 

 

Predicting Biomechanical Implications of Transcatheter Atrioventricular Valve Interventions

Mitral and tricuspid regurgitation are common valvular disorders in the United States, with 1.7% of the general population and 9.3% of those age 75 years and older having mitral regurgitation and 1.6 million with at least moderate tricuspid regurgitation. For those deemed high-risk for surgical treatment by a heart team, minimally invasive transcatheter therapies can be used. Therapies include transcatheter edge-to-edge repair and transcatheter valve replacement. While clinical results show promising outcomes, fluid mechanic implications of post-operative hemodynamics are not fully understood. This research proposal aims to study pre- and post-intervention hemodynamics, including diastolic ventricular flow velocity and vorticity, fluid stresses, valve and outflow tract pressure gradient and recovery, effective orifice area, and particle washout, with the goal of developing predictive algorithms. An in vitro flow set-up allowing reliable reproduction of in vivo conditions will be used to assess these parameters on parameterized and patient-specific anatomies as well as on animal valves. Both engineering and clinical techniques will be used, such as particle image velocimetry and echocardiography. Studying how these hemodynamic parameters are effected by transcatheter repair and replacement can improve clinician knowledge in device selection for patients in need of transcatheter mitral and/or tricuspid valve therapy.

]]> Laura Paige 1 1626286447 2021-07-14 18:14:07 1626286447 2021-07-14 18:14:07 0 0 event BioE PhD Proposal Presentation- "Predicting Biomechanical Implications of Transcatheter Atrioventricular Valve Interventions" - Shelley Gooden

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<![CDATA[BioE PhD Proposal Presentation- Lucinda Peng]]> 27917 Advisor: Hang Lu, Ph.D.
School of Chemical & Biomolecular Engineering, Georgia Institute of Technology

 

Committee members:
Daniel Goldman, Ph.D.
School of Physics, Georgia Institute of Technology
Patrick McGrath, Ph.D.
School of Biological Sciences, Georgia Institute of Technology
Simon Sponberg, Ph.D.
School of Physics, Georgia Institute of Technology
Lena Ting, Ph.D.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology

 

Engineered imaging and behavior assays to study effects of genes and environment on neurodegeneration
Environmental and genetic factors are two main contributors to disease pathology, including neurodegeneration. In particular, particulate matter exposure has been linked with many adverse health effects, including Parkinson's disease. However, the diversity of genetic backgrounds and environmental exposures make the link between the two hard to study in humans. We use the model organism, C. elegans to tightly control genetic background and environmental exposure and measure the resulting neurodegeneration. Existing systems cannot monitor the development and neurodegeneration of individuals. This work will focus on the effect of traffic-related PM exposure on Parkinson's disease related neurodegeneration and behavioral decline. The objective of my thesis is to engineer a system which can record the long-term development and behavior of worms during exposure to oxy-PAH, measure the subsequent neurodegeneration through a physically challenging assay which requires sensorimotor integration, and assess the functional integrity of neurons and link that to changes in behavior. This system will allow for linking environmental toxins with cellular stress mechanisms, neural degeneration, and behavior of individuals.

]]> Laura Paige 1 1626286277 2021-07-14 18:11:17 1626286277 2021-07-14 18:11:17 0 0 event BioE PhD Proposal Presentation- "Engineered imaging and behavior assays to study effects of genes and environment on neurodegeneration" - Lucinda Peng

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2021-07-15T14:00:00-04:00 2021-07-15T16:00:00-04:00 2021-07-15T16:00:00-04:00 2021-07-15 18:00:00 2021-07-15 20:00:00 2021-07-15 20:00:00 2021-07-15T14:00:00-04:00 2021-07-15T16:00:00-04:00 America/New_York America/New_York datetime 2021-07-15 02:00:00 2021-07-15 04:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Defense Presentation- Mark Stathos]]> 27917 Advisor:  

Ravi Kane, Ph.D.  (ChBE, Georgia Institute of Technology) 

   

Committee Members:   

Andres García, Ph.D. (ME, Georgia Institute of Technology) 

Manu Platt, Ph.D. (BME, Georgia Institute of Technology) 

Todd Sulchek, Ph.D. (ME, Georgia Institute of Technology) 

Ronghu Wu, Ph.D.  (Chemistry and Biochemistry, Georgia Institute of Technology) 

  

Engineering Tools to Promote and Characterize Wnt-Mediated Stem Cell Differentiation 

The Wnt signaling pathway plays an important role in the development of many tissues in the body, notably cardiac tissue, from the very earliest stage of the process. However, the precise mechanisms of the Wnt pathway and the specific roles it has in development in the context of different tissue types remain poorly understood. This is in part due to the complexity of embryonic development and in part due to the hydrophobicity of Wnt ligands which renders them expensive and difficult to purify in a usable form.  

              To overcome issues associated with the use of natural Wnt ligands, we have developed a heterodimer of Fabs which bind to the Wnt co-receptors LRP6 and Frizzled. We have demonstrated that this dimer can activate Wnt signaling with an efficacy comparable to that of the natural ligand.  

              To elucidate the mechanisms of downstream events in the Wnt pathway, we constructed a kinetic model consisting of a system of ordinary differential equations. We fit this model to empirical time course data derived from Western blots of HEK293T cells treated with Wnt. From this fit we were able to gain insights into how the intracellular levels of the Wnt pathway component β-catenin are regulated. 

              To better characterize the downstream effects of Wnt signaling during the manufacturing of therapeutic cells, we are also generating CRISPR/Cas9 edited reporter iPSC lines which we hope will be able to detect the expression of Wnt-regulated marker genes such as Brachyury and COUP-TFII with high specificity. Luminescent signals secreted by these cell lines during directed differentiation into cardiomyocytes will permit continuous non-destructive monitoring of the manufacturing process. These cell lines could potentially guide process optimization and enable production of cardiomyocytes with a more mature phenotype. These cells will also be equipped with an inducible suicide mechanism to enable their removal during cell manufacturing applications involving co-culture with unedited cells. 

]]> Laura Paige 1 1626286097 2021-07-14 18:08:17 1626286097 2021-07-14 18:08:17 0 0 event BioE PhD Defense Presentation-  "Engineering Tools to Promote and Characterize Wnt-Mediated Stem Cell Differentiation " - Mark Stathos

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<![CDATA[BioE PhD Proposal Presentation- Pawel Goylski]]> 27917 Advisor: 

Gregory S. Sawicki, Ph.D. 

 

Committee: 

T. Richard Nichols, Ph.D. (Georgia Institute of Technology) 

Lena H. Ting, Ph.D. (Georgia Institute of Technology, Emory University) 

Young-Hui Chang, Ph.D. (Georgia Institute of Technology) 

Keith E. Gordon, Ph.D. (Northwestern University) 

 

Tuning biomechanical energetics with an exoskeleton to improve stability during walking 

 

Wearable robots such as exoskeletons can be powerful tools for helping an individual accomplish different objectives during locomotion, such as improving economy (“gas mileage”), increasing strength, or enhancing stability. The latter objective remains a major unmet public health challenge – falls during walking account for 68% of injuries in the workplace, and 1 in 4 older adults fall each year. Most falls occur because of a destabilizing exchange of mechanical energy between a person and their environment, such as a trip or slip. In terrestrial vertebrates, distal joints and muscles, such as the ankle and plantarflexors, act as dampers to dissipate energy injected by perturbations such as unexpected drops in terrain height. While the hip joint and associated muscles are considered the “motors” of the lower limb during steady locomotion, the role of proximal joints and muscles in responding to perturbations that demand energy generation is unknown. The first aim of the proposed work is to determine the hip’s response, from joint to muscle levels, in responding to destabilizing mechanical energy demands. Elastic exoskeletons could improve stability by tuning biological structures to better perform their energetic roles. Since elastic hip exoskeletons have demonstrated an ability to increase biological mechanical work output at the hip, for perturbations that demand mechanical energy generation elastic exoskeletons may provide a physiology-based approach to improving stability. Thus, the second aim of the proposed work is to evaluate the influence of an elastic hip exoskeleton on stability following transient mechanical energy demands. Together, the completion of the proposed aims will improve our understanding of the role of proximal joints and muscles in the unstable contexts of daily life and can provide the basis for the development of a new generation of bioinspired stability-enhancing exoskeletons. 

]]> Laura Paige 1 1621779783 2021-05-23 14:23:03 1621779783 2021-05-23 14:23:03 0 0 event BioE PhD Proposal Presentation- " Tuning biomechanical energetics with an exoskeleton to improve stability during walking "- Pawel Goylski

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<![CDATA[BioE PhD Proposal Presentation- Rebecca Schneider]]> 27917 Advisor: 

Andrés J. García, Ph.D.

George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology

  

Committee Members:  

  

John Blazeck, Ph.D.

School of Chemical & Biomolecular Engineering, Georgia Institute of Technology

 

Ankur Singh , Ph.D.

George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology

 

Wilbur Lam, Ph.D., MD

Division of Hematology/Oncology, Department of Pediatrics, Emory University

 

Ross Marklein, Ph.D.

School of Chemical, Materials, and Biomedical Engineering, University of Georgia

 

High-throughput microfluidic potency assay for human mesenchymal stromal cell products with clinical prediction

Human mesenchymal stromal cells (MSC) are a promising source for regenerative cell therapy. However, MSC market access has been stymied by product variability across MSC donors and manufacturing practices resulting in inconsistent clinical outcomes. The inability to predict MSC in vivo performance is a major limitation of MSC market penetration. Standard metrics of MSC potency employ MSC:peripheral blood mononuclear cell (PBMC) co-cultures, however, these assays are challenging to scale due to high PBMC donor variability. To address this challenge, I present a high-throughput, scalable, low-cost microfluidic MSC potency assay with improved MSC secretory correlation to in vivo performance. Traditional planar potency assays have been largely unsuccessful for MSC clinical translation. I demonstrate improved predictive power of the microfluidic platform compared to traditional planar methods by comparison of MSC secretory responses to PBMC co-culture assays. Further, I show analogous MSC secretory performance achieved in the microfluidic platform compared to an in vivo model. Lastly, with early promising results, I am now performing microfluidic potency assay validation by testing clinical samples from the multicenter MILES osteoarthritis clinical study for further system optimization and clinical validation.

 

]]> Laura Paige 1 1620831424 2021-05-12 14:57:04 1620831424 2021-05-12 14:57:04 0 0 event BioE PhD Proposal Presentation- "High-throughput microfluidic potency assay for human mesenchymal stromal cell products with clinical prediction" - Rebecca Schneider

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2021-05-27T11:00:00-04:00 2021-05-27T13:00:00-04:00 2021-05-27T13:00:00-04:00 2021-05-27 15:00:00 2021-05-27 17:00:00 2021-05-27 17:00:00 2021-05-27T11:00:00-04:00 2021-05-27T13:00:00-04:00 America/New_York America/New_York datetime 2021-05-27 11:00:00 2021-05-27 01:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Defense Presentation- Justin Lee]]> 27917 Advisor: 

Mark P. Styczynski, Ph.D.  (ChBE, Georgia Institute of Technology)

  

Committee Members:  

Fani Boukouvala, Ph.D. (ChBE, Georgia Institute of Technology)

Melissa Kemp, Ph.D. (BME, Georgia Institute of Technology)

Andrew Medford, Ph.D. (ChBE, Georgia Institute of Technology)

Eberhard Voit, Ph.D.  (BME, Georgia Institute of Technology)

 

Computational modeling of metabolic pathways toward predicting dynamic phenotypes

Metabolic systems are important to a wide variety of applications, including therapeutic development, agricultural crop production, and manufacturing of industrial chemicals. Developing metabolic models is one of the best approaches to study metabolism, as computational experiments are generally cheaper and faster to perform than experiments in a laboratory. While there are computational frameworks that can model large metabolic systems at steady state or the metabolite dynamics of a small number of key metabolic pathways, it is substantially more difficult to model the dynamics of metabolism at the genome scale. In this thesis dissertation, I present three computational platforms that address several of the challenges in developing dynamic genome-scale metabolic models. First, I devised a stepwise machine learning strategy for identifying the regulatory topology within metabolic systems, which can be used to construct more accurate metabolic models. I then developed a framework for inferring absolute concentrations from relative abundances in metabolomics data, which will allow metabolomics (the systems-scale study of metabolites) to be more easily used with metabolic modeling tools. Finally, I implemented new constraints within a linear programming dynamic modeling framework that increase its ability to model a wider variety of metabolic systems. Together, these three platforms create a cohesive workflow for modeling the dynamics of metabolism at any scale.

]]> Laura Paige 1 1620831264 2021-05-12 14:54:24 1620831264 2021-05-12 14:54:24 0 0 event BioE PhD Defense Presentation- "Computational modeling of metabolic pathways toward predicting dynamic phenotypes" - Justin Lee

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2021-05-24T11:00:00-04:00 2021-05-24T13:00:00-04:00 2021-05-24T13:00:00-04:00 2021-05-24 15:00:00 2021-05-24 17:00:00 2021-05-24 17:00:00 2021-05-24T11:00:00-04:00 2021-05-24T13:00:00-04:00 America/New_York America/New_York datetime 2021-05-24 11:00:00 2021-05-24 01:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Proposal Presentation- Paul Archer]]> 27917 Advisor:  

Susan Thomas, PhD 

 

Committee Members: 

Julie Champion, PhD 

Brandon Dixon, PhD 

Valeria Milam, PhD 

Krishnendu Roy, PhD 

 

Transport mechanism and administration route influences on accumulation and targeted leukocyte access in the healthy and tumor draining LN 

Lymph nodes are tissues that mediate and organize the congregation of immune cells and are important in the priming of the adaptive immune response. This makes them targets of interest for a variety of immunomodulatory treatments, including cancer immunotherapy. However, achieving therapeutic access to the important leukocyte drug delivery targets within the lymph node can be difficult, as transport from the injection site to the lymph node and transport within the lymph node itself both present significant obstacles due to physical and cellular barriers. To aid in its function facilitating favorable and timely immune responses, the lymph node is a highly structured organ, which introduces compartmentalization of leukocyte subsets and size exclusion parameters to the movements of soluble materials within it; however the influences of these transport barriers on drug delivery system access to the cells involved in the adaptive immune response have yet to be systematically characterized. Furthermore, lymph nodes draining from melanoma tumors undergo significant structural remodeling that may influence drug delivery approaches most suitable for cancer immunotherapy targeted to the tumor-draining lymph node. The objectives of this proposal are to provide fundamental insight into the influences of transport mechanism, route of delivery, material properties, and cell-targeting effects on leukocyte access within the healthy and tumor-draining lymph node, which will be systematically tested using a panel of fluorescent tracers of varied size and flexibility, and nanoparticles with cell-targeted monoclonal antibody moieties in preclinical mouse models. It is hypothesized that delivery to lymph node resident leukocytes can be modulated through lymphatic vs blood vasculature routes of delivery, and that these influences will differ in the tumor draining lymph node due to vascularization changes and structural remodeling. Results will inform the development of improved immunomodulatory treatment delivery strategies broadly, and in the specific application of cancer immunotherapy.

]]> Laura Paige 1 1619026767 2021-04-21 17:39:27 1619026767 2021-04-21 17:39:27 0 0 event BioE PhD Proposal Presentation- "Transport mechanism and administration route influences on accumulation and targeted leukocyte access in the healthy and tumor draining LN " Paul Archer

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2021-04-22T14:30:00-04:00 2021-04-22T16:30:00-04:00 2021-04-22T16:30:00-04:00 2021-04-22 18:30:00 2021-04-22 20:30:00 2021-04-22 20:30:00 2021-04-22T14:30:00-04:00 2021-04-22T16:30:00-04:00 America/New_York America/New_York datetime 2021-04-22 02:30:00 2021-04-22 04:30:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Defense Presentation- April Miguez]]> 27917 Advisor: 

Mark P. Styczynski, Ph.D.

School of Chemical & Biomolecular Engineering, Georgia Institute of Technology

  

Committee Members:  

  

Lily S. Cheung, Ph.D.

School of Chemical & Biomolecular Engineering, Georgia Institute of Technology

 

Meleah A. Hickman, Ph.D.

Department of Biology, Emory University

 

Hang Lu, Ph.D.

School of Chemical & Biomolecular Engineering, Georgia Institute of Technology

 

Ronghu Wu, Ph.D.

School of Chemistry & Biochemistry, Georgia Institute of Technology

 

Interfacing systems and synthetic biology for advancements in Bacterial Biosensor engineering

Current detection platforms ranging from clinical diagnostics to environmental pollutant monitoring often require a time-intensive sample analysis process involving expensive equipment and highly-trained staff. This has led to growing demands for faster, less expensive, more user-friendly platforms. Bacteria have the potential to meet these needs, as they can serve as inexpensive, robust biosensors that can be engineered to detect target molecules while providing fast, easily measurable readouts; however, genetic engineering efforts can often incite metabolic changes that limit biosensing performance. Cell-free bacteria-based biosensors, which use a bacterial protein lysate to perform transcription and translation, can avoid many of the challenges of whole-cell biosensor development, but the uncharacterized metabolic activity in cell-free systems creates a new set of obstacles that must be addressed for effective biosensor design. In this work, I use metabolomics (the systems-scale study of small molecule intermediates involved in the chemical reactions within biological systems) to address these key challenges in whole-cell and cell-free systems to improve their development for biosensing applications. For whole-cell systems, I explore the metabolic effects linked to expression and optimization of a well-characterized biosensor reporter system. For cell-free systems, I characterize their endogenous, dynamic metabolic activity and explore the metabolic impacts of various system perturbations. For both platforms, I identify key metabolites that limit the utility of both whole-cell and cell-free systems and present strategies to address some of the limitations in each platform to facilitate improved biosensor engineering and ultimately broaden the reach of whole-cell and cell-free bacteria-based biosensors.

]]> Laura Paige 1 1619010420 2021-04-21 13:07:00 1619010420 2021-04-21 13:07:00 0 0 event BioE PhD Defense Presentation-  "Interfacing systems and synthetic biology for advancements in Bacterial Biosensor engineering" April Miguez

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2021-04-21T11:00:00-04:00 2021-04-21T13:00:00-04:00 2021-04-21T13:00:00-04:00 2021-04-21 15:00:00 2021-04-21 17:00:00 2021-04-21 17:00:00 2021-04-21T11:00:00-04:00 2021-04-21T13:00:00-04:00 America/New_York America/New_York datetime 2021-04-21 11:00:00 2021-04-21 01:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Proposal Presentation- Maggie Manspeaker]]> 27917 Advisor: 

Susan N. Thomas, Ph.D.

George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology

  

Committee Members:  

  

John Blazeck, Ph.D.

School of Chemical & Biomolecular Engineering, Georgia Institute of Technology

 

Julie Champion, Ph.D.

School of Chemical & Biomolecular Engineering, Georgia Institute of Technology

 

M.G. Finn , Ph.D.

School of Chemistry and Biochemistry, Georgia Institute of Technology

 

Haydn T. Kissick, Ph.D.

Department of Urology, Department of Microbiology and Immunology, Emory University School of Medicine

 

Engineered Nanotechnology for the Delivery of Cancer Immunotherapies to Lymph Nodes to Modulate Anti-Tumor T Cell Immunity

The advent of immunotherapies, particularly immune checkpoint blockade (ICB) monoclonal antibodies (mAbs), to treat advanced cancers has drastically improved outcomes for some patients. These ICB mAbs work by blocking inhibitory immune checkpoint pathways and more recently have been shown to cause a proliferative burst of effector T cells attributable to a subset of antigen-specific CD8 T cells with stem cell-like properties, which are thought to reside in lymphoid tissues and in particular tumor–draining lymph nodes (TdLNs). TdLNs are a critically important tissue that mediates the mounting of effective anti-tumor immunity and are central in the response to ICB immunotherapy both due to active immune checkpoints in TdLNs and their role in housing CD8 stem-like cells. However, despite the promising clinical advances ICB mAbs represent, some patients experience no clinical benefit from therapy, leading to an increase in clinical investigations into various combination therapies that enhance patient response, such as adjuvants and chemotherapies. Additionally, success of cancer therapeutics is often stymied by low accumulation in target tissues and off-target effects. Therefore, a better understanding of how these combination therapies interact with the TdLN and resulting immune response is needed, which can be enabled with the use of nanotechnologies that improve therapeutic efficacy while avoiding success-limiting off-target effects. As such, the overall objective of this project is to use nanotechnologies that enable drug accumulation in the TdLN to 1) investigate how nanotechnology alters the efficacy of combination chemo- and immunotherapy and characterize the involvement of the TdLN in anti-tumor immunity following treatment, and to 2) elucidate the dynamics of CD8 stem-like T cells in response to adjuvant and ICB combination therapy, and characterize the efficacy of engineered drug delivery nanotechnologies on these combinations. This work will provide insight into role of the TdLN, and dynamics of important cell populations within, in the efficacy of drug and ICB combination therapies with clinical relevance and inform promising future therapeutic strategies for cancer.

]]> Laura Paige 1 1618840727 2021-04-19 13:58:47 1618840727 2021-04-19 13:58:47 0 0 event BioE PhD Proposal Presentation- Maggie Manspeaker - "Engineered Nanotechnology for the Delivery of Cancer Immunotherapies to Lymph Nodes to Modulate Anti-Tumor T Cell Immunity"

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2021-04-28T15:00:00-04:00 2021-04-28T17:00:00-04:00 2021-04-28T17:00:00-04:00 2021-04-28 19:00:00 2021-04-28 21:00:00 2021-04-28 21:00:00 2021-04-28T15:00:00-04:00 2021-04-28T17:00:00-04:00 America/New_York America/New_York datetime 2021-04-28 03:00:00 2021-04-28 05:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE MS Thesis Defense - Mythreye Venkatesan ]]> 27917 Advisor:  

Ahmet F. Coskun, PhD (BME, Georgia Tech & Emory University)   

Committee Members:   

Ghassan AlRegib (ECE, Georgia Institute of Technology) 

Hang Lu, PhD (ChBE, Georgia Institute of Technology) 

Melissa L. Kemp, PhD (BME, Georgia Tech & Emory University) 

   

Rapid microfluidic multiplexing of proteins for deciphering spatial organelle networks 

New technologies in the advancing biotechnology and biomedical engineering have shown us that organelles play many roles in human health and disease. Being the building blocks of the smallest unit of life, organelles play an important role in the health and well-beings of humans. Cell diversity not only exists between cell types but also between individual cells, thus it is important to understand the distribution of organelles at single-cell level. Mesenchymal stem cells, being multipotent, have been explored as a therapeutic for treating a variety of diseases. Studying how organelles are arranged in these cells will answer questions about their function and potential. This thesis aims to understand the spatial organization of organelles and the interactions between them in mesenchymal stem cells using multiplexed imaging of proteins. In this work, rapidly run cyclic immunofluorescence staining was performed to decipher the subcellular localization of ten organelle markers in bone marrow and umbilical cord stem cells. An automated microfluidic system was developed that handles the repetitive manual processes of blocking, washing, staining and bleaching the sample on coverslip during each cycle. Spatial correlations, colocalization analysis, heatmaps and network analysis were carried out on the 10-plex data to explore relations between the organelles. In future, this data-driven single-cell approach can enable personalized stem cell therapeutics. 

]]> Laura Paige 1 1617724638 2021-04-06 15:57:18 1617724638 2021-04-06 15:57:18 0 0 event BioE MS Thesis Defense -   " Rapid microfluidic multiplexing of proteins for deciphering spatial organelle networks " - Mythreye Venkatesan 

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2021-04-13T10:00:00-04:00 2021-04-13T12:00:00-04:00 2021-04-13T12:00:00-04:00 2021-04-13 14:00:00 2021-04-13 16:00:00 2021-04-13 16:00:00 2021-04-13T10:00:00-04:00 2021-04-13T12:00:00-04:00 America/New_York America/New_York datetime 2021-04-13 10:00:00 2021-04-13 12:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE MS Thesis Defense - Pallavi Misra]]> 27917 Advisor: 

Manu O. Platt, Ph.D.

Biomedical Engineering, Georgia Institute of Technology and Emory University  

  

Committee Members:  

  

Michael E. Davis, Ph.D.

Biomedical Engineering, Georgia Institute of Technology and Emory University  

 

Shamkant B. Navathe, Ph.D.

College of Computing, Georgia Institute of Technology  

  

Evaluating roles of miRNAs in cardiac fibrosis: a meta-analysis

 

Cardiovascular diseases are the leading cause of mortality globally. Cardiac fibrosis is an essential component of changes that occur in heart’s size, shape, and composition, in response to cardiac disease or cardiac damage.  Exosomes are extracellular vesicles that aid cell-cell communication and carry proteins, metabolites, nucleic acids, etc. miRNAs are small non-coding RNA molecules that can be transported by exosomes and are uniquely capable of facilitating long-term repair by altering the targeted cells’ transcriptome. Prior studies have demonstrated relationships between exosomal miRNA content and fibrosis in the heart.  In this research, self-built scoring models and Partial Least Squares Regression (PLSR) modeling were used to find miRNAs that can downregulate cardiac fibrosis. miR-21, miR-33, miR-125b, miR-155-5p, miR-34a were identified as profibrotic miRNAs and miR-29b, miR-29a, miR-26a, miR-30c, miR-29c were identified as antifibrotic miRNAs.  Few under-studied miRNAs were also identified that might be important regulators of cardiac fibrosis.  Computational models were built to predict the extent of cardiac fibrosis with miRNAs’ fold-changes as inputs. A computational workflow was developed to predict the extent of cardiac fibrosis when exosomes with custom-designed packages of miRNA content will be injected into animal models. This analysis consolidates relationships between selected miRNAs and cardiac fibrosis, and can be used to inform experimental studies of cardiac remodeling.

]]> Laura Paige 1 1617724465 2021-04-06 15:54:25 1617724465 2021-04-06 15:54:25 0 0 event BioE MS Thesis Defense -  "Evaluating roles of miRNAs in cardiac fibrosis: a meta-analysis" -Pallavi Misra

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2021-04-19T10:00:00-04:00 2021-04-19T12:00:00-04:00 2021-04-19T12:00:00-04:00 2021-04-19 14:00:00 2021-04-19 16:00:00 2021-04-19 16:00:00 2021-04-19T10:00:00-04:00 2021-04-19T12:00:00-04:00 America/New_York America/New_York datetime 2021-04-19 10:00:00 2021-04-19 12:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE MS Thesis Defense - Kristy Yun]]> 27917 Advisor: 

Young-Hui Chang, Ph.D. Biological Sciences, Georgia Institute of Technology  

  

Committee Members:  

  

Boris Prilutsky, Ph.D.  

Biological Sciences, Georgia Institute of Technology  

  

Gregory Sawicki, Ph.D.  

ME, Georgia Institute of Technology  

  

  

Less Work After Spaceflight: 

Human Performance Biomechanics Following Adaptation to Simulated Hypogravity

 

In the next decade, humans are planning to return to the Moon and prepare for future explorations to Mars. Despite our intuitive knowledge of gravity, we still do not fully understand how our bodies develop, function, and navigate in hypogravity environments. This study aimed to evaluate the effect of hypogravity on the biomechanical adaptation of targeted countermovement jumping performance. Fifteen participants jumped in and out of simulated hypogravity using a reduced-gravity simulator that provided a constant upward force near the body’s COM, effectively simulating ~0.5g. The jump was divided into two main phases: (i) Lift (from countermovement initiation to take off) and (ii) Land (from touchdown until stabilization of ground reaction forces). Following hypogravity adaptation, there was a meaningful effect in the normalized work of the Lift and a significant decrease in the Land when compared to the baseline pre-adaptation jumps. Further investigation into the additional parts of the Lift and Land revealed meaningful effects in specifically the last part of the Lift and significant changes in the first part of the Land. Observations of normalized COM work revealed distinct control strategies for the Lift and Land phases. The work generated during the first parts of the Lift appears to be dominantly controlled through a reactive control strategy, as it showed no significant after-effects upon return to 1.0g. In contrast, the work generated during the late part of the Lift and absorbed during the early part of the Land was observed to be predominantly under a predictive control strategy, evidenced by the significant decrease in work upon returning to 1.0g. Thus, upon return to a higher gravity level, movements requiring the legs to quickly generate and absorb energy will be most affected by sensorimotor control prediction errors and should be taken into consideration during the post-adaptation re-acclimation process after prolonged exposure to hypogravity.

]]> Laura Paige 1 1617205190 2021-03-31 15:39:50 1617205190 2021-03-31 15:39:50 0 0 event BioE MS Thesis Defense Kristy Yun  - "Less Work After Spaceflight:  Human Performance Biomechanics Following Adaptation to Simulated Hypogravity"

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2021-04-09T17:30:00-04:00 2021-04-09T19:00:00-04:00 2021-04-09T19:00:00-04:00 2021-04-09 21:30:00 2021-04-09 23:00:00 2021-04-09 23:00:00 2021-04-09T17:30:00-04:00 2021-04-09T19:00:00-04:00 America/New_York America/New_York datetime 2021-04-09 05:30:00 2021-04-09 07:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Proposal Presentation- Dan Zhang]]> 27917 Advisor: Melissa L. Kemp, PhD (BME, Georgia Tech & Emory University)

 

Committee Members:

Wilbur A. Lam, MD, PhD (BME/Pediatrics, Georgia Tech & Emory University)

Manu O. Platt, PhD (BME, Georgia Tech & Emory University)

David K. Wood, PhD (BME, University of Minnesota)

Levi B. Wood, PhD (ME, Georgia Tech)

 

 

Informing Precision Medicine Through Data-driven Modeling of Patient-Specific Therapeutic Responses in Microfluidic-based Assays

 

Precision medicine has the potential to improve patient outcomes through customized clinical decisions for many diseases but is reliant on availability of robust biomarkers and assays for biomarker detection that can accurately quantify the disease state. Microfluidic devices are powerful diagnostic and research tools for functional testing of patient samples; these devices are increasingly sophisticated by incorporating physiological features such as the cellular environment, thus better recapitulating in vivo behavior. As these platforms continue to incorporate more features, analysis and interpretation of patterns within these multi-factorial datasets becomes challenging. For example, high-speed imaging technologies allows for the capture of high throughput quantitative data that incorporate dynamic signals and responses within a single experiment. Without interpretable models of these complex datasets, experimental observations are difficult to translate into clinically actionable insights for precision medicine. New statistical and computational methods are needed to extract the maximal amount of information from the analysis of microfluidics-generated data and overcome the challenges of modeling biological data. The overall objective of this thesis is to leverage computational and mathematical approaches to develop robust predictive models of patient sample response to combinatorial therapies assayed in microfluidic devices. I will validate my approach using microfluidics-generated datasets from application to two hematologic diseases: multi-drug resistance profiling in leukemia, and oxygen-dependent rheological biomarkers in sickle cell disease vaso-occlusion. The frameworks developed here will result in models that can extract important features from multi-factorial experiments, optimize discovery of synergistic interactions, and provide personalized recommendations for therapy.

]]> Laura Paige 1 1615297512 2021-03-09 13:45:12 1615297512 2021-03-09 13:45:12 0 0 event BioE PhD Proposal Presentation-  "Informing Precision Medicine Through Data-driven Modeling of Patient-Specific Therapeutic Responses in Microfluidic-based Assays" - Dan Zhang

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2021-03-09T10:00:00-05:00 2021-03-09T12:00:00-05:00 2021-03-09T12:00:00-05:00 2021-03-09 15:00:00 2021-03-09 17:00:00 2021-03-09 17:00:00 2021-03-09T10:00:00-05:00 2021-03-09T12:00:00-05:00 America/New_York America/New_York datetime 2021-03-09 10:00:00 2021-03-09 12:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Proposal Presentation- Venu Ganti]]> 27917 Advisor:
Omer T. Inan, PhD (Georgia Institute of Technology)

 
Committee:
David Frakes, PhD (Georgia Institute of Technology)
Rishikesan Kamaleswaran, PhD (Georgia Institute of Technology)
Jin-Oh Hahn, PhD (University of Maryland, College Park)
Animesh Tandon, MD (University of Texas Southwestern Medical Center)

Enabling Wearable Hemodynamic Monitoring using Multimodal Cardiomechanical Sensing Systems

Biomarkers such as blood pressure and cardiac output are instrumental to understanding the pathogenesis of cardiovascular disease. Unfortunately, the monitoring of these hemodynamic parameters is still tethered to in-clinic measurements or is too unaccommodating and inconvenient for ubiquitous use. This focus of this proposed work is to explore seismocardiogram-based wearable multimodal sensing techniques to enable the use of digital biomarkers—in particular, blood pressure and cardiac output. First, the performance of a multimodal, wrist-worn device capable of obtaining noninvasive pulse transit time measurements is used to estimate blood pressure in an unsupervised, at-home setting. Second, the feasibility of this wrist-worn device is comprehensively evaluated in a diverse and medically underserved population over the course of several perturbations used to modulate blood pressure through different pathways. Finally, as part of the proposed work, the ability of wearable signals acquired from a patch to noninvasively quantify cardiac output in pediatric congenital heart disease patients is examined in a hospital setting. Successful completion of the proposed work will demonstrate that these advancements represent a step towards enabling frequent, reliable, and accurate measurements in ambulatory settings and offer an opportunity to advance health equity.

 

]]> Laura Paige 1 1613932362 2021-02-21 18:32:42 1613932362 2021-02-21 18:32:42 0 0 event BioE PhD Proposal Presentation- "Enabling Wearable Hemodynamic Monitoring using Multimodal Cardiomechanical Sensing Systems" -Venu Ganti

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2021-03-05T15:00:00-05:00 2021-03-05T17:00:00-05:00 2021-03-05T17:00:00-05:00 2021-03-05 20:00:00 2021-03-05 22:00:00 2021-03-05 22:00:00 2021-03-05T15:00:00-05:00 2021-03-05T17:00:00-05:00 America/New_York America/New_York datetime 2021-03-05 03:00:00 2021-03-05 05:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Proposal Presentation- Musa Mahmood]]> 27917 Advisor: 

W. Hong Yeo, Ph.D. ME, Georgia Institute of Technology  

  

Committee Members:  

  

Frank Hammond, Ph.D.  

ME, Georgia Institute of Technology  

  

Minoru Shinohara, Ph.D.  

Biological Sciences, Georgia Institute of Technology  

  

Todd Sulchek, Ph.D.  

ME, Georgia Institute of Technology  

  

Audrey Duarte, Ph.D.  

Psychology, Georgia Institute of Technology 

  

  

Study of soft materials, flexible electronics, and machine learning for fully portable and wireless brain-machine interfaces 

 

Wireless, wearable electroencephalograms and dry non-invasive electrodes can be utilized to allow recording of brain activity on a mobile subject to allow for unrestricted movement. Additionally, multilayer microfabricated flexible circuits, combined with a soft materials platform, provide imperceptible wearable electronics for wireless, portable, long-term recording of brain signals. This proposal focuses on sharing the study outcomes in soft materials, flexible electronics, and machine learning for universal brain-machine interfaces that could offer remedies in communication and movement for these individuals. Integration of materials, mechanics, circuit, and electrode design results in an optimized brain-machine interface allowing for rehabilitation and overall improved quality of life. 

]]> Laura Paige 1 1613061815 2021-02-11 16:43:35 1613061815 2021-02-11 16:43:35 0 0 event BioE PhD Proposal Presentation- "Study of soft materials, flexible electronics, and machine learning for fully portable and wireless brain-machine interfaces " - Musa Mahmood

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2021-02-23T15:00:00-05:00 2021-02-23T17:00:00-05:00 2021-02-23T17:00:00-05:00 2021-02-23 20:00:00 2021-02-23 22:00:00 2021-02-23 22:00:00 2021-02-23T15:00:00-05:00 2021-02-23T17:00:00-05:00 America/New_York America/New_York datetime 2021-02-23 03:00:00 2021-02-23 05:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioEngineering Graduate Committee Meeting]]> 27917 The BioEngineering graduate committee will meet to review/approve program policies, program faculty applications and submitted student petitions.

]]> Laura Paige 1 1611673185 2021-01-26 14:59:45 1611673185 2021-01-26 14:59:45 0 0 event BioEngineering Graduate Committee Meeting

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2021-04-13T14:00:00-04:00 2021-04-13T15:00:00-04:00 2021-04-13T15:00:00-04:00 2021-04-13 18:00:00 2021-04-13 19:00:00 2021-04-13 19:00:00 2021-04-13T14:00:00-04:00 2021-04-13T15:00:00-04:00 America/New_York America/New_York datetime 2021-04-13 02:00:00 2021-04-13 03:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Proposal Presentation- Alyssa Pybus]]> 27917 Advisor:

Levi B. Wood, Ph.D.

ME, Georgia Institute of Technology

 

Committee Members: 

 

Erin M. Buckley, Ph.D. 

BME, Georgia Institute of Technology and Emory University 

 

Michelle C. LaPlaca, Ph.D. 

BME, Georgia Institute of Technology and Emory University 

 

Manu O. Platt, Ph.D. 

BME, Georgia Institute of Technology and Emory University 

 

Srikant Rangaraju, M.D. M.S.

Department of Neurology, Emory University

 

 

 

Systems Analysis of Neuroinflammation in Repetitive Mild Traumatic Brain Injury

 

Repetitive mild traumatic brain injury (rmTBI) has been linked to devastating long-term neurological pathologies including chronic traumatic encephalopathy, which disproportionately affects athletes, military service members, and victims of domestic abuse. Despite the grave public health concern that rmTBI presents, current therapeutic strategies are limited. It is necessary to illuminate the molecular mechanisms underlying neurodegeneration after injury to identify candidate therapies.

 

Neuroinflammation is implicated in severe traumatic brain injury and represents a likely culprit for driving pathology after rmTBI. The objective of this study is to understand the mechanisms driving neuroinflammation after rmTBI. My hypothesis is that neuroinflammation after rmTBI is driven by specific intracellular signaling pathways first activated in neurons, and that these pathways can be inhibited to improve outcome after rmTBI. The proposed work will identify cell type specific acute phospho-protein signaling pathways and cytokines associated with poor cognitive outcome after rmTBI, investigate neuroinflammatory signaling and its relationship to pathological progression after rmTBI in an Alzheimer’s disease mouse model, and determine whether small molecule inhibition of inflammatory signaling pathways can improve outcome after rmTBI. Uncovering signaling mechanisms driving neuroinflammation after rmTBI will identify possible therapeutic targets for pharmaceutical intervention to improve clinical outcomes of patients recovering from brain injury.

]]> Laura Paige 1 1610726146 2021-01-15 15:55:46 1610726146 2021-01-15 15:55:46 0 0 event BioE PhD Proposal Presentation-  "Systems Analysis of Neuroinflammation in Repetitive Mild Traumatic Brain Injury" - Alyssa Pybus

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2021-01-22T13:00:00-05:00 2021-01-22T15:00:00-05:00 2021-01-22T15:00:00-05:00 2021-01-22 18:00:00 2021-01-22 20:00:00 2021-01-22 20:00:00 2021-01-22T13:00:00-05:00 2021-01-22T15:00:00-05:00 America/New_York America/New_York datetime 2021-01-22 01:00:00 2021-01-22 03:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioEngineering Graduate Committee Meeting]]> 27917 The BioEngineering graduate committee will meet to review/approve program policies, program faculty applications and submitted student petitions.

]]> Laura Paige 1 1610039233 2021-01-07 17:07:13 1610039233 2021-01-07 17:07:13 0 0 event BioEngineering Graduate Committee Meeting

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2021-01-14T13:00:00-05:00 2021-01-14T14:00:00-05:00 2021-01-14T14:00:00-05:00 2021-01-14 18:00:00 2021-01-14 19:00:00 2021-01-14 19:00:00 2021-01-14T13:00:00-05:00 2021-01-14T14:00:00-05:00 America/New_York America/New_York datetime 2021-01-14 01:00:00 2021-01-14 02:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Proposal Presentation- Alejandro J. Da Silva Sanchez ]]> 27917 Advisor:

James E. Dahlman, Ph.D. BME, Georgia Institute of Technology and Emory University 

 

Committee Members: 

 

Philip J. Santangelo, Ph.D. 

BME, Georgia Institute of Technology and Emory University 

 

Julie A. Champion, Ph.D. 

ChBE, Georgia Institute of Technology 

 

Mark P. Styczynski, Ph.D. 

ChBE, Georgia Institute of Technology 

 

MG Finn, Ph.D. 

Chemistry and Biochemistry, Georgia Institute of Technology

 

 

 

The impact of the metabolic state of a cell on nucleic acid therapeutics 

 

Nucleic acid therapies have advanced over the last decade with the FDA approval of the first siRNA drug in 2018 and the recent approval of COVID vaccines leveraging mRNA technology. While surface receptors and endocytosis genes have been shown to influence the effectiveness of RNA drug delivery with lipid nanoparticles (LNPs), the effect of the metabolic state of a cell upon therapies seeking to produce or silence proteins remains understudied. This project therefore aims to (i) understand whether metabolic perturbations to the mTOR pathway upon PIP3 extracellular administration affect LNP-mediated mRNA delivery, (ii) develop cell- and mouse-agnostic high throughput LNP screening systems for siRNA and DNA drugs that will allow scientists to perform mechanistic studies on functional delivery with genetic knockout mice, and (iii) leverage these platforms to study whether mice exhibiting different levels of activity across the mTOR signaling pathway are more or less receptive to different nucleic acid drugs. This work will constitute early steps toward two equally important goals: (a) exploiting natural differences in cell signaling to improve cell type–specific nanoparticle delivery and (b) understanding how different physiological states can lead to different delivery potencies of nucleic acid therapeutics. 

]]> Laura Paige 1 1610039101 2021-01-07 17:05:01 1610039101 2021-01-07 17:05:01 0 0 event BioE PhD Proposal Presentation-  "The impact of the metabolic state of a cell on nucleic acid therapeutics " - Alejandro J. Da Silva Sanchez 

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2021-01-19T15:00:00-05:00 2021-01-19T17:00:00-05:00 2021-01-19T17:00:00-05:00 2021-01-19 20:00:00 2021-01-19 22:00:00 2021-01-19 22:00:00 2021-01-19T15:00:00-05:00 2021-01-19T17:00:00-05:00 America/New_York America/New_York datetime 2021-01-19 03:00:00 2021-01-19 05:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Proposal Presentation- Michael Hunckler]]> 27917 Advisor:

Dr. Andrés García (ME, Georgia Institute of Technology)

 

Committee Members:

Dr. Edward Botchwey (BME, Georgia Institute of Technology)

Dr. Krish Roy (BME, Georgia Institute of Technology)

Dr. Ankur Singh (ME, Georgia Institute of Technology)

Dr. M. Cristina Nostro (University of Toronto)

 

Synthetic Hydrogel-mediated Maturation and Engraftment of Human Pluripotent Stem Cell-Derived β-cells

A functional cure for type 1 diabetes (T1D) could be stem-cell derived β-cell replacement to restore the insulin-producing β-cells that were destroyed by autoimmune system. Human pluripotent stem cells (hPSCs) can differentiate into insulin-producing monohormonal cells that phenotypically and functionally resemble immature β-cells. While promising, fully functional in vitro differentiation of these hPSCs into mature β-cells remains elusive. Current in vitro differentiation protocols of hPSCs cannot provide the precise microenvironmental cues necessary for complete maturation. Consequently, in vivo implantation is often used to direct end-stage maturation of stem cells, resulting in an uncontrolled environment to direct β-cell maturation. Furthermore, there are few suitable delivery vehicles for transplantation to clinically-translatable extrahepatic sites. These challenges highlight the need for strategies that enhance the in vitro maturation of the hPSC-derived β-cells and improve their engraftment and function in a clinically-translatable transplant site. The objective of this project is to engineer advanced synthetic hydrogels to direct in vitro maturation and function of hiPSC-derived β-cells and enhance engraftment and vascularization in an extrahepatic murine transplant site. This will be achieved through two specific aims: (1) human induced pluripotent stem cells (hiPSCs) will be encapsulated in engineered synthetic hydrogels that direct the in vitro differentiation to a mature β-cell stage. Encapsulated β-cells will be evaluated for their viability, function, and maturation. (2) Pancreatic progenitors and immature β-cells will be transplanted into the clinically-relevant, extrahepatic gonadal fat pad with synthetic vasculogenic hydrogels to promote β-cell engraftment, maturation, and function. This project will provide a significant foundation for translation of hiPSC-derived β-cells into more clinically-relevant sites and establish innovative materials that promote survival, engraftment, and function of hiPSC-derived β-cells.

 

 

]]> Laura Paige 1 1609786693 2021-01-04 18:58:13 1609786693 2021-01-04 18:58:13 0 0 event BioE PhD Proposal Presentation- "Synthetic Hydrogel-mediated Maturation and Engraftment of Human Pluripotent Stem Cell-Derived β-cells"  -Michael Hunckler

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2021-01-12T12:00:00-05:00 2021-01-12T14:00:00-05:00 2021-01-12T14:00:00-05:00 2021-01-12 17:00:00 2021-01-12 19:00:00 2021-01-12 19:00:00 2021-01-12T12:00:00-05:00 2021-01-12T14:00:00-05:00 America/New_York America/New_York datetime 2021-01-12 12:00:00 2021-01-12 02:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Proposal Presentation- David Ryoo]]> 27917 Advisor:

Dr. James C. Gumbart (Physics, Georgia Institute of Technology)

 

Committee Members:

Dr. Julie Champion (ChBE, Georgia Institute of Technology)

Dr. Thomas DiChristina (Biology, Georgia Institute of Technology)

Dr. Harold Kim (Physics, Georgia Institute of Technology)

Dr. Todd Sulchek (ME, Georgia Institute of Technology)

 

Resolving the secretion pathway of autotransporters using an AT-BAM complex hybrid structure

Many Gram-negative bacteria invade hosts and evade host cell defense systems by using virulence factors. These virulence factors are exported out of the cell via outer membrane proteins called autotransporters. The autotransporters are composed of the virulence-containing N-terminal passenger domain, and C-terminal translocon, which is folded by the beta-barrel assembly machinery (BAM) complex. The BAM complex is composed of five proteins from BamA to BamE. As an essential protein of the complex, BamA plays a key functional role in the folding and insertion of other outer membrane proteins, and it was shown experimentally that BamA may play a role in the passenger domain secretion of the autotransporters. However, no clear explanation behind such processes has been elucidated. In this proposal, I aim to address this problem by 1) resolving insertion and folding intermediates of the autotransporters EspP and YadA, 2) identifying the pathway of passenger domain secretion through BamA-autotransporter hybrid, and 3) determining the individual role of accessory proteins to the dynamics of BamA’s so-called lateral gate. By addressing these aims, I will uncover a mechanistic link connecting folding, insertion, and secretion of the passenger domain of autotransporters via the BAM complex.

]]> Laura Paige 1 1606750633 2020-11-30 15:37:13 1606750633 2020-11-30 15:37:13 0 0 event BioE PhD Proposal Presentation- "Resolving the secretion pathway of autotransporters using an AT-BAM complex hybrid structure" - David Ryoo

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2020-12-08T11:00:00-05:00 2020-12-08T13:00:00-05:00 2020-12-08T13:00:00-05:00 2020-12-08 16:00:00 2020-12-08 18:00:00 2020-12-08 18:00:00 2020-12-08T11:00:00-05:00 2020-12-08T13:00:00-05:00 America/New_York America/New_York datetime 2020-12-08 11:00:00 2020-12-08 01:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Jeffrey Gau]]> 27917 Advisor: 

Dr. Simon Sponberg (Georgia Institute of Technology) 

 

Committee: 

Dr. Saad Bhamla (Georgia Institute of Technology) 

Dr. Nick Gravish (University of California, San Diego) 

Dr. David Hu (Georgia Institute of Technology) 

Dr. Kurt Wiesenfeld (Georgia Institute of Technology) 

 

Beyond resonance: synchronous and stretch-activated actuation in insect flight 

 

The generation of high power, rhythmic movement is a common feature of biological and robotic locomotion. Insects stand out among these systems because wingbeat frequencies are often an order of magnitude greater (up to 1000 Hz) and face the extreme energetic costs of flapping wing flight. Given the oscillatory nature of insect flight, insects are believed to be resonant. In this framework, elastic structures significantly reduce inertial power costs by storing and returning excess kinetic energy during a wing stroke. However, evidence suggests that a resonance model of flight is incomplete. Unlike the time-periodic (e.g. sinusoidal) forcing of resonant systems, many insects have evolved strain-dependent muscles. Pairs of these muscles excite each other independently from neural input.  

 

This thesis explores how strain-dependent actuators coupled to deformable systems generate high power, rhythmic movements. In Chapter 1, we identified how spring-like properties emerge from heterogeneous exoskeletal shell. Notably, the exoskeleton alone satisfies the energy exchange demands of flight. In Chapter 2, we perturbed hawkmoths and discovered the capacity for +/- 16% frequency modulation at the wingstroke timescale. Unlike their robotic counterparts that explicitly abdicate frequency modulation in favor of energy efficiency, frequency modulation is an underappreciated control strategy in insect flight. In Chapter 3, we developed a mechanical model of hawkmoth mechanics and found that wingbeat frequencies are 50% above resonance. These results suggest that resonance tuning is neither a ubiquitous nor necessary feature of insect flight. Finally, in Chapter 4, we introduced both time periodic and stretch activated forcing to the passive mechanical system. We discovered that a small set of parameters drive transitions between synchronous and self-excited wingbeats. This single dynamical system explains evolutionary transitions in insects and generalizes to robotic systems. 

 

]]> Laura Paige 1 1606750369 2020-11-30 15:32:49 1606750369 2020-11-30 15:32:49 0 0 event BioE PhD Defense Presentation-  "Beyond resonance: synchronous and stretch-activated actuation in insect flight " - Jeffrey Gau

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2020-12-09T12:00:00-05:00 2020-12-09T14:00:00-05:00 2020-12-09T14:00:00-05:00 2020-12-09 17:00:00 2020-12-09 19:00:00 2020-12-09 19:00:00 2020-12-09T12:00:00-05:00 2020-12-09T14:00:00-05:00 America/New_York America/New_York datetime 2020-12-09 12:00:00 2020-12-09 02:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Angel J. Santiago-Lopez ]]> 27917 Advisor: 

Robert Gross, MD, PhD (Emory University) 

 

Committee: 

Michelle LaPlaca, PhD (Georgia Institute of Technology) 

Mark Prausnitz, PhD (Georgia Institute of Technology) 

Ravi Kane, PhD (Georgia Institute of Technology) 

Jae-Kyung (Jamise) Lee, PhD (University of Georgia) 

 

 

Development and Characterization of Viral Vectors for Stress-Dependent Transgene Expression in Neurons 

The overarching goal of this work was to design and characterize expression vectors that were responsive to physiological changes associated with neurodegenerative disease. The development of this molecular tool responds to the need for physiologically responsive constructs designed to prevent unwanted side effects related to transgene overexpression in current gene therapy interventions. To accomplish this, we adopted regulatory elements from the unfolded protein response (UPR), a homeostatic mechanism used by cells to cope with stress. Thus, by harnessing a biological signal associated with how cells respond to stress conditions, we created stress-responsive viral vectors and demonstrated their use in neurons. This thesis describes the characterization of these vectors by extensive time-lapse fluorescent microscopy assays in several in vitro models of proteostasis dysfunction, including er stress, proteasome inactivation, phosphatase inhibition, and alpha-synuclein overexpression. Collectively, our results demonstrate the feasibility of mobilizing cellular stress signaling to create physiologically-responsive viral vectors for use in neuroscience.  

]]> Laura Paige 1 1606750028 2020-11-30 15:27:08 1606750028 2020-11-30 15:27:08 0 0 event BioE PhD Defense Presentation-  "Development and Characterization of Viral Vectors for Stress-Dependent Transgene Expression in Neurons " - Angel J. Santiago-Lopez 

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2020-12-11T15:00:00-05:00 2020-12-11T17:00:00-05:00 2020-12-11T17:00:00-05:00 2020-12-11 20:00:00 2020-12-11 22:00:00 2020-12-11 22:00:00 2020-12-11T15:00:00-05:00 2020-12-11T17:00:00-05:00 America/New_York America/New_York datetime 2020-12-11 03:00:00 2020-12-11 05:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Proposal Presentation- Ashkan Ojaghi]]> 27917 Advisor:

Dr. Francisco E. Robles (BME, Georgia Institute of Technology)

 

Committee Members:

Dr. Wilbur Lam (BME, Georgia Institute of Technology)

Dr. David Myers (BME, Georgia Institute of Technology)

Dr. Marcus Cicerone (Chemistry and Biochemistry, Georgia Institute of Technology)

Dr. Shu Jia (BME, Georgia Institute of Technology)

 

Deep-Ultraviolet Microscopy and Spectroscopy of Biological Samples

Ultraviolet (UV) spectroscopy is a powerful tool for quantitative analysis of biochemicals, however its application to molecular imaging and microscopy has been limited. The use of deep-ultraviolet (e.g., 220-450 nm) light for microscopy offers many potential advantages over traditional methods, including higher spatial resolution due to the light’s shorter wavelength; and, when combined with spectroscopy, quantitative information with access to many endogenous molecules that play an important role in cell and tissue function and structure. In this work, we first demonstrate the unique capabilities of deep-UV microscopy and spectroscopy in characterization of biomolecules within live cells by extracting their optical attenuation and dispersion spectra. We then extend our measurements to several important biochemicals and established a database for optical properties of these biomolecules in the deep-UV region. By leveraging the biochemical specificity of UV spectroscopy for molecular imaging, we developed a novel label-free assay based on multi-spectral deep-UV microscopy by which we explored different clinical applications such as hematology analysis as well as cellular phenotyping through imaging of blood and bone marrow smears as well as cultured cells. The results of this work can pave the way for development of label-free diagnostic systems for use in clinical and point-of-care settings.

]]> Laura Paige 1 1604353502 2020-11-02 21:45:02 1604353502 2020-11-02 21:45:02 0 0 event BioE PhD Proposal Presentation-  "Deep-Ultraviolet Microscopy and Spectroscopy of Biological Samples" - Ashkan Ojaghi

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2020-11-10T12:00:00-05:00 2020-11-10T14:00:00-05:00 2020-11-10T14:00:00-05:00 2020-11-10 17:00:00 2020-11-10 19:00:00 2020-11-10 19:00:00 2020-11-10T12:00:00-05:00 2020-11-10T14:00:00-05:00 America/New_York America/New_York datetime 2020-11-10 12:00:00 2020-11-10 02:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Jacob Misch]]> 27917 Committee:       Dr. Stephen Sprigle, Advisor (ME, ID, Georgia Institute of Technology)
Dr. Aldo Ferri (ME, Georgia Institute of Technology)
Dr. Frank Hammond (BME, Georgia Institute of Technology)
Ramakant Rambhatla, MBA (Invacare Corp.)
Dr. Sharon Sonenblum (ME, Georgia Institute of Technology)

 

Mechanical Performance Characterization of Manual Wheelchairs Using Robotic Wheelchair Operator with Intermittent Torque-Based Propulsion

 

The current manual wheelchair design process lacks consistent and objective connection to performance-based metrics. The goal of this research was to empirically assess over-ground manual wheelchair performances and identify important design trade-offs through the use of a robotic apparatus with a novel cyclic propulsion control method. This research had four specific aims: 1) to design, implement, and validate torque-based propulsion to emulate the intermittent human propulsion cycle with an existing robotic wheelchair tester, 2) to investigate the influence of incremental mass additions to the wheelchair frame on over-ground propulsion characteristics, 3) to demonstrably improve the performance of a representative high-strength lightweight wheelchair by leveraging existing component-level test results, and 4) to characterize the mechanical performances of representative folding and rigid ultra-lightweight wheelchair frames. The outcomes of this research include an objective, repeatable, and validated test method to assess over-ground performances of manual wheelchairs in realistic contexts of use, as well as insight on the mechanics of the system that were previously under-studied or confounded by variabilities within human subject testing. Controlled propulsion tests are used to identify differences between wheelchair configurations. The outcome variable of propulsion cost represents the energetic requirements of propelling each chair a given distance and has direct relevance to manufacturers, clinicians, and wheelchair users alike. Ultimately, these outcomes will inform clinicians and manufacturers about how configuration choices influence propulsive efforts, which can be used in turn to improve their classification techniques and existing design processes. This knowledge will additionally empower wheelchair users to make informed choices during the wheelchair selection process based on objective mechanical performance metrics.

]]> Laura Paige 1 1603987419 2020-10-29 16:03:39 1603987419 2020-10-29 16:03:39 0 0 event BioE PhD Defense Presentation- "Mechanical Performance Characterization of Manual Wheelchairs Using Robotic Wheelchair Operator with Intermittent Torque-Based Propulsion "- Jacob Misch

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2020-11-12T14:00:00-05:00 2020-11-12T16:00:00-05:00 2020-11-12T16:00:00-05:00 2020-11-12 19:00:00 2020-11-12 21:00:00 2020-11-12 21:00:00 2020-11-12T14:00:00-05:00 2020-11-12T16:00:00-05:00 America/New_York America/New_York datetime 2020-11-12 02:00:00 2020-11-12 04:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Zhou Yuan]]> 27917 Advisor:

Dr. Cheng Zhu (Georgia Institute of Technology)

 

Committee:

Dr. Susan Thomas (Georgia Institute of Technology)

Dr. Michelle Krogsgaard (New York University)

Dr. Mandy Ford (Emory University)

Dr. Gabe Kwong (Georgia Institute of Technology)

 

Regulation of T-cell antigen recognition by melanoma tumor microenvironment and TCR-CD3 ectodomain interaction

 

Despite the critical role of CD8+ T cells in tumor clearance, their functions are impaired by immunosuppressive cells/cytokines, through inhibitory receptors, and metabolic restrictions in the tumor microenvironment (TME). Targeting these suppressive pathways were shown to promote tumor clearance, yet unknown mechanisms may still exist curtailing the T cell responses. The T cell activation and anti-tumor response are initiated by the T cells receptor (TCR) recognizing antigen peptide presented by major histocompatibility complex (pMHC) molecules on antigen presenting cells (APC). Recent studies have demonstrated that comparing to in solution (or three-dimensional, 3D) kinetic measurements that uses purified TCR molecules, analysis of pMHC interacting with TCRs expressed on native T cells (or two-dimensional, 2D) provides a better prediction of T cell function and is able to capture perturbations of antigen recognition by T cell intrinsic and extrinsic mechanisms. In this study, we examined whether T cell antigen recognition is altered by the TME, and thus contributes to the T cell dysfunction. By testing the OT-I T cells from the murine B16F10 melanoma TME with their cognate antigen pMHC OVA:H2Kb, we showed that the TCR-pMHC 2D affinity is reduced in TME. The presence of tumor modulated TCR mechanosensing of antigen pMHC, converting a typical TCR-pMHC catch bond into slip bonds. The T cells from TME gave a reduced spreading on pMHC coated surface, with a decreased TCR-pMHC tension signal generated by spontaneous T cell pulling on pMHC at force over 4.7pN. The TME altered dynamic response of T cell CD3ζ phosphorylation, and reduced level of calcium flux following in vitro stimulations. Using T cell in vitro activation, in vivo proliferation and ex vivo cytokine production as readouts, we showed that removing the TME restores T cell function that was impaired by this antigen inexperienced mechanism. Further analysis showed that nitration of TCR, which can be caused by presence of MDSCs in TME and induces T cell tolerance induced dysfunction, reduced TCR-pMHC 2D affinity. Presence of immunosuppressive Treg and cytokine TGF-β in TME is known to impair CD8+ T cell activation and function. We showed that in vivo TGF-β inhibition and CD4 depletion in tumor bearing animal partially restored the TME altered TCR-pMHC interaction. To summarize, we found that the impaired TCR-pMHC mechanosensing correlated with a reduced T cell function in TME, while this tumor antigen inexperienced suppression was functionally reversible. We also identified several immunosuppressive factors as the potential mechanisms of TME impairment on T cell antigen recognition.

 

TCR α chain and β chain bind noncovalently to dimeric subunits CD3δε, CD3γε, and CD3ζζ to form TCR complex. Upon TCRαβ engaging the antigen pMHC, this binding signal is transmitted through TCR-CD3 interaction, phosphorylates the immunoreceptor tyrosine-based activation motifs (ITAMs) on CD3 cytoplamic tails, which triggers the T cell activation. The interactions among TCR, CD3δε and CD3γε ectodomains are weak in 2D affinities, with short-moderate duration of averaged lifetimes, however disrupting these interactions affects TCR complex stability, signaling and significantly reduces T cell function. In this study, we examed how this weak TCR-CD3 extracellular interaction severely impacts T cell function and whether this impact is through regulating T cell antigen recongition. We found that purified TCR proteins bind to a mixture of CD3δε and CD3γε ectodomain proteins at an increased likelihood and increased average lifetime, comparing to TCR-CD3δε or TCR-CD3γε interaction. This proved the existence of cooperativity among TCR-CD3 extracellular domain interactions. The antibody/Fab targeting TCR and CD3 ectodomains can block TCR-CD3 extracellular interaction and reduce T cell functional response. We showed that the TCR-CD3 interaction blocking Fab treatments decreased TCR-pMHC 2D affinity and altered TCR-pMHC interaction force response profile. Together, these results indicate that TCR-CD3 extracellular interactions is enhanced by the cooperativity among the ectodomain interactions, and regulates T cell function through altering TCR mechanosensing.

 

In this study, we identified impaired T cell antigen recognition as one mechanism of T cell dysfunction in TME. We also identified the cooperativity enhanced TCR-CD3 extracellular interaction as a regulating factor of T cell function by affecting T cell antigen recognition. The results greatly extend our understanding on how the T cell antigen recognition is regulated in physiological and pathological conditions, providing the molecular basis for developing pharmacological approaches to restore/promote or suppress T cell response by regulating T cell antigen recognition.

]]> Laura Paige 1 1603115687 2020-10-19 13:54:47 1603115687 2020-10-19 13:54:47 0 0 event BioE PhD Defense Presentation-  "Regulation of T-cell antigen recognition by melanoma tumor microenvironment and TCR-CD3 ectodomain interaction"- Zhou Yuan

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2020-10-29T10:30:00-04:00 2020-10-29T12:30:00-04:00 2020-10-29T12:30:00-04:00 2020-10-29 14:30:00 2020-10-29 16:30:00 2020-10-29 16:30:00 2020-10-29T10:30:00-04:00 2020-10-29T12:30:00-04:00 America/New_York America/New_York datetime 2020-10-29 10:30:00 2020-10-29 12:30:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Anish Mukherjee]]> 27917 Advisor: Dr. J. Brandon Dixon

 

Committee Members:

Dr. Levi Wood (Georgia Institute of Technology)

Dr. Hanjoong Jo (Georgia Institute of Technology)

Dr. Stanislav Emelianov (Georgia Institute of Technology)

Dr. Michael J. Davis (University of Missouri)

 

Optimum Mechanomodulation of Lymphatic Vessel Contractility Using Oscillatory Pressure Waveforms

The lymphatic system is a network of vessels and nodes transporting and clearing interstitial fluid, orchestrating the immune response, and facilitating lipid transport. An important component of the lymphatic system are the collecting lymphatic vessels which pump lymph through the body by virtue of their intrinsic contractility. The collecting lymphatic vessels are known to be sensitive to their mechanical microenvironment which dictates their contractility. However, relatively little is known about how collecting lymphatic vessel contractility is modulated by their oscillatory mechanical microenvironment and how this mechanosensitivity is affected by lymphatic injury. It is important to know the limits of the mechanomodulation of lymphatic vessels in both physiological and pathological circumstances, since an aberrant microenvironment is frequently associated with lymphatic dysfunction, such as in the case of lymphedema. The present work investigates the role of the oscillatory microenvironment in lymphatics for modulating collecting lymphatic contractility. The mechanomodulation of isolated collecting lymphatic vessels by oscillatory shear stress was investigated and optimal parameters of stimulation were identified for maximizing lymphatic function. The modulation of lymphatic vessels was also investigated in vivo in response to oscillatory pressure gradients mimicking pressure waveforms during massage. Massage-like waveforms modulated collecting lymphatic vessel contractility, and this modulation was altered by lymphatic injury. Thus the oscillatory microenvironment is shown to be an important regulator of lymphatic contractility and the present work provides clues on how the mechanosensitivity of lymphatics can be harnessed to better understand therapeutic approaches to lymphedema.

]]> Laura Paige 1 1602520405 2020-10-12 16:33:25 1602520405 2020-10-12 16:33:25 0 0 event BioE PhD Defense Presentation- "Optimum Mechanomodulation of Lymphatic Vessel Contractility Using Oscillatory Pressure Waveforms" - Anish Mukherjee

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2020-10-23T14:00:00-04:00 2020-10-23T16:00:00-04:00 2020-10-23T16:00:00-04:00 2020-10-23 18:00:00 2020-10-23 20:00:00 2020-10-23 20:00:00 2020-10-23T14:00:00-04:00 2020-10-23T16:00:00-04:00 America/New_York America/New_York datetime 2020-10-23 02:00:00 2020-10-23 04:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Defense Presentation- Laura Weinstock]]> 27917 Advisor: Levi Wood

 

Committee Members:

Dr. Alicia Lyle (CDC)

Dr. Melissa Kemp (Georgia Institute of Technology)

Dr. Manu Platt (Georgia Institute of Technology)

Dr. Srikant Rangaraju (Emory University)

Dr. Krishnendu Roy (Georgia Institute of Technology)

 

Temporal Regulation of Pro-Inflammatory Macrophage and Microglia Activation Dynamics Using Model Predictive Control

Today, chronic inflammatory diseases, including neurodegenerative conditions, cancer, and heart disease, account for more than 50% of deaths globally. There is thus an urgent need for novel strategies to treat such diseases. Alzheimer’s disease (AD) is an example of one such disease that presents both a significant challenge and urgent unmet need because there are no clinically approved treatments to stop or slow disease progression. Years of dysfunctional immune activity during the early stages of AD can create damaging cycles of inflammatory dysregulation and pathology accumulation. However, suppression of neural immune activity has not proven to be an effective strategy for AD treatment, perhaps in part because healthy immune function is increasingly recognized to involve a temporally dynamic process. Thus, a new method is needed to exert temporal control over dysregulated immune activity in AD and other currently intractable diseases. A computational model that captures dynamic immune activity could be used to predict and control the immune response under pathological conditions to recover the immune functionality of healthy tissues. In this thesis, I hypothesized that the application of engineering control theory tools could both quantitatively model immune system responses in disease environments and predict the temporal input trajectory, e.g. treatment regimen, needed to maintain a desired reference level of activity. Indeed, system models were identified that predicted stimuli sequences needed to sustain inflammatory activity and increase pathology clearance, which are lost in chronic disease. I demonstrated the controllability of macrophage pro-inflammatory activity and microglial uptake of the hallmark protein of AD, Aβ, in vitro. The results of these in vitro studies informed a temporal immunomodulation treatment strategy that I administered in vivo in a mouse model of AD. Preliminary in vivo results showed a recovery of homeostatic immune activity and reduced AD pathology. Future work will apply the model frameworks in vivo, further establishing dynamic, model-predicted immune modulation as a novel treatment strategy for AD and beyond. 

]]> Laura Paige 1 1600961750 2020-09-24 15:35:50 1600961750 2020-09-24 15:35:50 0 0 event BioE PhD Defense Presentation- "Temporal Regulation of Pro-Inflammatory Macrophage and Microglia Activation Dynamics Using Model Predictive Control" - Laura Weinstock

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2020-10-06T12:00:00-04:00 2020-10-06T14:00:00-04:00 2020-10-06T14:00:00-04:00 2020-10-06 16:00:00 2020-10-06 18:00:00 2020-10-06 18:00:00 2020-10-06T12:00:00-04:00 2020-10-06T14:00:00-04:00 America/New_York America/New_York datetime 2020-10-06 12:00:00 2020-10-06 02:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE Faculty Meeting]]> 27917 The BioEngineering Program faculty meet regularly during the semester to address program policies, events and future research and academic directions.

]]> Laura Paige 1 1599139604 2020-09-03 13:26:44 1599139604 2020-09-03 13:26:44 0 0 event BioE Faculty Meeting

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2020-10-01T12:00:00-04:00 2020-10-01T13:00:00-04:00 2020-10-01T13:00:00-04:00 2020-10-01 16:00:00 2020-10-01 17:00:00 2020-10-01 17:00:00 2020-10-01T12:00:00-04:00 2020-10-01T13:00:00-04:00 America/New_York America/New_York datetime 2020-10-01 12:00:00 2020-10-01 01:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Timothy Sowers]]> 27917 Advisor: Stanislav Emelianov

 

Committee Members:

Dr. Levent Degertekin (Georgia Institute of Technology)

Dr. David Ku (Georgia Institute of Technology)

Dr. Brooks Lindsey (Georgia Institute of Technology)

Dr. Muralidhar Padala (Emory University)

 

Advancing Photoacoustic Imaging as a Tool for Disease Diagnosis

 

                Photoacoustics is an imaging modality that uses short pulses of laser light to probe tissue for physical properties that have diagnostic value.  Applications have been developed widely, including for improved diagnostic of primary and metastatic tumors, atherosclerosis, and arthritis.  In this dissertation, photoacoustic imaging as a diagnostic tool is advanced in two ways.  Methods for improving light penetration and determining light distribution are improved.  A set of simulations of light propagation is used to optimize the geometry of photoacoustic imaging setups for light penetration.  Optimal geometries are suggested for researchers depending on the tissue type, wavelength, and imaging species of their application.  It was found that several times more light will be delivered in mice than humans, which has implications for the clinical translation of imaging techniques developed in mice across the field of photoacoustics.  Next, a new technique is introduced that could be used to compensate for the decrease in fluence deep in tissue.  A set of simulations are used to show the viability of the technique, and to show its effectiveness in a simulated phantom.  The safety of intravascular photoacoustics is also investigated.  Intravascular photoacoustics is a catheter-based imaging modality meant to improve identification of atherosclerotic plaques.  A set of in vitro experiments indicated that the light dosage damage threshold may be low enough to limit the imaging protocols that can be used safely.  Next, experiments were conducted in vivo to test for damage to the wall of the carotid artery in swine at multiple clinically relevant dosages.  Damage was found at the highest dosages.  However, no vessel wall damage was found at dosages that have been used successfully to image plaque in recent in vivo studies.  This indicates that intravascular photoacoustic imaging can be used to identify lipid plaque without damaging the artery wall, although future studies to corroborate this result are needed.  

 

]]> Laura Paige 1 1599139423 2020-09-03 13:23:43 1599139423 2020-09-03 13:23:43 0 0 event BioE PhD Defense Presentation- "Advancing Photoacoustic Imaging as a Tool for Disease Diagnosis"- Timothy Sowers

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2020-09-16T14:00:00-04:00 2020-09-16T16:00:00-04:00 2020-09-16T16:00:00-04:00 2020-09-16 18:00:00 2020-09-16 20:00:00 2020-09-16 20:00:00 2020-09-16T14:00:00-04:00 2020-09-16T16:00:00-04:00 America/New_York America/New_York datetime 2020-09-16 02:00:00 2020-09-16 04:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioEngineering Graduate Committee Meeting]]> 27917 The BioEngineering graduate committee will meet to review/approve program policies, program faculty applications and submitted student petitions.

]]> Laura Paige 1 1598462181 2020-08-26 17:16:21 1598462181 2020-08-26 17:16:21 0 0 event BioEngineering Graduate Committee Meeting

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2020-11-20T12:00:00-05:00 2020-11-20T13:00:00-05:00 2020-11-20T13:00:00-05:00 2020-11-20 17:00:00 2020-11-20 18:00:00 2020-11-20 18:00:00 2020-11-20T12:00:00-05:00 2020-11-20T13:00:00-05:00 America/New_York America/New_York datetime 2020-11-20 12:00:00 2020-11-20 01:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioEngineering Graduate Committee Meeting]]> 27917 The BioEngineering graduate committee will meet to review/approve program policies, program faculty applications and submitted student petitions.

]]> Laura Paige 1 1598462102 2020-08-26 17:15:02 1598462102 2020-08-26 17:15:02 0 0 event BioEngineering Graduate Committee Meeting

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2020-10-23T11:00:00-04:00 2020-10-23T12:00:00-04:00 2020-10-23T12:00:00-04:00 2020-10-23 15:00:00 2020-10-23 16:00:00 2020-10-23 16:00:00 2020-10-23T11:00:00-04:00 2020-10-23T12:00:00-04:00 America/New_York America/New_York datetime 2020-10-23 11:00:00 2020-10-23 12:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioEngineering Graduate Committee Meeting]]> 27917 The BioEngineering graduate committee will meet to review/approve program policies, program faculty applications and submitted student petitions.

]]> Laura Paige 1 1598461958 2020-08-26 17:12:38 1598461958 2020-08-26 17:12:38 0 0 event BioEngineering Graduate Committee Meeting

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2020-09-25T14:00:00-04:00 2020-09-25T15:00:00-04:00 2020-09-25T15:00:00-04:00 2020-09-25 18:00:00 2020-09-25 19:00:00 2020-09-25 19:00:00 2020-09-25T14:00:00-04:00 2020-09-25T15:00:00-04:00 America/New_York America/New_York datetime 2020-09-25 02:00:00 2020-09-25 03:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE MS Thesis Presentation - Yanina Kuzminich]]> 27917 Advisor:

J. Brandon Dixon, PhD (Georgia Institute of Technology)

 

Committee:

Erin Buckley, PhD (Emory University/Georgia Institute of Technology)

Rudolph Gleason, PhD (Georgia Institute of Technology)

 

 

Non-Invasive Imaging of Lymphatic Remodeling In Response To Injury Through Photodynamic Therapy

 

The lymphatic system is an essential but often understudied in comparison with its cardiovascular counterpart. Such disparity could often be explained by the lack or complexity of the existing imaging and analysis techniques available for the quantification of lymphatics compared to the ones available for the blood vasculature. An additional challenge is the absence of representative in vivo models that efficiently replicate the lymphatic dysfunction observed in humans. Those factors result in the continuous investigation of novel models for lymphatic diseases and ways to evaluate the overall function of the lymphatic system. Recently, it has been shown that verteporfin, a photosensitive drug widely used for photodynamic therapy (PDT) to ablate the blood vessels, provides a similar effect on lymphatic vessels. Here, we seek to administer verteporfin and perform PDT in the mouse tail, which is a commonly used location for the study of lymphatic disorders and examine lymphatic remodeling, contractility, and transport in response to the procedure. To quantify the induced changes, the lymphatic function has been evaluated using a near-infrared (NIR) imaging system. Additional image processing has been introduced to access the NIR tracer distribution following the lymphatic injury caused by the verteporfin administration. As a result, we are able to increase lymphatic permeability noninvasively at the targeted area. This technique has the potential to be a stand-alone procedure to investigate the lymphatic response to a localized leakage and ROS environment and serve as an improvement to existing in vivo models of lymphatic disorders.

]]> Laura Paige 1 1595947152 2020-07-28 14:39:12 1595947152 2020-07-28 14:39:12 0 0 event BioE MS Thesis Presentation - "Non-Invasive Imaging of Lymphatic Remodeling In Response To Injury Through Photodynamic Therapy" - Yanina Kuzminich

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2020-08-07T12:00:00-04:00 2020-08-07T14:00:00-04:00 2020-08-07T14:00:00-04:00 2020-08-07 16:00:00 2020-08-07 18:00:00 2020-08-07 18:00:00 2020-08-07T12:00:00-04:00 2020-08-07T14:00:00-04:00 America/New_York America/New_York datetime 2020-08-07 12:00:00 2020-08-07 02:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Nicholas Beskid]]> 27917 Advisor: Julie E. Babensee, PhD (Georgia Institute of Technology)

 

Committee:

Andrés J. García, PhD, (Georgia Institute of Technology)

Susan Thomas, PhD (Georgia Institute of Technology)

Edward Botchwey, PhD (Georgia Institute of Technology)

Jacob Kohlmeier, PhD (Emory University)

 

Functionalized PEG-4MAL Hydrogels for Delivery of Dendritic Cells in Tolerogenic Applications

 

Traditional pharmaceutical and biological treatments suffer from shortcomings in the treatment of autoimmune diseases such as Multiple Sclerosis (MS) due to being non-specific, systemic, and causing serious side effects such as complete immunosuppression and increased risk of other pathologies. Recently, the use of dendritic cells (DCs) as a cell therapy to treat autoimmunity has been investigated, but inadequate delivery to the target site and cell activation due to widespread inflammation has limited their efficacy. To overcome these limitations, biophysical and biochemical cell-biomaterial interactions between DCs and 4-arm maleimide functionalized poly(ethylene glycol) (PEG-4MAL) hydrogels were characterized and hydrogels were optimized to support viability and immaturity in encapsulated DCs. PEG-4MAL hydrogels were subsequently functionalized with modified IL-10, which resulted in prolonged support and protection against inflammation. In a murine model of MS, prophylactic treatment with DCs delayed the onset of symptoms in mice, regardless of delivery method. However, hydrogel-delivered DCs significantly ameliorated symptoms of paralysis compared to therapeutic DCs injected subcutaneously, indicating a more durable tolerogenic response. Post-processing of murine tissues and in vitro co-culture studies showed marked infiltration of endogenous lymphocytes into the immunosuppressive biomaterial niche, where DCs tolerize host cells through induction of CD25+FoxP3+ T regulatory cells (Tregs) and exhaustion of CD8+ T cells mediated by programmed cell death protein 1 (PD-1). A significant reduction of maturation markers amongst CD11b+ APCs in the CNS illustrates that the immunomodulatory effects of this treatment reach the anatomical site of injury. Overall, these results suggest that the tolerogenic biomaterial delivery system developed herein significantly improves the robustness of a DC therapy in a mouse model of MS. Additionally, the DC-biomaterial interactions characterized herein accentuate the flexibility in tuning PEG-4MAL hydrogels for other tolerogenic applications.

 

]]> Laura Paige 1 1594393853 2020-07-10 15:10:53 1594393853 2020-07-10 15:10:53 0 0 event BioE PhD Defense Presentation-  "Functionalized PEG-4MAL Hydrogels for Delivery of Dendritic Cells in Tolerogenic Applications" - Nicholas Beskid

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2020-07-23T12:00:00-04:00 2020-07-23T14:00:00-04:00 2020-07-23T14:00:00-04:00 2020-07-23 16:00:00 2020-07-23 18:00:00 2020-07-23 18:00:00 2020-07-23T12:00:00-04:00 2020-07-23T14:00:00-04:00 America/New_York America/New_York datetime 2020-07-23 12:00:00 2020-07-23 02:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Lina María Mancipe Castro]]> 27917 Advisor: Andrés J. García, PhD, (Georgia Institute of Technology)

Co-advisor: Robert E. Guldberg, PhD (University of Oregon)

 

Committee:

Nick Willett, PhD; (Emory Department of Orthopedics)

SusanThomas, PhD; (Georgia Institute of Technology)

James Dahlman, PhD. (Georgia Institute of Technology)

 

Articular cartilage- and synoviocyte-binding small molecule drug delivery system for the intra-articular treatment of osteoarthritis

 

Intra-articular (IA) injection is an attractive route of administration for the treatment of osteoarthritis (OA). However, free drugs injected into the joint space are subjected to clearance mechanisms, which reduce their IA retention time. Additionally, several drug candidates can induce adverse off-target effects on different IA tissues. To overcome these limitations, tissue-binding, nano-composite microgels as IA small molecule drug delivery vehicles were designed. Micron-scale poly(ethylene glycol) (PEG) hydrogels, presenting  cartilage- or synoviocyte-binding peptides and containing small molecule-loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) were synthesized using microfluidics technology. Microgels loaded with a model small molecule (rhodamine B) exhibited a sustained, near-zero order release over 16 days. Additionally, PEG microgels functionalized with synoviocyte- or cartilage-targeting peptides, presented specific binding to rabbit and human synoviocytes, and to bovine articular cartilage in vitro, respectively. Using a rat model of knee OA, microgels were shown to be retained in the IA space for at least 3 weeks and did not induce detectable joint degenerative changes as measured by EPIC-μCT and histology. Finally, histological analysis demonstrated that synoviocyte-binding microgels were found trapped within the synovial membrane and significantly increased the IA retention time of a model small molecule near infra-red dye in vivo. Overall, these results suggest that nano-composite PEG microgels presenting tissue-binding peptides could be a promising strategy to achieve tissue-localized drug delivery and prolonged IA retention of small molecule drugs for OA treatment.

]]> Laura Paige 1 1593014720 2020-06-24 16:05:20 1593014720 2020-06-24 16:05:20 0 0 event BioE PhD Defense Presentation- "Articular cartilage- and synoviocyte-binding small molecule drug delivery system for the intra-articular treatment of osteoarthritis" -Lina María Mancipe Castro

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2020-07-07T13:00:00-04:00 2020-07-07T15:00:00-04:00 2020-07-07T15:00:00-04:00 2020-07-07 17:00:00 2020-07-07 19:00:00 2020-07-07 19:00:00 2020-07-07T13:00:00-04:00 2020-07-07T15:00:00-04:00 America/New_York America/New_York datetime 2020-07-07 01:00:00 2020-07-07 03:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Stephen Robinson]]> 27917 Advisor:

Shuichi Takayama, PhD (Georgia Institute of Technology)

Committee:

Eva Dyer, PhD (Georgia Institute of Technology)

Melissa Kemp, PhD (Georgia Institute of Technology)

Nael McCarty, PhD (Emory University)

Krish Roy, PhD (Georgia Institute of Technology)

Microscale high-thoughput phenotypic assay to evaluate ECM remodeling in pulmonary fibrosis

            In fibrotic disease, dysregulation of matrix remodeling generates excessive deposition of fibrous extracellular protein that can interfere with the architecture and function of tissue. The pathogenic role of aberrant fibrin remodeling is particularly interesting in idiopathic pulmonary fibrosis (IPF), which has proven largely unresponsive to conventional anti-fibrosis therapies. Due to the substantial variety factors that combinatorially influence extracellular matrix (ECM) turnover, there exists the need for a phenotypic assay to evaluate cumulative effects involving cell-mediated fibrinolysis and collagen deposition. The goal of this project was to develop a novel in vitro assay that mimics fibroblast-mediated remodeling of the provisional fibrin matrix, in order to establish a model system for fibrotic scar formation and evaluate potential therapeutic compounds. 

            This work introduces and evaluates new methods to analyze ECM turnover in a high-throughput, label-free format. An aqueous two-phase printing technique was established to enable generation of microscale fibroblast-laden fibrin gels, which resemble the provisional fibrin matrix in wound healing. In a first variant of the assay, addition of exogenous plasminogen enabled cell-mediated activation of plasmin for gradual degradation of the fibrin matrix. A second variation of the assay implemented higher fibroblast seeding densities with serum-supplemented media to facilitate remodeling of the fibrin matrix through concurrent fibrinolysis and collagen deposition. Live-cell imaging provided time-course brightfield micrographs that were analyzed through an automated image processing protocol for high throughput evaluation of different stages of remodeling. Application of this assay allowed convenient evaluation of healthy and diseased donors of pulmonary fibroblasts and assessment of anti-fibrotic compounds to determine their effects on different stages of remodeling. 

            This analysis of fibroblast-mediated remodeling of fibrin demonstrated characteristics of fibrotic ECM remodeling that are not assayed in other in vitro models of fibrosis. By investigating the cumulative effects of fibrinolysis and collagen deposition on fibroblastic remodeling of fibrin, this assay may provide a new resource for advancing understanding of fibrosis pathogenesis and for evaluating potential anti-fibrosis therapeutics.

]]> Laura Paige 1 1591278722 2020-06-04 13:52:02 1591278722 2020-06-04 13:52:02 0 0 event BioE PhD Defense Presentation- "Microscale high-thoughput phenotypic assay to evaluate ECM remodeling in pulmonary fibrosis" - Stephen Robinson

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2020-06-16T10:00:00-04:00 2020-06-16T12:00:00-04:00 2020-06-16T12:00:00-04:00 2020-06-16 14:00:00 2020-06-16 16:00:00 2020-06-16 16:00:00 2020-06-16T10:00:00-04:00 2020-06-16T12:00:00-04:00 America/New_York America/New_York datetime 2020-06-16 10:00:00 2020-06-16 12:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Proposal Presentation- Andre Norfleet]]> 27917 Committee Members:

- Dr. Melissa Kemp (Advisor, BME, Georgia Tech)

- Dr. Manu Platt  (BME, Georgia Tech)

- Dr. Eberhard Voit (BME, Georgia Tech)

- Dr. Ravi Kane (ChBE, Georgia Tech)

- Dr. Craig Forest (ME, Georgia Tech)

- Dr. Sung-Jin Park (BME, Georgia Tech)

 

Metabolic and Bioelectric Crosstalk in Directed Differentiation and Spatial Patterning of iPSC-derived Cardiomyocytes

 

Bioelectric cell physiology and signaling have recently received much attention for their exerted control over multicellular regenerative and developmental patterning outcomes. More specifically, resting membrane potentials, ionic currents, and long-range electric fields define bioelectric signals that dictate non-excitable cell developmental patterning. Understanding bioelectric system dynamics and their relation to downstream developmental pattern trajectories would provide engineers the ability to design and manipulate multicellular systems to specified phenotypes. Efforts to understand these mechanisms are complicated because the Vmem-determining ion channels and gap junctions are also modulated by Vmem, resulting in complex system feedback. Development of a bioelectric computational simulation platform enables a realistic bottom-up bioelectric modeling approach in which the coordinated dynamics of passive and active ion fluxes dictate spatiotemporal bioelectric patterning dynamics. The overall objective of this project is to determine the role of ionic fluxes in the creation and maintenance spatiotemporal bioelectric patterns present in iPSC multicellular clusters. The central hypothesis is that metabolism influences bioelectrical patterning through pH, ATP, and cell cycle effects that direct subsequent multicellular properties during iPSC-cardiomyocyte differentiation. Ultimately, the objective of this project as executed in three aims will relate bioelectric signaling cues, cell metabolism, and intercellular communication to downstream spatiotemporal phenotypic trajectories and will further provide a foundational basis for assisted control interventions of spatiotemporal bioelectric dynamic outcomes and downstream phenotypic trajectories.

]]> Laura Paige 1 1591112645 2020-06-02 15:44:05 1591112645 2020-06-02 15:44:05 0 0 event BioE PhD Proposal Presentation- "Metabolic and Bioelectric Crosstalk in Directed Differentiation and Spatial Patterning of iPSC-derived Cardiomyocytes" -Andre Norfleet

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2020-06-12T14:00:00-04:00 2020-06-12T16:00:00-04:00 2020-06-12T16:00:00-04:00 2020-06-12 18:00:00 2020-06-12 20:00:00 2020-06-12 20:00:00 2020-06-12T14:00:00-04:00 2020-06-12T16:00:00-04:00 America/New_York America/New_York datetime 2020-06-12 02:00:00 2020-06-12 04:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- David Francis]]> 27917 Advisor: Susan Thomas, Ph.D. (Georgia Institute of Technology)

 

Committee:

Julie Champion, Ph.D. (Georgia Institute of Technology)

Mark Prausnitz, Ph.D. (Georgia Institute of Technology)

Krishnendu Roy, Ph.D. (Georgia Institute of Technology)

Edmund Waller, M.D., Ph.D. (Emory University)

 

Enhancing immune checkpoint blockade and cancer immunotherapy via tissue targeting and biomaterial nanoparticles

 

Immune checkpoint blockade (ICB) has emerged in recent years as one of the most promising new cancer therapies. However, a significant majority of patients receiving these therapies 1) do not respond, 2) experience adverse side effects, or 3) respond initially but relapse. Overcoming these limitations is therefore a critical hurdle in improving these treatments. Checkpoint pathways are active in both the tumor microenvironment and lymphoid tissues where they prevent T cell cytotoxic function and activation, respectively. While improving tumor and lymphoid delivery of these therapies offers a promising approach to advance the efficacy of ICB, clinical applications of ICB have so far only relied on systemic administrations, which often result in poor tumor and lymphoid accumulation. Additionally, administration of combination immunotherapies outside of ICB is challenging as many of these drugs are short-lived in vivo, are insoluble in aqueous solvents, and are not targeted to the cells of interest leading to off-target side effects. Given the current state of ICB therapy, the focus of this thesis work is to address the drug delivery barriers associated with conventional systemic administrations and non-targeted delivery of immune modulators.  This work explored two unique delivery strategies: one which proposes drugging tumor draining lymph nodes with ICB therapies by way of lymphatics using local rather than systemic administrations to enhance anti-tumor efficacy; and the second which proposes a novel drug-eluting ICB platform by engineering an antibody-nanoparticle conjugate system for improved T cell targeting and sustained delivery of small molecule immunotherapies.

 

]]> Laura Paige 1 1590765408 2020-05-29 15:16:48 1590765408 2020-05-29 15:16:48 0 0 event BioE PhD Defense Presentation- "Enhancing immune checkpoint blockade and cancer immunotherapy via tissue targeting and biomaterial nanoparticles" -David Francis

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2020-06-05T12:00:00-04:00 2020-06-05T14:00:00-04:00 2020-06-05T14:00:00-04:00 2020-06-05 16:00:00 2020-06-05 18:00:00 2020-06-05 18:00:00 2020-06-05T12:00:00-04:00 2020-06-05T14:00:00-04:00 America/New_York America/New_York datetime 2020-06-05 12:00:00 2020-06-05 02:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[VIRTUAL - 7th Annual BioE Day]]> 27195 Join us virtually to celebrate the Petit Institute's Bioengineering Interdisciplinary Graduate Program!

RSVP HERE

Attend via BlueJeans Link HERE

AGENDA

12 noon        Welcome and Opening Remarks - Hang Lu, Ph.D., Director, and Manu Platt, Ph.D., Deputy Director - BioEngineering Program
 
12:05 p.m.    "Journey to Bioengineering" - Shuichi Takayama, Ph.D. - Outstanding BioE Faculty Advisor; Introduced by Hannah Viola
 
12:45 p.m.    "Biosensors for Field Deployable Diagnostics" - Monica McNerney, Ph.D. - Outstanding BioE Thesis; Introduced by Mark Styczynski, Ph.D.
 
1:15 p.m.      Rapid Fire Presentations - 10 current BioE students to present
 
2:15 p.m.      "Securing a Job as a Ph.D. Student: A Few Pitfalls and Tactical Solutions" - Steven Schwaner, Ph.D., BioE Alum Class of 2019, Consultant, Exponent; Introduced by Ross Ethier, Ph.D.
 
2:45 p.m.      "Universal Brain-machine Interfaces Enabled by Flexible Scalp Electronics & Deep-learning” - Musa Mahmood, Doctoral Candidate - Outstanding BioE Paper; W. Hong Yeo, Ph.D., Advisor
 
3:15 p.m.      "Adhesion Analysis to Interrogate Extravasation Capacity of CD8 T Cells for Adoptive Cell Therapy" - Camila Camargo, Doctoral Candidate - Outstanding BioE Abstract; Susan Thomas, Ph.D., Advisor
 
3:30 p.m.      “Insect Pee: How Sharpshooters Excrete Ultrafast Fluid Droplets” - Elio Challita, Doctoral Candidate - Outstanding BioE Abstract; Saad Bhamla, Ph.D., Advisor
 
3:45 p.m.      "A Bioengineering Journey: Navigating Unique Challenges and Opportunities" - Ivana Parker, Ph.D., BioE Alum Class of 2015, Assistant Professor University of Florida; Introduced by Manu Platt, Ph.D.
 
4:15 p.m.      2020 Awards Announced – Outstanding Rapid Fire Presentation, Christopher Ruffin Leadership Award

4:30 p.m.       Virtual Happy Hour 

5:30 p.m.       Adjourn

]]> Colly Mitchell 1 1586796768 2020-04-13 16:52:48 1588188090 2020-04-29 19:21:30 0 0 event 2020-05-05T13:00:00-04:00 2020-05-05T18:30:00-04:00 2020-05-05T18:30:00-04:00 2020-05-05 17:00:00 2020-05-05 22:30:00 2020-05-05 22:30:00 2020-05-05T13:00:00-04:00 2020-05-05T18:30:00-04:00 America/New_York America/New_York datetime 2020-05-05 01:00:00 2020-05-05 06:30:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[GT Bioengineering Program Website]]>
<![CDATA[BioE PhD Proposal Presentation- Camila Camargo]]> 27917 Advisor:

Dr. Susan Thomas (Georgia Institute of Technology)

 

Committee Members:

Dr. Andrés García (Georgia Institute of Technology)

Dr. Krishnendu Roy (Georgia Institute of Technology)

Dr. Shuichi Takayama (Georgia Institute of Technology)

Dr. Edmund Waller (Emory University)

 

Adhesion analysis of CD8+ T cells using engineered microfluidic platforms to interrogate extravasation capacity for adoptive cell therapy

 

Adoptive cell therapy (ACT) has emerged as a powerful treatment option for patients with metastatic melanoma. Despite encouraging results with this treatment modality, responses are seen in only a minority of patients. It is now known that low patient rates of response are due to poor tumor-infiltrating lymphocytes (TIL) survival post transfer as well as poor trafficking of transferred cells to relevant tissues. In order for TILs to infiltrate disease tissue from the blood vasculature, they utilize a highly orchestrated adhesion cascade that begins with selectin-mediated rolling adhesion to endothelial cells, followed by integrin mediated firm adhesion and subsequent extravasation. These adhesion ligand-receptor interactions have been implicated in TIL homing, however, an outstanding problem in the field is a lack of understanding how TIL’s surface adhesion ligands initiate and sustain adhesion interactions with the tumor vasculature, and how this may lead to improved engraftment of TILs to the tumor microenvironment. As such, the overall objective of this project is to utilize engineered microfluidic devices that enable the interrogation of adhesive behavior of cells under relevant hemodynamic forces to 1) analyze how cell adhesion is regulated by different microenvironments of the tumor vasculature and 2) determine what adhesion receptors, cytokines, and activation markers are present in highly adhesive cells. My central hypothesis is that microfluidic devices can be implemented to mimic the hemodynamic environment of the tumor vasculature to interrogate cellular characteristics such as adhesion ligand expression, activation and differentiation state of TILs associated with adhesion in flow. This work will provide insight into which TIL’s subpopulation is the most appropriate for enhanced tumor homing for ACT.

]]> Laura Paige 1 1586527705 2020-04-10 14:08:25 1586527705 2020-04-10 14:08:25 0 0 event BioE PhD Proposal Presentation-  "Adhesion analysis of CD8+ T cells using engineered microfluidic platforms to interrogate extravasation capacity for adoptive cell therapy" -Camila Camargo

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2020-04-24T12:00:00-04:00 2020-04-24T14:00:00-04:00 2020-04-24T14:00:00-04:00 2020-04-24 16:00:00 2020-04-24 18:00:00 2020-04-24 18:00:00 2020-04-24T12:00:00-04:00 2020-04-24T14:00:00-04:00 America/New_York America/New_York datetime 2020-04-24 12:00:00 2020-04-24 02:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Bailey Hannon]]> 27917 Committee:

C. Ross Ethier, PhD, Co-Advisor (Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University)

Machelle Pardue, PhD, Co-Advisor (Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University)

Brandon Dixon, PhD (George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology)

Mark Prausnitz, PhD (Chemical and Biomolecular Engineering, Georgia Institute of Technology)

Brian Samuels, MD, PhD (Department of Ophthalmology, University of Alabama, Birmingham)

Stiffening the Posterior Rat Sclera to Provide Neuroprotection in Glaucoma

Glaucoma is the leading cause of irreversible blindness in the world, expected to affect approximately 80 million people by the year 2020. This degenerative optic neuropathy is characterized by retinal ganglion cell (RGC) death, optic nerve damage, and progressive vision loss. While the exact etiology remains elusive, elevated intraocular pressure (IOP) is a known risk factor and lowering IOP remains the only effective treatment. Elevated IOP causes deformation and remodeling of the optic nerve head (ONH) tissues, which in turn is thought to promote localized neurodegeneration. Computational and ex vivo studies have shown that scleral stiffness strongly influences deformation of the ONH, and that increasing the stiffness of the sclera surrounding the ONH (the peripapillary sclera) can significantly reduce these excessive strains. We hypothesize that by crosslinking the collagenous peripapillary sclera, we will reduce mechanical deformation in the ONH, which will in turn mitigate glaucomatous vision loss.

To investigate this hypothesis, we developed a safe and efficacious scleral stiffening treatment using the collagen crosslinking agent, genipin through ex vivo and in vivo experiments in healthy rat eyes. We then evaluated our treatment’s efficacy to prevent glaucomatous damage in a microbead rat model of ocular hypertension. Our results indicate that scleral stiffening protects against retinal thinning but does not show protective effects on visual or retinal function, nor preservation of RGC axons. Overall, these results demonstrate the feasibility of using genipin for a scleral stiffening treatment. The absence of a strong protective effect of genipin-induced scleral stiffening on RGC function and structure may be due to limitations in the glaucomatous rat model, in that our model does not mirror the slow progression, nor the moderate IOP elevation characteristic of clinical glaucoma.

]]> Laura Paige 1 1586268011 2020-04-07 14:00:11 1586268011 2020-04-07 14:00:11 0 0 event BioE PhD Defense Presentation- "Stiffening the Posterior Rat Sclera to Provide Neuroprotection in Glaucoma" -Bailey Hannon

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2020-04-20T14:00:00-04:00 2020-04-20T16:00:00-04:00 2020-04-20T16:00:00-04:00 2020-04-20 18:00:00 2020-04-20 20:00:00 2020-04-20 20:00:00 2020-04-20T14:00:00-04:00 2020-04-20T16:00:00-04:00 America/New_York America/New_York datetime 2020-04-20 02:00:00 2020-04-20 04:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Katherine Birmingham]]> 27917 Advisor:

Susan Thomas, PhD (Georgia Institute of Technology)

 

Committee:

Andrés García, PhD (Georgia Institute of Technology)

Gregory Lesinski, PhD, MPH (Emory University)

John McDonald, PhD (Georgia Institute of Technology)

Todd Sulchek, PhD (Georgia Institute of Technology)

 

Engineered Microfluidic Platforms to Enable the Interrogation of Metastatic Extravasation Under Physiologically Relevant Hydrodynamic Forces

 

Over 90% of all cancer-related deaths result from metastasis, a multistep process that occurs in the blood or lymphatic vasculature under hydrodynamic forces. During metastasis, cancer cells leave the primary tumor, intravasate into the circulatory or lymphatic system, circulate until they can extravasate, and take up residence in a secondary location of the body to form a metastatic tumor. In order to leave the vasculature during extravasation, circulating tumor cells utilize a highly orchestrated adhesion cascade that begins with rolling adhesion to endothelial cells under a high shear environment. This process is driven by interactions between endothelial-presented selectins and selectin ligands present on the circulating cell’s surface. These selectin-selectin ligand interactions have been implicated in cancer metastasis, however, an outstanding problem in the field is the lack of effective systems to study the role of wall shear stress and cellular molecular profiles in initiating and sustaining these interactions, and how this may lead to enhanced metastatic capacity of circulating tumor cells.

 

As such, the overall objective of this thesis is to engineer microfluidic platforms to permit the analysis of selectin-mediated adhesion and interrogation of cellular characteristics underlying selectin-selectin ligand interactions between the endothelium and metastatic cell subpopulations that occur during cancer dissemination in a tumor microenvironment. My central hypothesis is that microfluidic systems can be engineered to mimic the hemodynamic forces of the circulatory system or hydrodynamic forces of the lymphatic system, which can be used to interrogate cellular characteristics associated with adhesion in flow or the effects of altered microenvironments on metastasis.

]]> Laura Paige 1 1585670296 2020-03-31 15:58:16 1585670296 2020-03-31 15:58:16 0 0 event BioE PhD Defense Presentation-  "Engineered Microfluidic Platforms to Enable the Interrogation of Metastatic Extravasation Under Physiologically Relevant Hydrodynamic Forces" -Katherine Birmingham

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2020-04-14T14:00:00-04:00 2020-04-14T16:00:00-04:00 2020-04-14T16:00:00-04:00 2020-04-14 18:00:00 2020-04-14 20:00:00 2020-04-14 20:00:00 2020-04-14T14:00:00-04:00 2020-04-14T16:00:00-04:00 America/New_York America/New_York datetime 2020-04-14 02:00:00 2020-04-14 04:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Nicholas Bolus]]> 27917 Advisor:

Omer T. Inan, PhD (Georgia Institute of Technology)

 

Committee:

Young-Hui Chang, PhD (Georgia Institute of Technology)

Geza Kogler, PhD, CPO (Kennesaw State University)

Gregory Sawicki, PhD (Georgia Institute of Technology)

Aaron Young, PhD (Georgia Institute of Technology)

 

Systems for Noninvasive Assessment of Biomechanical Load in the Lower Limb

            Every move you make—and, yes, every step you take—is the result of action at a joint, and so proper joint function is pivotal to the way we explore and interact with the world around us. Unfortunately, joint function is often disrupted by injuries, chronic disorders, or neurological deficits, which can, in turn, disrupt quality of life. Many forms of joint dysfunction derive from adverse biomechanical loading conditions—that is, the forces and torques to which our limbs are subjected—and, thus, techniques for monitoring these loads during daily life may improve our understanding of how injuries and disorders arise and progress—and, most importantly, how best to treat them.

            The standard methods for assessing these loading conditions, however, are almost all benchtop-bound and confined to laboratories or clinics, so their utility in at-home or ambulatory settings—where they may be most impactful—is limited. In an attempt to address this void, in this work, we present three novel techniques for extracting information related to joint loading using a synthesis of noninvasive / wearable sensing and machine learning. First, we detail the development of an adjustable-stiffness ankle exoskeleton with multimodal sensing capabilities and use it to explore how humans interact with external elastic loading of the ankle during walking. Then, in an attempt to peer “under the skin,” we develop a novel form-factor for capturing joint sounds—the skin-surface vibrations produced by articulating structures internal to the joint—and demonstrate that these noninvasive measurements can be used to discriminate levels of axial loading at the knee. Finally, taking the concept of joint acoustics one step further, we introduce a new, active acoustics-based technique whereby the tensile loading of a particular tissue—the Achilles tendon—can be estimated by measuring the tissue’s mechanical response to a burst vibration on the skin surface. Using this approach, we are able to assess this loading state (and, by association, the net moment at the ankle) reliably across several activities of daily life, and, through a proof-of-concept study, we demonstrate how the technique can effectively translate to a fully wearable device.

            Collectively, the efforts reported in this thesis represent a novel, multi-path approach to assessing biomechanical loading states in the lower limb and the effects thereof. These tools and insights may serve as a basis for future development of wearable, accessible technologies for monitoring joint load during daily life, thereby reducing injury risk, tracking disease progress, assessing the efficacy of treatment, and accelerating recovery. 

Advisor:

Omer T. Inan, PhD (Georgia Institute of Technology)

 

Committee:

Young-Hui Chang, PhD (Georgia Institute of Technology)

Geza Kogler, PhD, CPO (Kennesaw State University)

Gregory Sawicki, PhD (Georgia Institute of Technology)

Aaron Young, PhD (Georgia Institute of Technology)

 

Systems for Noninvasive Assessment of Biomechanical Load in the Lower Limb

            Every move you make—and, yes, every step you take—is the result of action at a joint, and so proper joint function is pivotal to the way we explore and interact with the world around us. Unfortunately, joint function is often disrupted by injuries, chronic disorders, or neurological deficits, which can, in turn, disrupt quality of life. Many forms of joint dysfunction derive from adverse biomechanical loading conditions—that is, the forces and torques to which our limbs are subjected—and, thus, techniques for monitoring these loads during daily life may improve our understanding of how injuries and disorders arise and progress—and, most importantly, how best to treat them.

            The standard methods for assessing these loading conditions, however, are almost all benchtop-bound and confined to laboratories or clinics, so their utility in at-home or ambulatory settings—where they may be most impactful—is limited. In an attempt to address this void, in this work, we present three novel techniques for extracting information related to joint loading using a synthesis of noninvasive / wearable sensing and machine learning. First, we detail the development of an adjustable-stiffness ankle exoskeleton with multimodal sensing capabilities and use it to explore how humans interact with external elastic loading of the ankle during walking. Then, in an attempt to peer “under the skin,” we develop a novel form-factor for capturing joint sounds—the skin-surface vibrations produced by articulating structures internal to the joint—and demonstrate that these noninvasive measurements can be used to discriminate levels of axial loading at the knee. Finally, taking the concept of joint acoustics one step further, we introduce a new, active acoustics-based technique whereby the tensile loading of a particular tissue—the Achilles tendon—can be estimated by measuring the tissue’s mechanical response to a burst vibration on the skin surface. Using this approach, we are able to assess this loading state (and, by association, the net moment at the ankle) reliably across several activities of daily life, and, through a proof-of-concept study, we demonstrate how the technique can effectively translate to a fully wearable device.

            Collectively, the efforts reported in this thesis represent a novel, multi-path approach to assessing biomechanical loading states in the lower limb and the effects thereof. These tools and insights may serve as a basis for future development of wearable, accessible technologies for monitoring joint load during daily life, thereby reducing injury risk, tracking disease progress, assessing the efficacy of treatment, and accelerating recovery. 

]]> Laura Paige 1 1585585804 2020-03-30 16:30:04 1585585804 2020-03-30 16:30:04 0 0 event BioE PhD Defense Presentation-  "Systems for Noninvasive Assessment of Biomechanical Load in the Lower Limb" -Nicholas Bolus

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2020-04-10T15:00:00-04:00 2020-04-10T17:00:00-04:00 2020-04-10T17:00:00-04:00 2020-04-10 19:00:00 2020-04-10 21:00:00 2020-04-10 21:00:00 2020-04-10T15:00:00-04:00 2020-04-10T17:00:00-04:00 America/New_York America/New_York datetime 2020-04-10 03:00:00 2020-04-10 05:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Proposal Announcement- Jeremy Caplin]]> 27917 Advisor:

Andrés García, Ph.D. (Georgia Institute of Technology)

 

Committee:

Edward Botchwey, Ph.D. (Georgia Institute of Technology)

Rodney Donlan, Ph. D. (Centers for Disease Control and Prevention)

John Peroni, DVM, MS, DACVS (University of Georgia)

Nick Willett, Ph.D. (Georgia Institute of Technology)

 

Lysostaphin-delivering Hydrogels for Local Drug Delivery in Bone Infection Models

Biomaterial associated infections remain a significant problem for medical devices and account for over 1 million hospital cases per year. Current therapies to eliminate biofilm formation in medical devices have shown low levels of success due to the inherent resistance of the biofilm towards antimicrobial agents. Lysostaphin is an enzyme derived from Staphylococcus simulans that is responsible for cleaving the pentaglycine cross-links of the staphylococcal cell wall, leading to cell lysis, making it a potentially useful agent to eradicate infection in both sites of bacterial growth, as well as established biofilms. Additionally, hydrogels have proven to be an effective agent for the site-specific introduction and release of therapeutics due to their modularity and highly favorable mechanical properties. Thus, the objective of this project is to engineer a synthetic poly(ethylene glycol)-based hydrogel platform for the encapsulation and delivery of lysostaphin to the site of complex infection. This will be achieved through two specific aims: 1) Development of a two-stage established infection model to assess bacterial mitigation and fracture healing of lysostaphin-encapsulated hydrogels synergistically with systemic antibiotics for a murine femoral fracture infection and 2) Investigation of bactericidal and pro-regenerative properties of lysostaphin-encapsulated hydrogels in an ovine ulnar osteotomy infection model. We expect that the local, sustained release of lysostaphin provided through the hydrogel carrier will lead to significant reduction in bacterial counts, as well as restorative function to the bone tissue at the site of fracture. This will be analyzed as a therapeutic that can be coupled with other forms of antimicrobial delivery, specifically with systemic antibiotics, which we anticipate will act synergistically with the lysostaphin-encapsulated hydrogels to provide heightened therapeutic delivery and bacterial mitigation.

]]> Laura Paige 1 1584365258 2020-03-16 13:27:38 1584365258 2020-03-16 13:27:38 0 0 event BioE PhD Proposal Announcement-  "Lysostaphin-delivering Hydrogels for Local Drug Delivery in Bone Infection Models" -Jeremy Caplin

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2020-03-23T14:30:00-04:00 2020-03-23T16:30:00-04:00 2020-03-23T16:30:00-04:00 2020-03-23 18:30:00 2020-03-23 20:30:00 2020-03-23 20:30:00 2020-03-23T14:30:00-04:00 2020-03-23T16:30:00-04:00 America/New_York America/New_York datetime 2020-03-23 02:30:00 2020-03-23 04:30:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Proposal Presentation- Karen Martin]]> 27917 Advisor:                            

Andrés García, Ph.D.

Committee:

Edward Botchwey, Ph.D.

Nick Willett, Ph.D.

Levi Wood, Ph.D.

Esma Yolcu, Ph.D.

 

 

Biomaterial-directed mesenchymal stem cell immunomodulation for enhanced bone repair outcomes

The immunomodulatory and pro-regenerative functions of mesenchymal stem cells (MSC) make them an attractive cell source for use in regenerative medicine applications. However, clinical translation is hampered by poor control over MSC survival, localization, phenotype, and secretome upon transplantation in vivo, as well as an incomplete understanding of how therapeutically delivered MSC interact with the host immune system to promote positive wound healing outcomes. The objective of this project is to utilize hydrogel delivery vehicles to promote MSC survival and immunomodulation in vivo and to evaluate the immune responses to these hydrogel-MSC therapies in a bone repair environment. This will be achieved through two specific aims: (1) Integrin-specific hydrogels will be evaluated for their ability to promote MSC persistence and immunomodulatory functions upon injection in vivo in immunocompetent mouse models. As there are several known species differences between human and murine immune cells and MSC, biomaterial-directed MSC secretome production and immune cell interactions will be evaluated in both a murine model using murine MSC and a humanized mouse model using human MSC, allowing for direct comparisons between species. (2) The impact of hydrogel-delivered MSC on bone healing and immune cell recruitment and phenotype over time will be evaluated in a murine segmental bone defect model. Using a combination of mass cytometry and single cell RNA-sequencing, key immune cell subpopulations that drive positive biomaterial-delivered MSC-dependent bone repair outcomes will be identified. The results of this proposal will yield critical insights into MSC-immune cell interactions in vivo and identify a means of modulating these interactions through the use of biomaterial-based MSC delivery vehicles.

]]> Laura Paige 1 1583337165 2020-03-04 15:52:45 1583337165 2020-03-04 15:52:45 0 0 event BioE PhD Proposal Presentation- "Biomaterial-directed mesenchymal stem cell immunomodulation for enhanced bone repair outcomes" -Karen Martin

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2020-03-17T15:30:00-04:00 2020-03-17T17:30:00-04:00 2020-03-17T17:30:00-04:00 2020-03-17 19:30:00 2020-03-17 21:30:00 2020-03-17 21:30:00 2020-03-17T15:30:00-04:00 2020-03-17T17:30:00-04:00 America/New_York America/New_York datetime 2020-03-17 03:30:00 2020-03-17 05:30:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Anna Liu]]> 27917 Committee Members:

Todd Sulchek, PhD (Georgia Institute of Technology, Mechanical Engineering), Advisor

Krishnendu Roy, PhD (Georgia Institute of Technology, Biomedical Engineering), Co-Advisor

Edmund K. Waller, MD PhD (Emory University School of Medicine, Department of Hematology and Oncology)

Alexander Alexeev, PhD (Georgia Institute of Technology, Mechanical Engineering)

Mark Prausnitz, PhD (Georgia Institute of Technology, Chemical and Biomolecular Engineering) 

 

Convective intracellular macromolecule delivery for cell engineering applications

 

Efficient intracellular delivery of target macromolecules remains a major obstacle in cell engineering, cell labeling, and other biomedical applications. Current standard methods of intracellular delivery, such as viral transduction and electroporation, do not meet the growing needs in the cell engineering field for cost-effective, scalable, and efficient delivery that maintains cell viability. This thesis work has discovered the cell biophysical phenomenon of convective intracellular macromolecule delivery using mechanically-induced, transient cell volume exchange. Ultrafast microfluidic cell compressions (<1 ms) are used to cause brief, deformation-induced cell volume loss followed by volume recovery through uptake of extracellular fluid. Macromolecules suspended in the surrounding fluid enter the cell on convective fluid currents. Convective delivery is shown to bypass endosomal transport and is capable of achieving high intracellular delivery for a broad range of molecule types and sizes. Compression-induced cell volume exchange is shown to be dependent on strain rate, magnitude of compression, and cell physical properties. The results of this thesis have informed the design and optimization of a high-throughput microfluidic technology capable of efficiently delivering a wide variety of macromolecule payloads to various cell types while maintaining viability and proliferation. We harness this cell volume exchange behavior for convective intracellular delivery of large macromolecules of interest, including plasmids (>2 MDa) and particles (>30 nm), while maintaining high cell viability (>95%). Successful experiments in CRISPR-Cas9 gene editing and intracellular gene expression analysis demonstrate potential to overcome the most prohibitive challenges in intracellular delivery for cell engineering.

]]> Laura Paige 1 1582722797 2020-02-26 13:13:17 1582722797 2020-02-26 13:13:17 0 0 event BioE PhD Defense Presentation- "Convective intracellular macromolecule delivery for cell engineering applications" -Anna Liu

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2020-03-10T12:00:00-04:00 2020-03-11T14:00:00-04:00 2020-03-11T14:00:00-04:00 2020-03-10 16:00:00 2020-03-11 18:00:00 2020-03-11 18:00:00 2020-03-10T12:00:00-04:00 2020-03-11T14:00:00-04:00 America/New_York America/New_York datetime 2020-03-10 12:00:00 2020-03-11 02:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Kathleen Bates]]> 27917 Committee Members:

Hang Lu, PhD (Georgia Institute of Technology, Chemical and Biomolecular Engineering), Advisor

Gordon Berman, PhD (Emory University, School of Biology)

Daniel Goldman, PhD (Georgia Institute of Technology, School of Physics)

Patrick McGrath, PhD (Georgia Institute of Technology, School of Biology)

Mark Styczynski, PhD (Georgia Institute of Technology, Chemical and Biomolecular Engineering) 

 

Tools for Behavioral Phenotyping of C. elegans

 

Animal behavior is critical to survival and provides a window into how the brain makes decisions and integrates sensory information. A simple model organism that allows researchers to more precisely interrogate the relationships between behavior and the brain is the nematode C. elegans. However, current phenotyping tools have technical limitations that make observing, intervening in, and quantifying behavior in diverse settings difficult. In this thesis, I develop enabling technological systems to resolve these challenges. To address scaling issues in observation and intervention in long-term behavior, I develop a platform for long-term continuous imaging, online behavior quantification, and online behavior-conditional intervention. I show that this tool is easy to build and use and can operate in an automated fashion for days at a time. I then use this platform to understand the consequences of quiescence deprivation to C. elegans health. To quantify complex animal postures, and plant and stem cell aggregate morphology, I develop an app to enable fast, versatile and quantitative annotation and demonstrate that it is both ~ 130-fold faster and in some cases less error-prone than state-of-the-art computational methods. This app is agnostic to image content and allows freehand annotation of curves and other complex and non-uniform shapes while also providing an automated way to distribute annotation tasks. This tool may be used to generate ground truth sets for testing or creating automated algorithms. Finally, I quantify C. elegans behavior using an automated and bias-free quantitative analysis and map the worm’s behavioral repertoire across multiple physical environments that more closely mimic C. elegans’ natural environment. From this analysis, I identified subtle behaviors that are not easily distinguishable by eye and built a tool that allows others to explore our video dataset and behaviors in a facile way.  I also use this analysis to examine the richness of C. elegans behavior across selected environments and find that behavior diversity is not uniform across environments. This has important implications for choice of media for behavioral phenotyping, as it suggests that the appropriate media choice may increase our ability to distinguish behavioral phenotypes in C. elegans.

Together, these tools enable novel behavior experiments at a larger scale and with more nuanced phenotyping compared to currently available tools.

]]> Laura Paige 1 1582722152 2020-02-26 13:02:32 1582722152 2020-02-26 13:02:32 0 0 event BioE PhD Defense Presentation-  "Tools for Behavioral Phenotyping of C. elegans" Kathleen Bates

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2020-03-09T10:30:00-04:00 2020-03-09T12:30:00-04:00 2020-03-09T12:30:00-04:00 2020-03-09 14:30:00 2020-03-09 16:30:00 2020-03-09 16:30:00 2020-03-09T10:30:00-04:00 2020-03-09T12:30:00-04:00 America/New_York America/New_York datetime 2020-03-09 10:30:00 2020-03-09 12:30:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Ruxiu Liu]]> 27917 Ruxiu Liu
PhD Defense Presentation – BioE
February 24th, 2020, 9:00 AM - Pettit (MiRC) Room 102

 

Committee:

A. Fatih Sarioglu, Ph.D. (Georgia Institute of Technology - ECE) - Chair

Albert B. Frazier, Ph.D. (Georgia Institute of Technology - ECE)

Andrés García, Ph.D. (Georgia Institute of Technology - ME)

Omer Inan, Ph.D. (Georgia Institute of Technology - ECE)

Wilbur Lam, Ph.D. (Georgia Institute of Technology - BMED)

 

Electronic Antibody Microarrays for Label-free Immunophenotyping of Cell Populations

 

Immunophenotyping (i.e., identifying cell membrane proteins) is widely used to characterize cell populations in basic research and to diagnose diseases from surface biomarkers in the clinic. This process requires complex instruments such as flow cytometers or fluorescence microscopes, which are typically housed in centralized laboratories. In this work, we present a microfluidic technology that employs a network of integrated electrical sensors to identify cell subpopulations based on their membrane antigens in a quantitative manner. To realize this technology, we developed a scalable electronic sensor network called microfluidic CODES (microfluidic coded orthogonal detection by electrical sensing), which combines code division multiple access (CDMA), a spread spectrum telecommunications technique, with Coulter sensing for the distributed detection of cells at strategic nodes across the microfluidic device from a single electrical output. By integrating the Microfluidic CODES technique with microfluidic cell capture chambers pre-functionalized with antibodies against target antigens, the device achieves all-electronic cell immunophenotyping through combinatorial arrangement of antibody sequences along microfluidic paths. Our technology not only provides an integrated platform for label-free combinatorial immunophenotyping of cell populations against multiple antigen targets, but also is built on frugal hardware well suited for resource limited settings or point-of-care applications.

]]> Laura Paige 1 1581351664 2020-02-10 16:21:04 1581351664 2020-02-10 16:21:04 0 0 event BioE PhD Proposal Presentation- "Electronic Antibody Microarrays for Label-free Immunophenotyping of Cell Populations" - Ruxiu Liu

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2020-02-24T09:00:00-05:00 2020-02-24T11:00:00-05:00 2020-02-24T11:00:00-05:00 2020-02-24 14:00:00 2020-02-24 16:00:00 2020-02-24 16:00:00 2020-02-24T09:00:00-05:00 2020-02-24T11:00:00-05:00 America/New_York America/New_York datetime 2020-02-24 09:00:00 2020-02-24 11:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Proposal Presentation- Yirui Li]]> 27917 Advisor:

Julie Champion, Ph.D. (School of Chemical & Biomolecular Engineering, Georgia Institute of Technology)

Committee:

Shuichi Takayama, Ph.D. (Department of Biomedical Engineering, Georgia Institute of Technology)

Ravi Kane, Ph.D. (School of Chemical & Biomolecular Engineering, Georgia Institute of Technology)

Valeria Milam, Ph.D. (School of Materials Science and Engineering, Georgia Institute of Technology)

James Dahlman, Ph.D. (Department of Biomedical Engineering, Georgia Institute of Technology)

 

Engineering Recombinant Protein Vesicles for Delivery Applications

Recombinant proteins have emerged as promising building blocks for self-assembly of nanoparticle. Their versatility, accessible through genetic manipulation, and biocompatibility are key advantages compared with synthetic block copolymers. One example of recombinant protein materials is hollow vesicles self-assembled from recombinant fusion proteins containing thermoresponisve elastin like polypeptide (ELP). While synthetic nanoparticles typically require chemical conjugation or physical adsorption to incorporate biofunctional proteins, protein vesicles are made directly from biofunctional proteins. This prevents loss of protein structure and activity, and enables control over protein orientation. Vesicles use high affinity leucine zippers, ZE and ZR, to enable a range of different biofunctional proteins to be displayed on the surface at controlled density. The overall goal of this work is to translate protein vesicles into functional materials made from bioactive proteins with the required physical and biological properties for use as delivery vehicles.  For increased stability at physiological conditions, a photo-crosslinkable unnatural amino acid was incorporated into the ELP domain.  Vesicle size was reduced from micron scale to nano scale by tuning ionic strength and amino acid hydrophobicity. To demonstrate the potential as a modular platform for drug delivery and vaccine delivery, a HER2 targeting protein, DARPinG3, and model antigen protein, ovalbumin (OVA), will be fused ZE and incorporated into self-assembled vesicles. In addition to protein “cargo” assembled in the membrane, small molecule and nucleic acid cargos will be encapsulated in the vesicle lumen. Hydrophilic cargos, such as oligonucleotides, will require the ELP domain to be engineered to be charged during vesicle assembly. This work will be the first to make therapeutic protein vesicles, and will demonstrate the value of this platform in delivering a wide range of cargos with vastly different properties, ranging from small hydrophobic molecules, to nucleic acids and large, folded proteins

]]> Laura Paige 1 1581338069 2020-02-10 12:34:29 1581338069 2020-02-10 12:34:29 0 0 event BioE PhD Proposal Presentation- "Engineering Recombinant Protein Vesicles for Delivery Applications" Yirui Li

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2020-02-21T14:00:00-05:00 2020-02-21T16:00:00-05:00 2020-02-21T16:00:00-05:00 2020-02-21 19:00:00 2020-02-21 21:00:00 2020-02-21 21:00:00 2020-02-21T14:00:00-05:00 2020-02-21T16:00:00-05:00 America/New_York America/New_York datetime 2020-02-21 02:00:00 2020-02-21 04:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioEngineering Graduate Committee Meeting]]> 27917 The BioEngineering graduate committee will meet to review/approve program policies, program faculty applications and submitted student petitions.

]]> Laura Paige 1 1580135956 2020-01-27 14:39:16 1580135956 2020-01-27 14:39:16 0 0 event BioEngineering Graduate Committee Meeting

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2020-04-14T13:00:00-04:00 2020-04-14T14:00:00-04:00 2020-04-14T14:00:00-04:00 2020-04-14 17:00:00 2020-04-14 18:00:00 2020-04-14 18:00:00 2020-04-14T13:00:00-04:00 2020-04-14T14:00:00-04:00 America/New_York America/New_York datetime 2020-04-14 01:00:00 2020-04-14 02:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioEngineering Graduate Committee Meeting]]> 27917 The BioEngineering graduate committee will meet to review/approve program policies, program faculty applications and submitted student petitions.

]]> Laura Paige 1 1580135880 2020-01-27 14:38:00 1580135880 2020-01-27 14:38:00 0 0 event BioEngineering Graduate Committee Meeting

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2020-03-10T13:00:00-04:00 2020-03-10T14:00:00-04:00 2020-03-10T14:00:00-04:00 2020-03-10 17:00:00 2020-03-10 18:00:00 2020-03-10 18:00:00 2020-03-10T13:00:00-04:00 2020-03-10T14:00:00-04:00 America/New_York America/New_York datetime 2020-03-10 01:00:00 2020-03-10 02:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioEngineering Graduate Committee Meeting]]> 27917 The BioEngineering graduate committee will meet to review/approve program policies, program faculty applications and submitted student petitions.

]]> Laura Paige 1 1580135792 2020-01-27 14:36:32 1580135792 2020-01-27 14:36:32 0 0 event BioEngineering Graduate Committee Meeting

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2020-01-30T12:00:00-05:00 2020-01-30T13:00:00-05:00 2020-01-30T13:00:00-05:00 2020-01-30 17:00:00 2020-01-30 18:00:00 2020-01-30 18:00:00 2020-01-30T12:00:00-05:00 2020-01-30T13:00:00-05:00 America/New_York America/New_York datetime 2020-01-30 12:00:00 2020-01-30 01:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Proposal Presentation- Gilad Doron]]> 27917 Advisors:

Johnna Temenoff, PhD (Georgia Institute of Technology)

Robert Guldberg, PhD (University of Oregon)

 

Committee:

Nick Willett, PhD (Georgia Institute of Technology)

Levi Wood, PhD (Georgia Institute of Technology)

Christopher Evans, PhD (Mayo Clinic)

 

Modulation of Mesenchymal Stromal Cell Proliferation and Secretion for the Treatment of Osteoarthritis

 

Mesenchymal stromal cells (MSCs) are highly-secretory cells that are of great clinical interest due to their immunomodulatory and pro-regenerative properties when transplanted in vivo. Their secretory potential has been utilized to treat multiple orthopedic conditions, including osteoarthritis (OA), a degenerative condition that affects a significant portion of the adult population and has no disease-modifying treatments. Despite their promise, MSCs and other cell therapies that rely on secretory activity are limited by large doses, requiring cell culture strategies that both enable large-scale expansion of MSCs without comprising their paracrine activity. Although standard culture methods promote large-scale MSC expansion, none are designed to improve secretory potential following therapeutic administration. Thus, the overall objectives of this work are to (1) identify culture conditions that promote MSC proliferative and secretory activity, (2) utilize these conditions to develop novel substrates for MSC expansion and delivery, and (3) evaluate their improvements to MSC therapies for treating OA. MSC proliferation and paracrine activity have been shown to be sensitive to several physical conditioning methods, including forced aggregation and the material properties of their adhesive culture substrate. Therefore, screening these conditions could identify the parameters that critically modulate their expansion potential and immunomodulatory factor secretion. These critical parameters will be used to develop novel adhesive substrates that both promote MSC proliferation in vitro and enhance the secretion in vivo. Subsequent improvements to their ability to reduce the progression of OA will be assessed by intra-articular delivery of unmodified as well as genetically-modified MSCs into a small animal model for post-traumatic OA, where resulting degeneration of the knee joint will be quantified primarily using contrast-enhanced microcomputed tomography (uCT)-based methods. Overall, this work aims to improve the production of highly-secretory MSCs in a manner that that aids their development as therapies for treating degenerative diseases such as OA.

]]> Laura Paige 1 1579184668 2020-01-16 14:24:28 1579184668 2020-01-16 14:24:28 0 0 event BioE PhD Proposal Presentation- "Modulation of Mesenchymal Stromal Cell Proliferation and Secretion for the Treatment of Osteoarthritis"- Gilad Doron

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2020-01-30T10:00:00-05:00 2020-01-30T12:00:00-05:00 2020-01-30T12:00:00-05:00 2020-01-30 15:00:00 2020-01-30 17:00:00 2020-01-30 17:00:00 2020-01-30T10:00:00-05:00 2020-01-30T12:00:00-05:00 America/New_York America/New_York datetime 2020-01-30 10:00:00 2020-01-30 12:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioEngineering Program Faculty Meeting]]> 27917 The BioEngineering Program faculty meet regularly during the semester to address program policies, events and future research and academic directions.

]]> Laura Paige 1 1576698241 2019-12-18 19:44:01 1576698241 2019-12-18 19:44:01 0 0 event Program policies, events and directions to be discussed

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2020-04-28T12:00:00-04:00 2020-04-28T13:00:00-04:00 2020-04-28T13:00:00-04:00 2020-04-28 16:00:00 2020-04-28 17:00:00 2020-04-28 17:00:00 2020-04-28T12:00:00-04:00 2020-04-28T13:00:00-04:00 America/New_York America/New_York datetime 2020-04-28 12:00:00 2020-04-28 01:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioEngineering Program Faculty Meeting]]> 27917 The BioEngineering Program faculty meet regularly during the semester to address program policies, events and future research and academic directions.

]]> Laura Paige 1 1576688148 2019-12-18 16:55:48 1576688148 2019-12-18 16:55:48 0 0 event Program policies, events and directions to be discussed

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2020-03-12T12:00:00-04:00 2020-03-12T13:00:00-04:00 2020-03-12T13:00:00-04:00 2020-03-12 16:00:00 2020-03-12 17:00:00 2020-03-12 17:00:00 2020-03-12T12:00:00-04:00 2020-03-12T13:00:00-04:00 America/New_York America/New_York datetime 2020-03-12 12:00:00 2020-03-12 01:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioEngineering Program Faculty Meeting]]> 27917 The BioEngineering Program faculty meet regularly during the semester to address program policies, events and future research and academic directions.

]]> Laura Paige 1 1576687587 2019-12-18 16:46:27 1576687587 2019-12-18 16:46:27 0 0 event Program policies, events and directions to be discussed

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2020-02-04T11:00:00-05:00 2020-02-04T12:00:00-05:00 2020-02-04T12:00:00-05:00 2020-02-04 16:00:00 2020-02-04 17:00:00 2020-02-04 17:00:00 2020-02-04T11:00:00-05:00 2020-02-04T12:00:00-05:00 America/New_York America/New_York datetime 2020-02-04 11:00:00 2020-02-04 12:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Proposal Presentation- Dillon Brown]]> 27917 Advisors:

Machelle Pardue, Ph.D. (Georgia Institute of Technology)

C. Ross Ethier, Ph.D. (Georgia Institute of Technology)

Committee:

Brandon Dixon, Ph.D. (Georgia Institute of Technology)

Wilbur Lam, Ph.D. (Georgia Institute of Technology)

Rafael Grytz, Ph.D. (University of Alabama at Birmingham)

Biomechanics and Biochemistry of the Myopic Mouse Sclera

Most cases of human myopia, colloquially known as “nearsightedness”, are due to an excessive axial elongation of the eye that disrupts its balance of geometry and optics. Previous research has implicated the sclera (the white part of the eye) as the main determinant of overall eye shape and size through its role in mechanically resisting the imposed tensile stresses from the persistent and fluctuating intraocular pressure. It is widely accepted that visual cues guide changes in scleral composition, structure, and biomechanics through the development of most mammalian myopia. Importantly, the ultrastructure of collagen, the main tension-bearing biological molecule, has been observed to remain largely unchanged until after the eye has already elongated, which raises questions about how visual cues are being transmitted to the sclera and what structural molecules are changing to facilitate axial elongation. Altered dynamics of the charge-dense proteoglycan aggrecan have been observed in eyes developing myopia, but how this contributes to biomechanics, eye geometry, and myopia progression is not known. To explore aspects of these questions, I will be utilizing the mouse model. My first aim will address the applicability of compression testing and the application of a poroelastic material model to determine compressive, tensile, and hydraulic properties in the very small and thin mouse sclera, whose size precludes most standard biomechanical tests. With this methodology established, my second aim will focus on characterizing biomechanical and biochemical changes to the sclera through the development of myopia. In my third aim, I will use previously established methods to probe a mechanistic question about a potential signaling molecule, retinoic acid, and how it alters scleral composition and biomechanics.

 

]]> Laura Paige 1 1575557598 2019-12-05 14:53:18 1575557598 2019-12-05 14:53:18 0 0 event BioE PhD Proposal Presentation- "Biomechanics and Biochemistry of the Myopic Mouse Sclera"-  Dillon Brown

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2019-12-17T13:00:00-05:00 2019-12-17T15:00:00-05:00 2019-12-17T15:00:00-05:00 2019-12-17 18:00:00 2019-12-17 20:00:00 2019-12-17 20:00:00 2019-12-17T13:00:00-05:00 2019-12-17T15:00:00-05:00 America/New_York America/New_York datetime 2019-12-17 01:00:00 2019-12-17 03:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Proposal Presentation- Seleipiri Charles]]> 27917 Advisor:

Hang Lu, Ph.D. (Georgia Institute of Technology)

Committee:

Melissa Kemp, Ph.D. (Georgia Institute of Technology)

Zhexing Wen, Ph.D. (Emory School of Medicine)

Johnna Temenoff, Ph.D. (Georgia Institute of Technology)

Wilbur Lam, Ph.D. (Georgia Institute of Technology)

 

Microfluidic tools for studying development in embryos and brain organoids

   Development in multicellular organisms is a complex process requiring multiple intracellular and extracellular signaling events. High content screening tools enable the cellular and subcellular assessment of developmental changes which in turn have led to a variety of genetic, pharmacological and therapeutic screens involving multicellular organisms. Developing high-content screening tools for both multicellular systems require high resolution imaging of protein and gene expression changes, relatively large number of samples to better characterize inter and intra-populational differences, and multiplexed readouts using the same sample to obtain layered information about developmental changes. Microfluidics can address these challenges by enabling high magnification imaging, parallelization, rapid reagent delivery and exchange and lower reagent consumption. Hence, this thesis seeks to address high content screening challenges that affect the study of development in active areas of research in my lab using microfluidics:  C. elegans embryogenesis and cellular development of brain organoids. I will demonstrate this through three specific aims that involve developing and improving microfluidic-based technology for large-scale imaging and characterizing the sample of interest by incorporating assays for probing structural features and functionality. As a result, I will develop a microfluidic-based assay for conducting high resolution measurements of gene expression changes during C. elegans embryogenesis using single molecule fluorescence in situ hybridization (aim 1). Next, I will develop and optimize culture conditions for microfluidic-based culture of forebrain organoids and coculture of microglia and cerebral organoids (aim 2). Finally, I will develop assays for multiparametric and in situ assessment of immune cell and neuronal cell interactions in cerebral organoids (aim 3). Combining high throughput microfluidic technology with high content imaging tools will improve the characterization of factors affecting development in these two biological systems.

]]> Laura Paige 1 1575382288 2019-12-03 14:11:28 1575382288 2019-12-03 14:11:28 0 0 event BioE PhD Proposal Presentation-  "Microfluidic tools for studying development in embryos and brain organoids "- Seleipiri Charles

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2019-12-16T10:30:00-05:00 2019-12-16T12:30:00-05:00 2019-12-16T12:30:00-05:00 2019-12-16 15:30:00 2019-12-16 17:30:00 2019-12-16 17:30:00 2019-12-16T10:30:00-05:00 2019-12-16T12:30:00-05:00 America/New_York America/New_York datetime 2019-12-16 10:30:00 2019-12-16 12:30:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Michael Griffin]]> 27917 IBB 1128 (Suddath Seminar Room)

 

Advisor: David N. Ku, MD PhD (Georgia Institute of Technology)

 

Committee:

Cyrus K. Aidun, PhD (Georgia Institute of Technology)

C. Ross Ethier, PhD (Georgia Institute of Technology)

Shannon L. Meeks, MD (Emory University)

Susan N. Thomas, PhD (Georgia Institute of Technology)

 

High Shear Arterial Thrombosis: Microfluidic Diagnostics and Nanotherapeutics

Atherothrombosis is the causal event in acute myocardial infarction and stroke. These occlusive arterial thrombi require the confluence of high shear rates from a stenosis, exposure of mural collagen from a ruptured plaque cap, and the aggregation of platelets on elongated vWF. A functional assay of thrombotic occlusion would be able to diagnose the propensity of individual patients to occlude and determine patient-specific drug regimens. Current platelet function tests do not have the relevant fluid mechanics, collagen surface, or proper anticoagulant to mimic arterial thrombotic occlusion. I have created an improved microfluidic assay that includes all the above factors, uses a small amount of whole blood, and is validated against clinical thrombosis over two orders of magnitude in size. 

Antiplatelet therapies, such as aspirin and clopidogrel, have been developed to irreversibly inhibit platelet activation or binding. However, they do not work as intended for a large percentage of the population, as up to 60% of patients exhibit resistance to therapy per current non-specific platelet assays. Resistance persists even with dual antiplatelet therapy (DAPT). The poor therapeutic efficacy of current anti-platelet agents with their associated major bleeding risks indicate the need for both a functional thrombosis assay and improved antithrombotic agents.

The overall goal of this thesis is to develop a low variability device for clinical diagnostics and arterial thrombosis research. I hypothesize that the main sources of variability observed in previous microfluidic assays of thrombosis are due to three fundamental design factors of high relevance to arterial thrombosis. Secondly, I hypothesize that the endpoint of occlusion time in the improved assay will be sensitive to antiplatelet responsiveness. Finally, I hypothesize that such a device can be utilized to develop and evaluate new antithrombotic nanoparticle therapies. Both in vitro and in vivo models of thrombosis will be utilized to investigate the hypotheses in this thesis.

]]> Laura Paige 1 1574784175 2019-11-26 16:02:55 1574784175 2019-11-26 16:02:55 0 0 event BioE PhD Defense Presentation-  "High Shear Arterial Thrombosis: Microfluidic Diagnostics and Nanotherapeutics" -Michael Griffin

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2019-12-11T14:00:00-05:00 2019-12-11T16:00:00-05:00 2019-12-11T16:00:00-05:00 2019-12-11 19:00:00 2019-12-11 21:00:00 2019-12-11 21:00:00 2019-12-11T14:00:00-05:00 2019-12-11T16:00:00-05:00 America/New_York America/New_York datetime 2019-12-11 02:00:00 2019-12-11 04:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Tel Rouse]]> 27917 Advisor: Hang Lu, Ph.D. (Georgia Institute of Technology)

Committee:

Patrick McGrath, Ph.D. (Georgia Institute of Technology)

Mark Styczynski, Ph.D. (Georgia Institute of Technology)

Robert Butera, Ph.D. (Georgia Institute of Technology)

Yun Zhang, Ph.D. (Harvard University)

 

 

MICROFLUIDIC-BASED TOOLS AND METHODS FOR COMPLEX CHEMOSENSORY AND CHEMOTAXIS STUDIES IN C. ELEGANS

 

There is a great interest in studying behavior and the underlying biological basis for behaviors in small model organisms. Some properties of C. elegans that greatly facilitate genetic investigations are its small size, relatively simplistic ‘brain’, complex repertoire of behaviors, and ease of isogenic population studies. In order to take full advantage of these characteristics, it is desirable to have methods for analyzing behaviors of large populations of animals in well controlled environments. One set of behaviors extensively used to investigate numerous phenomena in neurobiology within C. elegans deals with the navigation of chemical environments (chemotaxis). Studies based on C. elegans chemotaxis are used in investigating chemosensation, innate preferences, learning, memory, and more. We have improved upon previous microfluidic and computer-vision technologies to advance C. elegans chemosensation and chemotaxis studies to answer more sophisticated biological questions. One developed method is a microfluidic device capable of monitoring animal neuronal activity in vivo while delivering multiple chemical stimuli to animals at sub-second speeds and in any desired order. This method facilitates investigations as to how complex environmental stimulus changes are encoded within a simple, well-characterized nervous system at relevant behavioral timescales. The second developed method is a microfluidic platform and accompanying software capable of tracking a population of C. elegans freely navigating well-controlled, spatial chemical environments over long timescales. Via this method, complete behavioral and stimulus experience history profiles can be generated for each animal within a population. This enables correlations to be made between acute chemotaxis behaviors and animal stimulus histories which provides unique opportunities for novel insights into C. elegans neurobiology studies. 

]]> Laura Paige 1 1574783928 2019-11-26 15:58:48 1574783928 2019-11-26 15:58:48 0 0 event BioE PhD Defense Presentation-  "MICROFLUIDIC-BASED TOOLS AND METHODS FOR COMPLEX CHEMOSENSORY AND CHEMOTAXIS STUDIES IN C. ELEGANS" -Tel Rouse

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2019-12-10T10:00:00-05:00 2019-12-10T12:00:00-05:00 2019-12-10T12:00:00-05:00 2019-12-10 15:00:00 2019-12-10 17:00:00 2019-12-10 17:00:00 2019-12-10T10:00:00-05:00 2019-12-10T12:00:00-05:00 America/New_York America/New_York datetime 2019-12-10 10:00:00 2019-12-10 12:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Proposal Presentation- Jeffrey Gau]]> 27917 Advisor:

Simon Sponberg, PhD (School of Physics & School of Biological Sciences, Georgia Institute of Technology)

 

Committee:

Saad Bhamla, PhD (School of Chemical & Biomolecular Engineering, Georgia Institute of Technology)

Nick Gravish, PhD (School of Mechanical & Aerospace Engineering, University of California, San Diego)

David Hu, PhD (Woodruff School of Mechanical Engineering, Georgia Institute of Technology)

Kurt Wiesenfeld, PhD (School of Physics, Georgia Institute of Technology)

 

Beyond resonance in insect flight: strain-dependent actuation of deformable oscillatory structures

 

Insect flight is one example of a broad class of systems in which locomotion is powered via rhythmic movements. The dogma of the insect flight literature is that insects resolve the high power requirements of flight by operating at resonance. However, evidence suggests that a resonance model is incomplete. For instance, many species have evolved “asynchronous muscle,” in which contraction is controlled by mechanical stretch and decoupled from neural inputs. The central hypothesis of this proposal is that a critical missing piece in understanding insect flight dynamics is the strain-dependent properties of muscle, which introduces kinematics-forcing coupling. Mechanical testing experiments and analytical modeling of the insect flight apparatus show that resonance exists, but wingbeat frequencies are far above resonance. Furthermore, muscle physiology experiments find that traditional muscles exhibit some of the same properties that enable asynchrony, suggesting that physiological properties exist on a gradient. The remainder of this thesis will utilize simulation and robophysical experiments to explore the interactions between components of the insect flight system (nervous system, mechanics, and muscle) to develop a unifying framework of insect flight, and more generally, strain-dependent actuation of deformable systems. Finally, biological experiments will artificially induce asynchronous behavior in a synchronous flight muscle.

]]> Laura Paige 1 1574695135 2019-11-25 15:18:55 1574695135 2019-11-25 15:18:55 0 0 event BioE PhD Proposal Presentation-  "Beyond resonance in insect flight: strain-dependent actuation of deformable oscillatory structures" - Jeffrey Gau

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2019-12-10T12:00:00-05:00 2019-12-10T14:00:00-05:00 2019-12-10T14:00:00-05:00 2019-12-10 17:00:00 2019-12-10 19:00:00 2019-12-10 19:00:00 2019-12-10T12:00:00-05:00 2019-12-10T14:00:00-05:00 America/New_York America/New_York datetime 2019-12-10 12:00:00 2019-12-10 02:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE Ph.D. Proposal Presentation - Mark Stathos]]> 27195 Advisor:

Ravi Kane, Ph.D., (School of Chemical & Biomolecular Engineering, Georgia Institute of Technology)

Committee:


"Engineering Tools to Promote and Characterize Wnt-Mediated Stem Cell Differentiation"

The Wnt signaling pathway plays an important role in the development of many tissues in the body from the very earliest stage of the process. However, the precise mechanisms of the pathway and the specific roles it has in development in the context of different tissue types remain poorly understood. This is in part due to the complexity of embryonic development and in part due to the hydrophobicity of Wnt ligands which renders them expensive and difficult to purify in a usable form.

To overcome issues associated with the use of natural Wnt ligands, we have developed a heterodimer of Fabs which bind to the Wnt co-receptors LRP6 and Frizzled. We have demonstrated that this dimer can activate Wnt signaling with an efficacy comparable to that of the natural ligand. We will explore the ability to improve upon this tool by linking these dimer units to create a multivalent construct with higher avidity for Wnt receptors and will test its ability to activate signaling even more potently.

To better characterize the downstream effects of Wnt signaling during the manufacturing of therapeutic cells, we are also generating CRISPR/Cas9 edited reporter iPSC lines which we hope will be able to detect the expression of Wnt-regulated marker genes with high sensitivity and specificity. Luminescent signals generated by these cell lines during directed differentiation into cardiomyocytes may be able to guide the optimization of the manufacturing process to produce cardiomyocytes with a more mature phenotype. These cells will also be equipped with an inducible suicide mechanism to enable their easy and selective removal for cell manufacturing applications involving co-culture with unedited cells.  

]]> Colly Mitchell 1 1574088986 2019-11-18 14:56:26 1574089584 2019-11-18 15:06:24 0 0 event BioE Ph.D. Proposal Presentation- "Engineering Tools to Promote and Characterize Wnt-Mediated Stem Cell Differentiation" - Mark Stathos

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2019-11-25T14:00:00-05:00 2019-11-25T16:00:00-05:00 2019-11-25T16:00:00-05:00 2019-11-25 19:00:00 2019-11-25 21:00:00 2019-11-25 21:00:00 2019-11-25T14:00:00-05:00 2019-11-25T16:00:00-05:00 America/New_York America/New_York datetime 2019-11-25 02:00:00 2019-11-25 04:00:00 America/New_York America/New_York datetime <![CDATA[Petit Institute website]]> Laura Paige - 404-385-6655

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<![CDATA[BioE PhD Defense Presentation- Sang-Eon Park]]> 27917 Advisor:
Robert E. Gross, M.D. Ph.D. (Georgia Institute of Technology/Emory University)

 

Committee:

Babak Mahmoudi, Ph.D. (Georgia Institute of Technology/Emory University)

Christopher J. Rozell, Ph.D. (Georgia Institute of Technology)

John T. Gale, Ph.D. (Emory University)

Joseph R. Manns, Ph.D. (Emory University)

 

 

Optimizing neuromodulation for temporal lobe epilepsy treatment based on a surrogate neural state model

 

            Temporal lobe epilepsy is the most prevalent form of medication-resistant epilepsy, and current electrical stimulation therapy has not been able to accomplish the goal of seizure-freedom. This underscores the need for a new target and a different approach with more effective neuromodulation for epilepsy treatment. The projections from the medial septum (MS) and its regulatory role on the hippocampus make it an attractive neuromodulation target. Optogenetics enables selective excitation or inhibition of individual genetically-defined neuronal subpopulations, and thus provides a chance to find a better target among neuronal subpopulations for inducing a greater therapeutic effect. I have exhaustively explored the effect of exciting or inhibiting different neuronal subpopulations in the normal rat medial septum by using optogenetic stimulation. As a result, MS optogenetic stimulation using hSynapsin promoter in combination with Channelrhodopsin-2 was well suited for modulating electrophysiological activity of the hippocampus.

            The conventional approach for preclinical studies requires a large amount of time and resources to find effective stimulation parameters and often fails due to the inter-subject variability in stimulation effect. As an alternative, I presented a novel data-driven approach which can optimize the neuromodulation more effectively and efficiently by investigating the stimulation effect on the surrogate neural state model. For the new approach, I implemented and demonstrated a variety of machine learning techniques to explore the stimulation effect, to describe the pathological neural states and to optimize the stimulation parameters. Specifically, first, I built a data-driven neural state model to estimate a seizure susceptibility based on electrophysiological recordings. The output of the model played a surrogate role by providing a metric which was regulated via the MS optogenetic stimulation. Second, I further increased the effectiveness of the stimulation by implementing in vivo Bayesian optimization which quickly finds the subject-specific optimal stimulation parameters. Finally, I tested whether modulating the surrogate neural state model affected the symptom of epilepsy (i.e. seizure). The treatment efficacy of the data-driven surrogate approach was compared to the stimulation with an empirically selected parameter set. The stimulation parameters to maximize the hippocampal theta (4-10Hz) power, which was a surrogate of the epileptic symptom, was more effective than the empirically selected parameter (7Hz) for the seizure suppression.

]]> Laura Paige 1 1571336815 2019-10-17 18:26:55 1571336815 2019-10-17 18:26:55 0 0 event BioE PhD Defense Presentation-  "OPTIMIZING NEUROMODULATION FOR TEMPORAL LOBE EPILEPSY TREATMENT BASED ON A SURROGATE NEURAL STATE MODEL" Sang-Eon Park

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2019-10-25T15:00:00-04:00 2019-10-25T17:00:00-04:00 2019-10-25T17:00:00-04:00 2019-10-25 19:00:00 2019-10-25 21:00:00 2019-10-25 21:00:00 2019-10-25T15:00:00-04:00 2019-10-25T17:00:00-04:00 America/New_York America/New_York datetime 2019-10-25 03:00:00 2019-10-25 05:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Proposal Presentation- Jacob Misch]]> 27917 Advisor:

Stephen Sprigle, PhD, PT (School of Mechanical Engineering, Georgia Institute of Technology)

 

Committee:

Aldo Ferri, PhD (School of Mechanical Engineering, Georgia Institute of Technology)
Frank Hammond III, PhD (School of Mechanical Engineering, Georgia Institute of Technology)
Ramakant Rambhatla, MBA (Vice President and Chief Engineer, Invacare Corp.)

Sharon Sonenblum, PhD (School of Mechanical Engineering, Georgia Institute of Technology)

 

Evaluation of Systemic Energy Losses in Manual Wheelchairs Using Intermittently-Propulsive Robotic Testbed

 

Mobility, independence, support, and safety all need to be balanced for a wheelchair to become a functional extension of the user. Ease of control and maneuverability are dictated by the mechanical efficiency; less efficient chairs require greater physical exertion, and repetitive and intense loads on the upper extremities can ultimately lead to injuries from overuse. Essentially, mechanical efficiency is reflective of the energetic propulsion effort to travel over-ground against frictional and inertial resistances. The 'optimal' wheel or frame choice is often unclear, especially because users have limited access to higher-end component options that are locked behind dated coding policies unrelated to performance, quality, or perceived value. The objective of this research is split into three aims: 1) to empirically characterize the cost of wheelchair propulsion, 2) to assess performance of various wheelchair configurations, and 3) to improve the current predictive dynamic model of wheelchair mobility to better emulate real-world use. This proposed work will require the Anatomical Model Propulsion System (AMPS), a robotic wheelchair-propelling apparatus that has been used to assess wheelchair performance in past studies. As human users utilize cyclic torque bursts to propel the chair, one goal of the proposed research is to reproduce this intermittently-propulsive behavior with the electromechanical AMPS to better imitate real-world use. The hypothesis is that intermittent propulsion and coasting deceleration will highlight frictional and inertial resistance differences between the wheelchairs. Ultimately, this research will help clinicians and manufacturers understand how configuration choices influence propulsive efforts to improve their classification techniques, and generally improve their existing design processes.

]]> Laura Paige 1 1570198210 2019-10-04 14:10:10 1570198210 2019-10-04 14:10:10 0 0 event BioE PhD Proposal Presentation- "Evaluation of Systemic Energy Losses in Manual Wheelchairs Using Intermittently-Propulsive Robotic Testbed" - Jacob Misch

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2019-10-18T13:00:00-04:00 2019-10-18T15:00:00-04:00 2019-10-18T15:00:00-04:00 2019-10-18 17:00:00 2019-10-18 19:00:00 2019-10-18 19:00:00 2019-10-18T13:00:00-04:00 2019-10-18T15:00:00-04:00 America/New_York America/New_York datetime 2019-10-18 01:00:00 2019-10-18 03:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Behnaz Yousefi]]> 27917 Advisor:

Shella Keilholz (Georgia Institute of Technology and Emory University)

 

Committee Members:

Dr Bruce Crosson (Emory University and Georgia State University)

Dr Eric Schumacher (Georgia Institute of Technology)

Dr Anabelle Singer (Georgia Institute of Technology and Emory University)

Dr Garth Thompson (Shanghai Tech University)

 

Quasi-periodic patterns of brain intrinsic activity

dominantly coordinate the functional connections in humans

Brain is a complex self-organizing biophysical system and intrinsically very active. How such intrinsic activity serves the purpose of self-organization in humans can be examined during resting-state with the functional magnetic resonance imaging (rsfMRI). As a metric of average coherent activity, the Pearson correlation between rsfMRI timeseries of brain areas, called functional connectivity (FC), can reflect aspects of self-organization. For example, based on the FC between pairs of areas, the cerebral cortex can be parcellated into a few resting-state networks (RSNs) or exhibit a few functional connectivity gradients (FCGs). Varied dynamic regimes of intrinsic coherent activity exist as well. If often and strong enough, they can give rise to the average metric of FC yet might entail aspects about self-organization not captured by FC, and their independent characterization can be insightful. Among such dynamic regimes are the spatiotemporal quasiperiodic patterns (QPPs). Each QPP is obtained by identifying and simply averaging a set of similar segments of rsfMRI scan. Whole-brain QPPs in humans are ~20s long and each involve a cycle of activation and deactivation of different areas with different timings, overall reminiscent of RSNs and FCGs, suggesting contribution to FC.

To robustly detect multiple QPPs, method improvements were implemented and applied to ~800 individuals of the Human Connectome Project dataset. Three primary QPPs were thoroughly characterized. Within these QPPs activity propagates along the functional gradients at the cerebral cortex and most subcortical regions, in a well-coordinated way, because of the consistencies and synchronies across all brain regions which reasonably accord with the consensus on the structural connections. Nuanced timing differences between regions and the closed flow of activity throughout the brain suggest drivers for these patterns. QPPs reflect neuronal activity, however, they also exhibit a principled relation with the slow variations in the respiration and heart rate and might basically be neurophysiological patterns. When three QPPs are removed from rsfMRI timeseries, FC within and particularly between RSNs remarkably reduces, illustrating their dominant contribution. Together, our results suggest a few recurring spatiotemporal patterns of intrinsic activity can dominantly coordinate the functional connections across the whole brain and serve self-organization. These intrinsic patterns possibly interact with the external tasks, affecting performance, or might provide more sensitive biomarkers in certain disorders and diseases.

]]> Laura Paige 1 1570023088 2019-10-02 13:31:28 1570113410 2019-10-03 14:36:50 0 0 event BioE PhD Defense Presentation-  "Quasi-periodic patterns of brain intrinsic activity dominantly coordinate the functional connections in humans"- Behnaz Yousefi

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2019-10-17T14:00:00-04:00 2019-10-17T16:00:00-04:00 2019-10-17T16:00:00-04:00 2019-10-17 18:00:00 2019-10-17 20:00:00 2019-10-17 20:00:00 2019-10-17T14:00:00-04:00 2019-10-17T16:00:00-04:00 America/New_York America/New_York datetime 2019-10-17 02:00:00 2019-10-17 04:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Mohammad Razavi]]> 27917 Committee Members: 


Dr. Rudolph L. Gleason (Advisor) - Department of Mechanical Engineering, GT

Dr. J. Brandon Dixon (Co-Advisor) - Department of Mechanical Engineering, GT

Dr. J. Alexander Alexeev - Department of Mechanical Engineering, GT

Dr. J. Wei Sun - Department of Biomedical Engineering, GT

Dr. David C. Zawieja - Department of Medical Physiology, Texas A&M

 

Mechanically Mediated Growth and Remodeling of Collecting Lymphatic Vessels

 

Lymphatic dysfunction plays a key role in pathologies such as immune disorders, infection, cancer, obesity, and cardiovascular disease; regarding the latter, lymphatic dysfunction may exacerbate edema in myocardial infarction (MI) and chronic heart failure. Secondary lymphedema is a progressive and debilitating disease characterized by fluid retention and tissue swelling that arises due to dysfunction in lymphatic pumping. Secondary lymphedema is a common complication in breast cancer treatment where the surgical removal of lymphatic vessels/lymph nodes can induce overloads that triggers lymphatic pathologies that can present months or even years after surgery. Although the local mechanical environment is known to regulate lymphatic function, the role of sustained mechanical overloads (e.g., high pressure and high flow) in lymphatic dysfunction has yet to be established. Towards this end, our long-term goal was to develop a mechanistic understanding of mechanically-mediated growth and remodeling (G&R) of collecting lymphatic vessels in health and disease and to ultimately identify novel therapeutic interventions to minimize the risk of occurrence, severity, or complications of lymphatic dysfunction.  This PhD thesis focuses on developing a novel rat tail model to study lymphatic G&R and to employ a combined experimental-computational approach to quantify the modes by which sustained high pressure and high flow compromise the normal function of the lymphatic system via maladaptive remodeling. First, we introduced and used a novel rat tail model to study the effect of mechanical loads (specifically axial stretch) on the lymphatic contractility. Second, we developed a computational framework to study lymphatic pumping in the context of a lymphangion chain. Third, we developed and tested the feasibility of a novel lymphatic ligation model to study lymphatic remodeling post-surgery. Lastly, the methods and results from this study can pave the way for future studies of lymphatic remodeling in health and disease.

 

]]> Laura Paige 1 1568900206 2019-09-19 13:36:46 1568900206 2019-09-19 13:36:46 0 0 event BioE PhD Defense Presentation - "Mechanically Mediated Growth and Remodeling of Collecting Lymphatic Vessels" - Mohammad Razavi

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2019-10-03T13:30:00-04:00 2019-10-03T16:00:00-04:00 2019-10-03T16:00:00-04:00 2019-10-03 17:30:00 2019-10-03 20:00:00 2019-10-03 20:00:00 2019-10-03T13:30:00-04:00 2019-10-03T16:00:00-04:00 America/New_York America/New_York datetime 2019-10-03 01:30:00 2019-10-03 04:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Song Ih Ahn]]> 27917 Advisor: YongTae (Tony) Kim, Ph.D. (Georgia Institute of Technology)

Committee:

Allan I. Levey, MD, Ph.D. (Emory University)

Mark R. Prausnitz, Ph.D. (Georgia Institute of Technology)

Shuichi Takayama, Ph.D. (Georgia Institute of Technology and Emory University)

Levi Wood, Ph.D. (Georgia Institute of Technology and Emory University)

]]> Laura Paige 1 1567084562 2019-08-29 13:16:02 1567084562 2019-08-29 13:16:02 0 0 event BioE PhD Defense Presentation-  DEVELOPMENT OF A MICROENGINEERED HUMAN BLOOD-BRAIN BARRIER MODEL WITH 3D ASTROCYTIC NETWORK- Song Ih Ahn

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2019-09-03T16:00:00-04:00 2019-09-03T18:00:00-04:00 2019-09-03T18:00:00-04:00 2019-09-03 20:00:00 2019-09-03 22:00:00 2019-09-03 22:00:00 2019-09-03T16:00:00-04:00 2019-09-03T18:00:00-04:00 America/New_York America/New_York datetime 2019-09-03 04:00:00 2019-09-03 06:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Proposal Presentation- Jimmy Ding]]> 27917 Advisor: Hang Lu, Ph.D. (Georgia Institute of Technology)

 

Committee:

J. Brandon Dixon, Ph.D. (Georgia Institute of Technology)

Patrick T. McGrath, Ph.D. (Georgia Institute of Technology)

Simon Sponberg, Ph.D. (Georgia Institute of Technology)

Lena H. Ting, Ph.D. (Georgia Institute of Technology, Emory University)

 

Investigating the mechanosensory mechanisms of two unique neuron groups in C. elegans

Mechanosensation is the basis for touch, hearing, and balance. It plays a vital role in how we navigate and operate in the world. Environmental information is taken by sensory neurons and converted into electrochemical signals, which are then conveyed and processed within a network of neurons to produce a relevant behavioral response. Caenorhabditis elegans are a microscopic nematode with a simple nervous system used as a model organism to study neural circuits, including the mechanosensory circuit. Previous work has identified and characterized several components of the mechanosensory circuit in C. elegans, including the proteins that make up the mechanotransductory ion channel in gentle touch neurons: proteins from the DEG/ENaC family, which are conserved in humans. Some behavioral and neuronal responses to simple mechanical stimuli are also known. However, the sensory response to complex, dynamic stimuli, and the mechanotransduction elements associated with such a response are still unknown. Furthermore, an entirely different set of mechanosensory neurons, dopamine releasing neurons, are known to have a unique and interconnected function with the rest of the mechanosensory circuit. These neurons do not express DEG/ENaC proteins, but instead express TRP-4, another protein homologous to mechanosensory proteins in higher organisms.   Little is known about how they function.  This thesis will use microfluidic, optical, and genetic techniques to apply temporally and spatially dynamic stimuli to C. elegans and characterize their neuronal response. Mutants with defects in mechanotransduction channel proteins, or neurotransmission in the different mechanosensory neurons, will be tested in the same manner to determine how different mechanotransduction components contribute to the mechanosensory circuit, and to reveal how the two neuron types interact. Stimuli will also be delivered to freely moving wild type and mutant animals, and their behavior will be characterized to determine how downstream outputs are affected by sensory neuronal capability and specificity. This work will provide insights into the mechanisms by which sensory neurons sense and process information, and how different types of sensory neurons work together to better process sensory information and produce relevant behaviors.

]]> Laura Paige 1 1567081027 2019-08-29 12:17:07 1567081027 2019-08-29 12:17:07 0 0 event BioE PhD Proposal Presentation-   :Investigating the mechanosensory mechanisms of two unique neuron groups in C. elegans" - Jimmy Ding

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2019-09-06T10:00:00-04:00 2019-09-06T12:00:00-04:00 2019-09-06T12:00:00-04:00 2019-09-06 14:00:00 2019-09-06 16:00:00 2019-09-06 16:00:00 2019-09-06T10:00:00-04:00 2019-09-06T12:00:00-04:00 America/New_York America/New_York datetime 2019-09-06 10:00:00 2019-09-06 12:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Stephen Schwaner]]> 27917 Advisor:

C. Ross Ethier, Ph.D., Department of Biomedical Engineering, Georgia Institute of Technology

Committee:

Andrés J. García, Ph.D., School of Mechanical Engineering, Georgia Institute of Technology

Rudolph L. Gleason, Ph.D., School of Mechanical Engineering, Georgia Institute of Technology

J. Brandon Dixon, Ph.D., School of Mechanical Engineering, Georgia Institute of Technology

Ian A. Sigal, Ph.D., Department of Bioengineering, University of Pittsburgh

 

Finite Element Modeling of Optic Nerve Head Biomechanics in a Rat Model of Glaucoma

Glaucoma is the leading cause of irreversible blindness and is characterized by the dysfunction of retinal ganglion cells (RGC), the cells that send vision information from the retina to the brain. All current therapies focus on lowering intraocular pressure (IOP), a causative risk factor in the disease. However, they are not always effective. Although it is well-accepted that elevated IOP-induced biomechanical insult to the optic nerve head (ONH), the region in the posterior eye where RGC axons exit, is key to glaucoma pathophysiology, the mechanisms by which biomechanical insult leads to RGC death are unknown. Rat glaucoma models present an opportunity for understanding glaucoma biomechanics and are widely used in the field. However, rat ONH biomechanics have not been characterized and rat ONH anatomy differs from the human.

Therefore, the purpose of this thesis was to provide the first characterization of rat ONH biomechanics to the glaucoma field. To this end, we completed three specific aims. First, we used inverse modeling combined with whole-eye inflation testing to extract material properties from the rat sclera. Second, we conducted a sensitivity study to investigate the effects of anatomical and material property variation on rat ONH strains using a parameterized finite element model of the rat ONH. Lastly, we developed a methodology for building rat ONH FE models with individual-specific geometry and simulated the effects of elevated IOP. Key results include the finding that the patterns of strain in the rat ONH are less symmetric than those in the human, and the highest strains occur in the inferior nerve. The results from this work can serve to inform future modeling studies on the rat ONH and provide context for interpreting rat glaucoma studies, with the goal of learning more about the link between biomechanical insult and RGC pathophysiology in glaucoma.

]]> Laura Paige 1 1563806697 2019-07-22 14:44:57 1563806697 2019-07-22 14:44:57 0 0 event BioE PhD Defense Presentation-  "Finite Element Modeling of Optic Nerve Head Biomechanics in a Rat Model of Glaucoma"-  Stephen Schwaner

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2019-08-05T15:00:00-04:00 2019-08-05T17:00:00-04:00 2019-08-05T17:00:00-04:00 2019-08-05 19:00:00 2019-08-05 21:00:00 2019-08-05 21:00:00 2019-08-05T15:00:00-04:00 2019-08-05T17:00:00-04:00 America/New_York America/New_York datetime 2019-08-05 03:00:00 2019-08-05 05:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Defense Presentation- Thomas Easley]]> 27917 Advisor:
Ajit P. Yoganathan, Ph.D. (Georgia Institute of Technology)

 

Committee:

Cyrus K. Aidun, Ph.D. (Georgia Institute of Technology)

Vasilis Babaliaros, M.D. (Emory University)

Joseph H. Gorman, M.D. (University of Pennsylvania)

Wei Sun, Ph.D. (Georgia Institute of Technology)

Vinod H. Thourani, M.D. (Georgetown University)

 

THE EFFECTS OF MITRAL ANNULAR DYNAMICS, AND THE LACERATION OF THE ANTERIOR LEAFLET WITH TRANSCATHETER MITRAL VALVE REPLACEMENTS

 

Restrictive annuloplasty rings are a standard mitral valve repair procedure for ischemic mitral regurgitation (MR), however there is a high incidence of recurrent MR. With this recurrent MR, there is a need to understand the restrictive effects from an annuloplasty on the MV leaflets. The first goal of this dissertation is to study the effects of annular dynamics on the mitral leaflets and its restriction. To accomplish this, an MV in vitro model with a dynamically contracting annulus will be designed and used to compare leaflet strain between varying contractile states. These, now, high-risk patients with failed MV repairs and replacements created a demand for percutaneous MV interventions. With no dedicated devices currently on the market, clinicians have resorted to placing transcatheter aortic valves (TAV) into mitral annular calcification (valve-in-MAC), failing mitral bioprosthetic valves (valve-in-valve), and failing mitral annuloplasty rings (valve-in-ring). Currently, there are no official clinical guidelines, and no quantitative engineering studies have been conducted to better understand performance and risks. Percutaneous laceration of the anterior mitral leaflet (LAMPOON) is a proposed proactive solution to the risk of left ventricular outflow tract (LVOT) obstruction. The second goal of this dissertation includes designing and performing in vitro experiments to evaluate and quantify benefits of LAMPOON on LVOT obstruction and thrombosis. These goals will provide insight into potential causes of recurrent MR with annuloplasty rings, and an in-depth quantitative assessment of the benefits of LAMPOON with transcatheter mitral valve replacements. These will better inform procedural guidelines and medical device design, as well as provide further insight into MV biomechanics and advanced platforms for future MV in vitro studies.

]]> Laura Paige 1 1560187553 2019-06-10 17:25:53 1560190348 2019-06-10 18:12:28 0 0 event BioE PhD Defense- "THE EFFECTS OF MITRAL ANNULAR DYNAMICS, AND THE LACERATION OF THE ANTERIOR LEAFLET WITH TRANSCATHETER MITRAL VALVE REPLACEMENTS"- Thomas Easley

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2019-06-24T10:00:00-04:00 2019-06-24T12:00:00-04:00 2019-06-24T12:00:00-04:00 2019-06-24 14:00:00 2019-06-24 16:00:00 2019-06-24 16:00:00 2019-06-24T10:00:00-04:00 2019-06-24T12:00:00-04:00 America/New_York America/New_York datetime 2019-06-24 10:00:00 2019-06-24 12:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Brett Klosterhoff]]> 27917 Advisors:

Bob Guldberg, Ph.D. (University of Oregon)

Nick Willet, Ph.D. (Atlanta VA Hospital/Emory Orthopaedics)

 

Thesis Committee Members:

Ed Botchwey, Ph.D. (Georgia Tech)

Scott. Hollister, Ph.D. (Georgia Tech)

Keat Ghee Ong, Ph.D. (Michigan Technological University)

Jeff Weiss, Ph.D. (University of Utah)

 

Mechanobiological Regulation of Early Stage Bone Repair

Each year in the United States alone, several hundred thousand people suffer skeletal fractures that do not heal from the original treatment, resulting in non-union. Patients with non-unions are afflicted with prolonged disability and often undergo multiple costly surgeries. To improve outcomes, there is a clinical need for therapeutic strategies that mitigate non-union risk by stimulating bone repair. As the primary load-bearing tissue, the skeleton dynamically adapts its structure to mechanical loads, and controlled loading via rehabilitation represents a non-pharmacologic target to stimulate bone formation. However, the study of mechanobiology in vivo has largely remained qualitative because the mechanical environment in the regenerative niche is difficult to monitor. This technical limitation hinders the ability to investigate mechanobiology and exploit it for therapeutic purposes.

The primary objectives of this thesis were to develop technical approaches to longitudinally monitor dynamic mechanical cues during bone healing and elucidate how specific magnitudes promote repair. To this end, we engineered a fully implantable wireless strain sensor platform that enabled real-time non-invasive monitoring of mechanical cues in a pre-clinical model of skeletal repair. We used the sensor platform and image-based finite element analyses to quantify the progression of mechanical cues during gait under varying degrees of load sharing. We discovered that early-stage strain magnitudes correlated with significantly improved healing outcomes. Furthermore, strain magnitudes correlated with the status of healing, demonstrating feasibility of strain sensing techniques as an X-ray-free healing assessment. Remarkably, we also observed that osteogenic mechanical loading exerted previously unexplored effects on early stage biological processes that precede mineralization, including immune cytokine signaling and angiogenesis.

The knowledge gained by this thesis aids the development of integrative therapeutic strategies that stimulate bone repair via rehabilitation. In addition, this thesis serves as foundational support for the expanded development of implantable sensors with broad implications to enhance diagnostics, therapeutic development, and interventional surveillance.

]]> Laura Paige 1 1560187103 2019-06-10 17:18:23 1560187103 2019-06-10 17:18:23 0 0 event BioE PhD Defense Presentation- "Mechanobiological Regulation of Early Stage Bone Repair"- Brett Klosterhoff

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2019-06-25T01:00:00-04:00 2019-06-25T15:00:00-04:00 2019-06-25T15:00:00-04:00 2019-06-25 05:00:00 2019-06-25 19:00:00 2019-06-25 19:00:00 2019-06-25T01:00:00-04:00 2019-06-25T15:00:00-04:00 America/New_York America/New_York datetime 2019-06-25 01:00:00 2019-06-25 03:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioEngineering Graduate Committee Meeting]]> 27917 The BioEngineering graduate committee will meet to review/approve program policies, program faculty applications and submitted student petitions.

]]> Laura Paige 1 1559225333 2019-05-30 14:08:53 1559225333 2019-05-30 14:08:53 0 0 event BioEngineering Graduate Committee Meeting

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2019-12-05T10:30:00-05:00 2019-12-05T11:30:00-05:00 2019-12-05T11:30:00-05:00 2019-12-05 15:30:00 2019-12-05 16:30:00 2019-12-05 16:30:00 2019-12-05T10:30:00-05:00 2019-12-05T11:30:00-05:00 America/New_York America/New_York datetime 2019-12-05 10:30:00 2019-12-05 11:30:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioEngineering Graduate Committee Meeting]]> 27917 The BioEngineering graduate committee will meet to review/approve program policies, program faculty applications and submitted student petitions.

]]> Laura Paige 1 1559225236 2019-05-30 14:07:16 1559225236 2019-05-30 14:07:16 0 0 event BioEngineering Graduate Committee Meeting

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2019-10-10T13:00:00-04:00 2019-10-10T14:00:00-04:00 2019-10-10T14:00:00-04:00 2019-10-10 17:00:00 2019-10-10 18:00:00 2019-10-10 18:00:00 2019-10-10T13:00:00-04:00 2019-10-10T14:00:00-04:00 America/New_York America/New_York datetime 2019-10-10 01:00:00 2019-10-10 02:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioEngineering Graduate Committee Meeting]]> 27917 The BioEngineering graduate committee will meet to review/approve program policies, program faculty applications and submitted student petitions.

]]> Laura Paige 1 1559225006 2019-05-30 14:03:26 1559225006 2019-05-30 14:03:26 0 0 event BioEngineering Graduate Committee Meeting

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2019-08-20T14:00:00-04:00 2019-08-20T15:00:00-04:00 2019-08-20T15:00:00-04:00 2019-08-20 18:00:00 2019-08-20 19:00:00 2019-08-20 19:00:00 2019-08-20T14:00:00-04:00 2019-08-20T15:00:00-04:00 America/New_York America/New_York datetime 2019-08-20 02:00:00 2019-08-20 03:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioEngineering Program Faculty Meeting]]> 27917 The BioEngineering Program faculty meet regularly during the semester to address program policies, events and future research and academic directions.

]]> Laura Paige 1 1559221823 2019-05-30 13:10:23 1559221823 2019-05-30 13:10:23 0 0 event Program policies, events and directions to be discussed

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2019-08-29T12:00:00-04:00 2019-08-29T13:00:00-04:00 2019-08-29T13:00:00-04:00 2019-08-29 16:00:00 2019-08-29 17:00:00 2019-08-29 17:00:00 2019-08-29T12:00:00-04:00 2019-08-29T13:00:00-04:00 America/New_York America/New_York datetime 2019-08-29 12:00:00 2019-08-29 01:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioEngineering Program Faculty Meeting]]> 27917 The BioEngineering Program faculty meet regularly during the semester to address program policies, events and future research and academic directions.

]]> Laura Paige 1 1559221620 2019-05-30 13:07:00 1559221620 2019-05-30 13:07:00 0 0 event Program policies, events and directions to be discussed

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2019-11-26T11:00:00-05:00 2019-11-26T12:00:00-05:00 2019-11-26T12:00:00-05:00 2019-11-26 16:00:00 2019-11-26 17:00:00 2019-11-26 17:00:00 2019-11-26T11:00:00-05:00 2019-11-26T12:00:00-05:00 America/New_York America/New_York datetime 2019-11-26 11:00:00 2019-11-26 12:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioEngineering Program Faculty Meeting]]> 27917 The BioEngineering Program faculty meet regularly during the semester to address program policies, events and future research and academic directions.

]]> Laura Paige 1 1559221508 2019-05-30 13:05:08 1559221508 2019-05-30 13:05:08 0 0 event Program policies, events and directions to be discussed

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2019-10-15T12:00:00-04:00 2019-10-15T13:00:00-04:00 2019-10-15T13:00:00-04:00 2019-10-15 16:00:00 2019-10-15 17:00:00 2019-10-15 17:00:00 2019-10-15T12:00:00-04:00 2019-10-15T13:00:00-04:00 America/New_York America/New_York datetime 2019-10-15 12:00:00 2019-10-15 01:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioEngineering Program Faculty Meeting]]> 27917 The BioEngineering Program faculty meet regularly during the semester to address program policies, events and future research and academic directions.

]]> Laura Paige 1 1546871608 2019-01-07 14:33:28 1559221390 2019-05-30 13:03:10 0 0 event Program policies, events and directions to be discussed

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2019-04-25T12:00:00-04:00 2019-04-25T12:00:00-04:00 2019-04-25T12:00:00-04:00 2019-04-25 16:00:00 2019-04-25 16:00:00 2019-04-25 16:00:00 2019-04-25T12:00:00-04:00 2019-04-25T12:00:00-04:00 America/New_York America/New_York datetime 2019-04-25 12:00:00 2019-04-25 12:00:00 America/New_York America/New_York datetime <![CDATA[]]>
<![CDATA[BioE PhD Defense Presentation- Timothy Lee]]> 27917 Advisor: 

Craig R. Forest, Ph.D., School of Mechanical Engineering, Georgia Institute of Technology

 

Committee:

R. Clay Reid, M.D., Ph.D., Allen Institute for Brain Science

Machelle T. Pardue, Ph.D., School of Biomedical Engineering, Georgia Institute of Technology

Peter J. Yunker, Ph.D., School of Physics, Georgia Institute of Technology

Todd A. Sulchek, Ph.D., School of Mechanical Engineering, Georgia Institute of Technology

 

Batch processing of brain tissue sections for millimeter-scale serial section transmission electron microscopy connectomics

The field of connectomics has emerged a promising approach for exploring the nature of neural circuits. A millimeter-scale connectome—a neuron-to-neuron wiring diagram of a neural circuit—potentially contains significant information regarding information processing and memory. The field is held back, however, by the difficulty in consistently and rapidly collecting neuroanatomical datasets with serial section transmission electron microscopy (ssTEM). In the cerebral cortex, for instance, a local circuit is contained in a cubic millimeter, but single sections—obtained by cutting brain samples with a diamond knife—must be “ultrathin” (< 40 nanometers), thus requiring 25,000 consecutive sections to be processed. Currently, the processing of ultrathin sections remains an unsolved problem that is necessary for the advancement of ssTEM connectomics. In this work, I (1) design, model, and test a novel device that uses hydrodynamic forces and curvature-induced capillary interactions for the transport and trapping of ultrathin sections, (2) design, implement, and characterize batch processing of single sections to enable reliable processing of thousands of serial sections, and (3) design, test, and characterize automated batched section processing, enabling high-throughput and reliable section processing. In total, this work outlines a novel platform for section processing for millimeter-scale ssTEM connectomics studies.

]]> Laura Paige 1 1558631037 2019-05-23 17:03:57 1558631037 2019-05-23 17:03:57 0 0 event BioE PhD Defense Presentation-  "Batch processing of brain tissue sections for millimeter-scale serial section transmission electron microscopy connectomics" - Timothy Lee 

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2019-06-13T15:00:00-04:00 2019-06-13T17:00:00-04:00 2019-06-13T17:00:00-04:00 2019-06-13 19:00:00 2019-06-13 21:00:00 2019-06-13 21:00:00 2019-06-13T15:00:00-04:00 2019-06-13T17:00:00-04:00 America/New_York America/New_York datetime 2019-06-13 03:00:00 2019-06-13 05:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[6th Annual BioE Day]]> 27195 Come celebrate the Petit Institute's Bioengineering Interdisciplinary Graduate Program!

AGENDA
12:30 p.m.     Posters in atrium - refreshments served

1:15 p.m.       Keynote Presentation - “Cast a Wide Net or Thread the Needle, Balancing Your BioE Skill Set for Success in Industry” - Ivan Cáceres, Ph.D., Senior Principal Data Analytics & Cognitive Autonomy Engineer, Northrop Grumman

2:15 p.m.       Rapid Fire

3:15 p.m.       Coffee break

3:30 p.m.       Graduate student presentation

3:40 p.m.       Graduate student presentation

3:50 p.m.       Graduate student presentation

4:00 p.m.       Outstanding Advisor Presentation - "Just (Bio)Eing Yourself" - Susan Thomas, Ph.D., Associate Professor, George W. Woodruff School of Mechanical Engineering

4:30 p.m.       Outstanding Paper Presentation - "Microfluidic Generation of Transient Cell Volume Exchange for Convectively Driven Intracellular Delivery of Large Macromolecules" - Anna Liu, doctoral candidate; Todd Sulchek, Ph.D., Advisor

5:00 p.m.       Awards

5:15 p.m.       Fun and Games on the Bioquad - refreshments served

]]> Colly Mitchell 1 1555502646 2019-04-17 12:04:06 1557404752 2019-05-09 12:25:52 0 0 event 2019-05-09T13:30:00-04:00 2019-05-09T20:00:00-04:00 2019-05-09T20:00:00-04:00 2019-05-09 17:30:00 2019-05-10 00:00:00 2019-05-10 00:00:00 2019-05-09T13:30:00-04:00 2019-05-09T20:00:00-04:00 America/New_York America/New_York datetime 2019-05-09 01:30:00 2019-05-09 08:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[GT Bioengineering Program Website]]>
<![CDATA[BioE PhD Defense Presentation- Josh Hooks]]> 27917 Advisor: 

J. Brandon Dixon, Ph.D. (ME/Georgia Institute of Technology)

 

Committee:

Andrés J. García, Ph.D. (ME/Georgia Institute of Technology)

C. Ross Ethier, Ph.D. (BME/(Georgia Institute of Technology)

Michael Davis, Ph.D. (BME/Georgia Institute of Technology & Emory University)

Mariappan Muthuchamy, Ph.D. (Medical Physiology/Texas A&M)


Title: The Role of Loading and the Microenvironment on the Regulation of Lymphatic Function and Health

Abstract:  

The lymphatic system is composed of vessels and nodes and exists in almost all of the soft tissue of your body. It plays a large role in maintain fluid homeostasis, immune cell trafficking, and lipid transport. Interstitial fluid that enters the lymphatic system through initial lymphatics is deemed “lymph” and is transported from wherever anatomical region it is collected to the blood circulation. Unlike the venous system, lymphatics  have no heart to act as a centralized pump and lymphatic vessels must act as the conduit for fluid flow and an active pump to drive lymph flow. Lymphatic dysfunction often leads to the development of swelling known as lymphedema. This buildup of fluid alters loading conditions of the local lymphatic network and lymphedema eventually leads to fibrosis and remodeling of the interstitium and lymphatic vessels. The relationship between how remodeling of these extracellular matrices (ECM) is a result of lymphatic dysfunction and/or drives further lymphatic dysfunction is not clearly understood. We present multiple studies utilizing engineering tools to better understand how the biomechanical properties and loading of the extracellular matrix regulate lymphatic function. We establish a healthy and disease lymphatic muscle cell (LMC) line and explore how LMC phenotype impact their response to 2D culture conditions. We demonstrate regulation of LMC molecular pathway expression via physiologically relevant levels of cyclic stretch. In addition, we demonstrate the use of modular polyethylene glycol (PEG) based hydrogels to explore the sensitivity of sprouting lymphangiogenesis to properties of the extracellular matrix. PEG gels can be formulated to produce a robust sprouting network that is sensitive to a variety of molecular regulator. Finally, we present results demonstrating that the PEG hydrogels can be used to successfully transplant lymphatic tissue after damage to local lymphatic collecting vessel or lymph nodes. Tissue transplanted with this method becomes functionally incorporated into the local lymphatic network.

 

]]> Laura Paige 1 1555597433 2019-04-18 14:23:53 1555597433 2019-04-18 14:23:53 0 0 event BioE PhD Defense Presentation-   "The Role of Loading and the Microenvironment on the Regulation of Lymphatic Function and Health"-  Josh Hooks

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2019-04-19T11:30:00-04:00 2019-04-19T13:00:00-04:00 2019-04-19T13:00:00-04:00 2019-04-19 15:30:00 2019-04-19 17:00:00 2019-04-19 17:00:00 2019-04-19T11:30:00-04:00 2019-04-19T13:00:00-04:00 America/New_York America/New_York datetime 2019-04-19 11:30:00 2019-04-19 01:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Proposal Presentation- Monica McNerney]]> 28778 Advisor: 

Dr. Mark Styczynski (Georgia Institute of Technology, Chemical & Biomolecular Engineering)

 

Committee:

Dr. Andreas Bommarius (Georgia Institute of Technology, Chemical & Biomolecular Engineering)

Dr. Brian Hammer (Georgia Institute of Technology, Biology)

Dr. Hang Lu (Georgia Institute of Technology, Chemical & Biomolecular Engineering)

Dr. Pamela Peralta-Yahya (Georgia Institute of Technology, Chemistry & Biochemistry)

 


Biosensor development for field-deployable diagnostics

Almost all current tests for biomarkers require venous blood draws, extensive sample processing, and analysis with complex equipment. Inexpensive, easy-to-use tests are critical for expanding healthcare to under-developed regions, but the requirement for reliable quantification in complex sample types (like blood) has been a critical roadblock in developing such diagnostics. Microbial-based biosensors have the potential to serve as a robust and generalizable platform for such diagnostics, as microbes can sense a wide variety of clinically relevant analytes and can produce colored outputs that are visible to the naked eye. Further, cell-free systems, which use bacterial protein extract to implement genetic networks, can be freeze-dried and rehydrated in the sample to be analyzed, enabling long-term storage at ambient temperatures and point-of-care test implementation and interpretation. This work describes the development of bacteria-based diagnostic assays that use bacterial sensing methods to control production of different colored readouts that are visible to the naked eye, yet quantitative and robust to the interference effects seen in complex samples. Using this platform, I develop a nearly field-deployable test for zinc deficiency (which is estimated to cause over 100,000 childhood deaths annually) that accurately measures clinically relevant zinc concentrations. The test requires just a finger-prick of blood, is robust to temperature variation, and can be freeze-dried for long term storage. I also use this approach to measure other classes of biomarkers, demonstrating a generalizable platform for low-cost quantitative diagnostics.

]]> Timothy Whelan 1 1554487956 2019-04-05 18:12:36 1554488172 2019-04-05 18:16:12 0 0 event BioE PhD Proposal Presentation "Biosensor development for field-deployable diagnostics"

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2019-04-19T14:00:00-04:00 2019-04-19T16:00:00-04:00 2019-04-19T16:00:00-04:00 2019-04-19 18:00:00 2019-04-19 20:00:00 2019-04-19 20:00:00 2019-04-19T14:00:00-04:00 2019-04-19T16:00:00-04:00 America/New_York America/New_York datetime 2019-04-19 02:00:00 2019-04-19 04:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Proposal Presentation- David Francis]]> 27917 Advisor: Susan Thomas, Ph.D. (Georgia Institute of Technology)

 

Committee:

Julie Champion, Ph.D. (Georgia Institute of Technology)

Mark Prausnitz, Ph.D. (Georgia Institute of Technology)

Krishnendu Roy, Ph.D. (Georgia Institute of Technology)

Edmund Waller, M.D., Ph.D. (Emory University)

 

Enhancing immune checkpoint blockade and cancer immunotherapy via tissue targeting and biomaterial nanoparticles

 

Immune checkpoint blockade (ICB) has emerged in recent years as one of the most promising classes of new cancer therapies. However, a significant majority of patients receiving these therapies 1) do not respond, 2) experience adverse side effects, or 3) respond initially but relapse. Overcoming these limitations is therefore a critical hurdle in improving cancer outcomes using ICB. To this end, immune checkpoints are active in both the tumor microenvironment and lymphoid tissues where they prevent T cell cytotoxic function and activation, respectively. To date, however, clinical applications of ICB have relied on systemic administration of free antibody drugs, which results in poor accumulation in tumors and lymphoid tissues and increases the risk of off target toxicities. Improving the selective delivery of ICB therapies to target tissues offers a promising approach to augment both the efficacy and safety of ICB. Moreover, upregulation of non-redundant immunosuppressive pathways is hypothesized to result in disease recurrence, motivating the use of combination immunotherapies to prevent relapse. However, many promising immunomodulatory agents that could work in synergy with ICB are small molecules and are thus short-lived in vivo, insoluble in aqueous solvents, and not targeted to the cells of interest. The objectives of this proposal, which will be demonstrated through impaired disease progression, diminution in treatment-associated toxicities, and protection against recurrence in multiple advanced preclinical mouse tumor models, are to 1) improve the effects of ICB within tumor and lymphoid tissues using various routes of administration and 2) develop a drug-eluting ICB platform that improves delivery of small molecule immunomodulators to T cells while simultaneously blocking immune checkpoint signaling.

]]> Laura Paige 1 1554300200 2019-04-03 14:03:20 1554300200 2019-04-03 14:03:20 0 0 event BioE PhD Proposal Presentation-  "Enhancing immune checkpoint blockade and cancer immunotherapy via tissue targeting and biomaterial nanoparticles"-  David Francis

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2019-04-16T11:00:00-04:00 2019-04-16T13:00:00-04:00 2019-04-16T13:00:00-04:00 2019-04-16 15:00:00 2019-04-16 17:00:00 2019-04-16 17:00:00 2019-04-16T11:00:00-04:00 2019-04-16T13:00:00-04:00 America/New_York America/New_York datetime 2019-04-16 11:00:00 2019-04-16 01:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE MS Thesis Presentation- JJ Obrien]]> 27917 Advisor:

Dr. Stephen Sprigle, Advisor (Georgia Tech, Industrial Design and Mechanical Engineering)

 

Committee:

Dr. Sharon Sonenblum (Georgia Tech, Mechanical Engineering)

Dr. Thomas Ploetz (Georgia Tech, College of Computing)

 

System Design of an Activity Tracker to Encourage Behavioral Change among Those at Risk of Pressure Ulcers

Electronic activity trackers are a common means by which to affect behavioral change. Whether they are aimed at physical fitness, patient compliance, or any other outcome, these activity trackers often aim to promote good behaviors and/or reduce harmful ones through the use of electronic monitoring devices. With the proliferation of mobile and ubiquitous computing in recent years, these systems have become more common than ever. The Wheelchair In-Seat Activity Tracker (WiSAT) is a system that began primarily as a research tool to monitor and track pressure ulcer prevention behaviors. This system relies upon data collected directly from sensors embedded in a wheelchair user’s cushion to identify when the user redistributes pressure from their buttocks or thigh. More recently, efforts have begun to transform the system into a consumer product. This objective was accomplished through the technical architecture of the app subsystem, systems integration between the subsystems, and the design and evaluation of the user-interface. This thesis describes the design and development process involved in converting WiSAT into a consumer activity tracker aimed at encouraging pressure ulcer prevention.

]]> Laura Paige 1 1553880098 2019-03-29 17:21:38 1553880098 2019-03-29 17:21:38 0 0 event BioE MS Thesis Presentation-  "System Design of an Activity Tracker to Encourage Behavioral Change among Those at Risk of Pressure Ulcers"- JJ Obrien

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2019-04-11T13:00:00-04:00 2019-04-11T15:00:00-04:00 2019-04-11T15:00:00-04:00 2019-04-11 17:00:00 2019-04-11 19:00:00 2019-04-11 19:00:00 2019-04-11T13:00:00-04:00 2019-04-11T15:00:00-04:00 America/New_York America/New_York datetime 2019-04-11 01:00:00 2019-04-11 03:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Proposal Presentation- Nicholas Bolus]]> 27917 Advisor

Omer T. Inan, PhD (Georgia Institute of Technology)

 

Committee:

Young-Hui Chang, PhD (Georgia Institute of Technology)

Geza Kogler, PhD, CPO (Georgia Institute of Technology)

Gregory Sawicki, PhD (Georgia Institute of Technology)

Aaron Young, PhD (Georgia Institute of Technology)

 

Joint Load Estimation Using Multimodal Wearable Sensing

Mechanical loading plays a key role in the pathogenesis and treatment of many forms of joint dysfunction. Proper manipulation of joint load is critical for accelerating rehabilitation from injury and improving assistive strategies for functional impairments. Tools to assess these loading conditions (e.g., joint torques, internal reaction forces, brace mechanics) are almost exclusively the domain of clinical and scientific research, and few techniques exist that are feasible for use in wearable, out-of-clinic settings. The focus of this work is to explore the use of wearable sensing approaches—in particular, instrumented orthoses and joint acoustical emissions—to estimate the loading conditions that affect joint function in the lower limbs. The latter, which involves detecting small skin-surface vibrations produced by joint articulation, has recently been demonstrated as a viable means of assessing the health status (e.g., injured vs. intact) of and mechanical stress borne by the knee. Successful completion of the proposed work will demonstrate that, by coupling joint acoustical information with that of other wearable sensors, joint loads can be estimated using accessible, noninvasive techniques, paving the way for longitudinal, at-home monitoring of joint health and function.

]]> Laura Paige 1 1553528629 2019-03-25 15:43:49 1553528629 2019-03-25 15:43:49 0 0 event BioE PhD Proposal Presentation-  "Joint Load Estimation Using Multimodal Wearable Sensing" - Nicholas Bolus

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2019-04-08T14:00:00-04:00 2019-04-08T16:00:00-04:00 2019-04-08T16:00:00-04:00 2019-04-08 18:00:00 2019-04-08 20:00:00 2019-04-08 20:00:00 2019-04-08T14:00:00-04:00 2019-04-08T16:00:00-04:00 America/New_York America/New_York datetime 2019-04-08 02:00:00 2019-04-08 04:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Aaron Enten]]> 27917 Advisor:

Dr. Todd A. Sulchek, Ph.D. (Georgia Institute of Technology, Mechanical Engineering)

Thesis Committee:

Dr. Craig R. Forest, PhD. (Georgia Institute of Technology, Mechanical Engineering)
Dr. Wilbur A. Lam, M.D. Ph.D. (Georgia Inst. of Technology | Emory University, Biomedical Engineering)

Dr. Manu Platt, Ph.D. (Georgia Inst. of Technology | Emory University, Biomedical Engineering)
Dr. Fatih Sarioglu (Georgia Inst. of Technology, Electrical and Computer Engineering)

 

Flow Rate Modulated Periodic Backflush to Improve Dead-End Filtration

 

Sorting modalities have been developed to achieve high enrichment factors, recovery rates, throughput, and purity. The negative downstream clinical impacts of labelled sorting mechanisms led groups to forego this option in favor of label-free methodologies. No device has yet to produce preferred results for all metrics, but some, especially filters, will realize most at the cost of one or two other metrics. Dead-end filters, specifically, are known for exceptionally large enrichment factors, purity, and throughput at the cost of recovery percentage or yield. Enabling filtration tools to eliminate or minimize these losses can have large impacts in diagnostic and therapeutic markets.

Pulse Width Modulation (PWM), a technique for controlling the proportionality of high to low signal (duty cycle), Pulse Amplitude Modulation (PAM), a technique for controlling the peak amplitude, and periodicity or frequency shifting of a square wave controlling volumetric flow rate and transmembrane pressure are shown to serve as novel techniques to increase recovery percentage in dead-end filtration systems while minimizing throughput tradeoffs. We employ these pulse modulation techniques to periodically backflush dead-end filters during sample processing for both biological and non-biological particulate suspensions and improve yield by interrupting cake formation, reintegrating fouling layers into the bulk of a sample, and improving permeate flux.

This thesis work initially investigates PWM theoretically and experimentally as a proof-of-concept for enabling the use of dead-end systems diagnostically and therapeutically. PWM backflush is then optimized through modulation of amplitude and frequency to minimize the costs to throughput. Finally, we apply the concept to conjugated microsphere recovery, bacterial isolation in a Cystic Fibrosis sorting model, and improve perfusion bioreactor scaffold seeding uniformity.

]]> Laura Paige 1 1552491425 2019-03-13 15:37:05 1552491425 2019-03-13 15:37:05 0 0 event BioE PhD Defense Presentation- "Flow Rate Modulated Periodic Backflush to Improve Dead-End Filtration" - Aaron Enten 

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2019-03-26T13:30:00-04:00 2019-03-26T15:30:00-04:00 2019-03-26T15:30:00-04:00 2019-03-26 17:30:00 2019-03-26 19:30:00 2019-03-26 19:30:00 2019-03-26T13:30:00-04:00 2019-03-26T15:30:00-04:00 America/New_York America/New_York datetime 2019-03-26 01:30:00 2019-03-26 03:30:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Immanuel David Madukauwa-David]]> 27917 Advisor:

Ajit P. Yoganathan, PhD (Georgia Tech, Biomedical Engineering)

 

Thesis Committee:

Vasilis Babaliaros, MD (Emory University, Medicine)

Rahul Sharma, MD (Cedars Sinai Medical Center, Stanford University)

Wei Sun, PhD (Georgia Tech, Biomedical Engineering)

John Oshinski, PhD (Georgia Tech, Biomedical Engineering)

Cyrus Aidun, PhD (Georgia Tech, Mechanical Engineering)

 

 

A Comprehensive Analysis of Potential Factors for Transcatheter Aortic Valve Thrombosis Risk

 

Transcatheter aortic valve replacement (TAVR) is indicated for aortic stenosis (AS) patients who are deemed intermediate or greater surgical risk. Recent evidence of leaflet thrombosis and reduced leaflet mobility in TAVR devices has led to concerns of stroke and long-term valve durability. Risk factors for thrombosis in TAVR patients remain poorly defined. While materials and blood chemistry are likely to be contributing factors to thrombosis risk, early clinical evidence and experimental data suggest that the fluid dynamic environment in the specific setting of the transcatheter aortic valve (TAV) is a major factor in the development of leaflet thrombosis. This environment can be altered by anatomical, procedural, and device related parameters. Additionally, it has been demonstrated that the thrombus originates in the “neo-sinus,” which is the pocket formed between the TAV leaflets and the native aortic valve leaflets.

This study, organized in three parts, aimed to elucidate the contribution of anatomical, deployment, and fluid dynamic factors to a thrombogenic environment in the neo-sinus region of transcatheter aortic valves via analyses of clinical imaging data and a battery of in vitro experiments on select commercial TAVs and their replicas. The first segment of this study demonstrated that certain aortic root anatomical dimensions and TAV deployment characteristics influence neo-sinus thrombus incidence and severity in TAVR patients as determined by an analysis of CT scans. In the second segment of this study, it was demonstrated by laser-induced fluorescence imaging that a higher implantation of the CoreValve improves neo-sinus fluid washout, and slight under-expansion of both the CoreValve and the SAPIEN 3 improve fluid washout of the region. Furthermore, these trends were replicated in a subset of experiments using an aortographic benchtop washout technique at normal and low cardiac outputs. An analysis of retrospective routinely-acquired clinical aortographic data confirmed the trend of TAV expansion yielding improved neo-sinus washout. This established aortography as a potential means of peri-procedurally evaluating TAVR patient flow-related thrombosis risk. The last segment of this study demonstrated that the TAV cusp most proximal to the native LCC has less flow stasis as a result of coronary flow in its vicinity compared to the TAV cusp proximal to the native NCC. This trend was seen in a supra-annular TAV replica and but not the intra-annular replica.

This thesis work facilitated an understanding of how certain anatomical and TAV deployment characteristics influence neo-sinus thrombosis risk and severity particularly with respect to the Virchow’s triad factor, flow stasis. These findings may be instrumental in improving patient outcomes as device deployment criteria and device design are finetuned in the near future.

]]> Laura Paige 1 1552397421 2019-03-12 13:30:21 1552397421 2019-03-12 13:30:21 0 0 event BioE PhD Defense Presentation- "A Comprehensive Analysis of Potential Factors for Transcatheter Aortic Valve Thrombosis Risk" - Immanuel David Madukauwa-David

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2019-03-29T10:00:00-04:00 2019-03-29T12:00:00-04:00 2019-03-29T12:00:00-04:00 2019-03-29 14:00:00 2019-03-29 16:00:00 2019-03-29 16:00:00 2019-03-29T10:00:00-04:00 2019-03-29T12:00:00-04:00 America/New_York America/New_York datetime 2019-03-29 10:00:00 2019-03-29 12:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Proposal Presentation- Katherine Birmingham]]> 27917 Advisor:

Dr. Susan Thomas (Georgia Institute of Technology)

 

Committee Members:

Dr. Andrés García (Georgia Institute of Technology)

Dr. Todd Sulchek (Georgia Institute of Technology)

Dr. John McDonald (Georgia Institute of Technology)

Dr. Gregory Lesinski (Emory University)

 

Engineered microfluidic platforms to enable the interrogation of metastatic extravasation under physiologically relevant hydrodynamic forces

 

Over 90% of all cancer-related deaths result from metastasis, a multistep process that occurs in either the lymphatics or in the blood vasculature. During metastasis, cancer cells leave the primary tumor, intravasate into the circulatory or lymphatic system, circulate until they are able to extravasate, and eventually take up residence in a secondary location of the body to form a metastatic tumor. In order to travel to distant sites in the body during the process of metastatic cancer extravasation, circulating tumor cells utilize a highly orchestrated adhesion cascade that begins with rolling adhesion to endothelial cells under a high shear environment. This process is driven by interactions between endothelial-presented selectins and glycan epitopes on selectin ligands present on the circulating cell’s surface. Selectin-selectin ligand interactions between circulating cancer cells and endothelial cells have been implicated in cancer metastasis, however, an outstanding problem in the field is the lack of effective systems to study the role of wall shear stress and cellular molecular profiles in initiating and sustaining increased selectin-ligand interactions, and how this may lead to enhanced metastatic propensity of circulating tumor cells. As such, the overall objective of this proposal is to engineer microfluidic platforms to permit the analysis of selectin-mediated adhesion and interrogation of cellular characteristics underlying selectin-selectin ligand interactions between the endothelium and metastatic cell subpopulations that occur during cancer dissemination in a tumor microenvironment. My central hypothesis is that microfluidic systems can be engineered to mimic the hemodynamic forces of the circulatory system or hydrodynamic forces of the lymphatic system, which can be used to interrogate cellular characteristics associated with adhesion in flow or the effects of altered microenvironments on metastasis.

]]> Laura Paige 1 1551196632 2019-02-26 15:57:12 1551196632 2019-02-26 15:57:12 0 0 event BioE PhD Proposal Presentation-  "Engineered microfluidic platforms to enable the interrogation of metastatic extravasation under physiologically relevant hydrodynamic forces"-  Katherine Birmingham

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2019-03-11T15:30:00-04:00 2019-03-11T17:30:00-04:00 2019-03-11T17:30:00-04:00 2019-03-11 19:30:00 2019-03-11 21:30:00 2019-03-11 21:30:00 2019-03-11T15:30:00-04:00 2019-03-11T17:30:00-04:00 America/New_York America/New_York datetime 2019-03-11 03:30:00 2019-03-11 05:30:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Proposal Presentation- Behnaz Yousefi]]> 27917 Advisor:

Shella Keilholz (Georgia Institute of Technology and Emory University)

 

Committee Members:

Dr Bruce Crosson (Emory University and Georgia State University)

Dr Eric Schumacher (Georgia Institute of Technology)

Dr Anabelle Singer (Georgia Institute of Technology and Emory University)

Dr Garth Thompson (Shanghai Tech University)

 

Quasi-periodic patterns of the brain’s intrinsic activity and their contribution to functional connectivity, cortical and sub-cortical dynamics, and behavioral correlates

The intrinsic activity of the brain exhibits varied dynamics, among which are the infra-slow quasiperiodic spatiotemporal patterns (QPPs). In humans, QPPs involve a ~20s cycle of activation and deactivation of the macroscale networks. Because of the specific dynamics within each QPP, they are likely to be influential contributors to the widely used measures based on the functional connectivity (FC). Intrinsic FC between and within the macroscale networks can predict behavioral traits and states or can be used as biomarker for psychiatric disorders and neurological diseases. Therefore, a better understanding of the contributing patterns to the intrinsic FC entails significance. This project aims to: 1. Improve the method to detect QPPs, examine their relationship with the physiological fluctuations and head motion, and show the extent of their contribution to the functional connectivity by regression. 2. Characterize the dynamics within QPPs at the cortical and subcortical regions, in terms of patterns of coactivity or propagation of activity, compare the results with the existing FC-based parcellations or gradients, and specify the novel messages revealed by QPPs about the intrinsic macroscale functional organization of the brain. 3. Examine the behavioral correlates of QPPs by relating the cognitive and psychological measures to various QPP metrics.

]]> Laura Paige 1 1550775585 2019-02-21 18:59:45 1550775585 2019-02-21 18:59:45 0 0 event BioE PhD Proposal Presentation-  "Quasi-periodic patterns of the brain’s intrinsic activity and their contribution to functional connectivity, cortical and sub-cortical dynamics, and behavioral correlates" - Behnaz Yousefi

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2019-03-01T09:00:00-05:00 2019-03-01T11:00:00-05:00 2019-03-01T11:00:00-05:00 2019-03-01 14:00:00 2019-03-01 16:00:00 2019-03-01 16:00:00 2019-03-01T09:00:00-05:00 2019-03-01T11:00:00-05:00 America/New_York America/New_York datetime 2019-03-01 09:00:00 2019-03-01 11:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Proposal Presentation- Timothy Sowers]]> 27917 Advisor:

Dr. Stanislav Emelianov (Georgia Institute of Technology, Emory University)

 

 

Committee Members:

Dr. Brooks Lindsey (Georgia Institute of Technology, Emory University)

Dr. David Ku (Georgia Institute of Technology)

Dr. Muralidhar Padala (Emory University, Georgia Institute of Technology)

Dr. Levent Degertekin (Georgia Institute of Technology)

 

 

Diagnosis and Characterization of Atherosclerotic Plaques with Photoacoustic Imaging

 

Cardiovascular disease is the primary cause of death worldwide.  Coronary artery disease, a subset of cardiovascular disease, caused an estimated 7.4 million deaths in 2015.  Physicians' inability to accurately locate plaques is a current impediment to diagnosis and treatment.  Photoacoustics is being developed to address this deficiency.  Photoacoustic imaging is a technique in which nanosecond laser pulses are used to locally heat tissue, producing a thermal expansion and resultant ultrasonic wave that can be measured with an ultrasound transducer.  The intensity of the ultrasonic signal is proportional to the tissue’s optical absorption coefficient, which will vary by tissue type and light wavelength.  Thus, the distinct optical spectra of lipid make it an identifiable marker of atherosclerotic plaques.  The work that will be proposed for this dissertation consists of advancing photoacoustic imaging of atherosclerotic plaques with three specific aims.  First, Monte Carlo simulations will be conducted to determine the optimal geometry for imaging using an ultrasound array and external light delivery.  Second, the safety of intravascular photoacoustic imaging, a catheter-based technique, will be assessed to determine if light absorption is likely to cause tissue damage.  Third, nanoscale contrast agents that enhance photoacoustic identification of lipid plaque will be tested. 

]]> Laura Paige 1 1549989816 2019-02-12 16:43:36 1549989816 2019-02-12 16:43:36 0 0 event BioE PhD Proposal Presentation-  "Diagnosis and Characterization of Atherosclerotic Plaques with Photoacoustic Imaging" - Timothy Sowers

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2019-02-27T13:00:00-05:00 2019-02-27T15:00:00-05:00 2019-02-27T15:00:00-05:00 2019-02-27 18:00:00 2019-02-27 20:00:00 2019-02-27 20:00:00 2019-02-27T13:00:00-05:00 2019-02-27T15:00:00-05:00 America/New_York America/New_York datetime 2019-02-27 01:00:00 2019-02-27 03:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Dennis Zhou]]> 27917 Thesis Committee:

Andrés J. García, PhD (ME, Advisor)

Aránzazu del Campo, PhD (Leibniz Institute for New Materials)

Jennifer Curtis, PhD (Physics)

Andrew Kowalczyk, PhD (Emory)

Cheng Zhu, PhD (BME)

 

Force-Signaling Coupling at Single Focal Adhesions

 

Integrin-mediated adhesion to extracellular matrices (ECM) provides forces and signals that direct cell processes central to tissue organization, homeostasis, and disease. Recent studies show an important relationship between cell adhesive force generation and focal adhesion (FA) assembly, yet it remains unclear how forces are transduced into adhesive signals. Our work seeks to assess coupling between cell adhesive force generation and signaling at FAs. To measure forces, we used Microfabricated Post-Array-Deflectors (mPADs), which are an array of PDMS ~1.8 µm diameter microposts. Based on the micropost deflections, we can calculate the forces exerted by cells. We first examined the relationship between traction force and vinculin-paxillin localization to single FAs in the context of substrate stiffness and actomyosin contractility. Substrate stiffness and contractility regulated vinculin localization to FAs, and vinculin auto-inhibition is a crucial regulatory step in this process that overrides the effects of cytoskeletal tension and substrate stiffness. Vinculin and paxillin FA area did not correlate with traction force magnitudes at single FAs, and this was consistent across different ECM stiffness and cytoskeletal tension states. Vinculin residence time at FAs linearly varied with applied force for stiff substrates, but this coupling was disrupted on soft substrates and in the presence of contractility inhibitors. In contrast, paxillin residence time at FAs was independent of force, substrate stiffness, and cytoskeletal contractility.

 

We also found that pFAK Y397 levels are linearly coupled to force at single FAs on stiff substrates. On soft substrates, however, this positive relationship is eliminated. We found that talin is required for FAK localization and Y397 phosphorylation at FAs and mediates force-FAK linear coupling at FAs via talin-FAK binding.  Furthermore, averaged levels of FAK localization and Y397 phosphorylation at FAs are relatively insensitive to vinculin expression. However, a full-length vinculin molecule that binds talin and actin is required for linear coupling to occur between force-FAK localization and force-FAK Y397 phosphorylation at individual FAs. Lastly, we demonstrate that a full-length vinculin molecule that binds talin and actin is required to promote YAP nuclear accumulation. These findings show that force generation and signaling are coupled at FAs and underscore the role of environmental stiffness, talin, and vinculin in regulating force-signaling coupling at FAs. This understanding provides a framework for mechanotransduction events at cell-ECM junctions, such as force-regulated morphogenesis and stem cell commitment in response to matrix stiffness.

 

 

]]> Laura Paige 1 1549550678 2019-02-07 14:44:38 1549550678 2019-02-07 14:44:38 0 0 event BioE PhD Defense Presentation-  "Force-Signaling Coupling at Single Focal Adhesions" -Dennis Zhou

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2019-02-21T08:30:00-05:00 2019-02-21T10:30:00-05:00 2019-02-21T10:30:00-05:00 2019-02-21 13:30:00 2019-02-21 15:30:00 2019-02-21 15:30:00 2019-02-21T08:30:00-05:00 2019-02-21T10:30:00-05:00 America/New_York America/New_York datetime 2019-02-21 08:30:00 2019-02-21 10:30:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Proposal Presentation- Nicholas Beskid]]> 27917 Tolerized Dendritic Cells Delivered via PEG-4MAL Hydrogels for Amelioration of Multiple Sclerosis

 

Multiple Sclerosis (MS) is an autoimmune disease that causes neurodegeneration and destruction of myelin in the CNS, resulting in physical and cognitive impairments. Currently there is no cure for MS and present treatment strategies can only slow disease progression and come with a myriad of complicated side effects. The purpose of this project is to (1) elucidate structure-function relationships between PEG-4MAL scaffolds and encapsulated dendritic cells (DCs), (2) incorporate adhesive and immunological cues to promote sustained function of tolerogenic DCs post-injection, and (3) evaluate the efficacy of hydrogel-delivered tolerogenic DCs to ameliorate autoimmune disease in a murine model of MS. Work outlined herein will uncover previously uncharacterized relationships between mechanical and adhesive properties of matrices on DC tolerogenicity for informed design of biomaterial delivery strategies. Proposed work will also provide a proof-of-concept treatment strategy for antigen-specific, DC-mediated treatment of MS. Immunological studies are expected to illustrate underlying mechanisms of amelioration and provide insight for further development of treatment strategies against autoimmunity.

 

]]> Laura Paige 1 1549398891 2019-02-05 20:34:51 1549398891 2019-02-05 20:34:51 0 0 event BioE PhD Proposal Presentation-  "Tolerized Dendritic Cells Delivered via PEG-4MAL Hydrogels for Amelioration of Multiple Sclerosis" - Nicholas Beskid

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2019-02-19T15:00:00-05:00 2019-02-19T17:00:00-05:00 2019-02-19T17:00:00-05:00 2019-02-19 20:00:00 2019-02-19 22:00:00 2019-02-19 22:00:00 2019-02-19T15:00:00-05:00 2019-02-19T17:00:00-05:00 America/New_York America/New_York datetime 2019-02-19 03:00:00 2019-02-19 05:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioE PhD Defense Presentation- Phillip Trusty]]> 27917 Advisor: Ajit Yoganathan, PhD (BME)

 

Committee:

John Oshinski, PhD (BME)

J Brandon Dixon, PhD (ME)

Timothy Slesnick  (Children's Healthcare of Atlanta)

Shriprasad Deshpande   (Children's National)

Mark Fogel (Children's Hospital of Philadelphia)

 

Hemodynamic Assessment of Proposed Solutions for Fontan Failure

 

Single ventricle heart defects are among the most severe types of congenital heart problems and require surgical intervention for survival. Thankfully, over the last 40 years surgeons have pioneered a set of 3 staged surgeries to palliate single ventricle heart defects, which results in a total cavopulmonary connection. Short term outcomes of these “Fontan” patients are very promising, with a 1 year survival rate around 95%. However, as these patients age, long term complications are inevitable. The central purpose of this thesis is to investigate the effectiveness of current, clinically implemented “solutions” for two of the most common modes of Fontan failure including pulmonary arteriovenous malformations (PAVMs) and liver disease.  Specific Aim 1 will test if surgical planning can be used to accurately predict post-operative hepatic flow distribution (a factor in PAVM formation), and if Y-grafts can provide more balanced hepatic flow distribution than traditional Fontan connections. Specific Aim 2 will test if the extent of liver fibrosis in Fontan patients is associated with poor hemodynamics, and if ventricular assist devices can decrease Fontan hepatic congestion by augmenting flow and decreasing inferior vena cava pressure.  

]]> Laura Paige 1 1547656813 2019-01-16 16:40:13 1547656813 2019-01-16 16:40:13 0 0 event BioE PhD Defense Presentation- "Hemodynamic Assessment of Proposed Solutions for Fontan Failure"- Phillip Trusty

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2019-02-04T12:00:00-05:00 2019-02-04T14:00:00-05:00 2019-02-04T14:00:00-05:00 2019-02-04 17:00:00 2019-02-04 19:00:00 2019-02-04 19:00:00 2019-02-04T12:00:00-05:00 2019-02-04T14:00:00-05:00 America/New_York America/New_York datetime 2019-02-04 12:00:00 2019-02-04 02:00:00 America/New_York America/New_York datetime <![CDATA[]]> Laura Paige

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<![CDATA[BioEngineering Graduate Committee Meeting]]> 27917 The BioEngineering graduate committee will meet to review/approve program policies, program faculty applications and submitted student petitions.

]]> Laura Paige 1 1547656240 2019-01-16 16:30:40 1547656240 2019-01-16 16:30:40 0 0 event BioEngineering Graduate Committee Meeting

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2019-01-22T10:00:00-05:00 2019-01-22T11:00:00-05:00 2019-01-22T11:00:00-05:00 2019-01-22 15:00:00 2019-01-22 16:00:00 2019-01-22 16:00:00 2019-01-22T10:00:00-05:00 2019-01-22T11:00:00-05:00 America/New_York America/New_York datetime 2019-01-22 10:00:00 2019-01-22 11:00:00 America/New_York America/New_York datetime <![CDATA[]]>