{"582793":{"#nid":"582793","#data":{"type":"event","title":"BioE PhD Defense Announcement- Sangeetha Srinivasan","body":[{"value":"\u003Cp\u003E\u003Cstrong\u003EAdvisor\u003C\/strong\u003E: Julia E. Babensee,\u0026nbsp;PhD (Georgia Institute of Technology)\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ECommittee Members\u003C\/strong\u003E:\u003C\/p\u003E\r\n\r\n\u003Cp\u003EJulie A. Champion,\u0026nbsp;PhD (Georgia Institute of Technology)\u003C\/p\u003E\r\n\r\n\u003Cp\u003ESusan N. Thomas,\u0026nbsp;PhD (Georgia Institute of Technology)\u003C\/p\u003E\r\n\r\n\u003Cp\u003EEdward A. Botchwey,\u0026nbsp;PhD (Georgia Institute of Technology)\u003C\/p\u003E\r\n\r\n\u003Cp\u003EKrishnendu Roy, PhD (Georgia Institute of Technology)\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EConditioning Dendritic Cell Responses using Engineered Biomaterials for Immunotherapy\u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EPivotal discoveries in the field of immunology over the last five decades have changed the way new therapies are designed for applications as varied as organ transplantation, autoimmune diseases or even cancer. In this regard, dendritic cells (DCs) were identified to play an important role in the orchestration of adaptive immune response. Importantly, the phenotype of DCs is a powerful indicator of their downstream effector functions. In the recent years, parallel advancements made in biomaterial design and biocompatibility considerations are being directly translated into developing improved immunotherapies. Interestingly, biomaterials also elicit differential effects on the host immune response as well as on the phenotypic state of DCs.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;The first objective of this doctoral thesis was to validate the role of DCs in the previously documented \u003Cem\u003Ein vivo\u003C\/em\u003E PLGA adjuvant effect in boosting a humoral immune response to co-delivered antigen. Herein, by conditionally ablating DCs in a murine CD11c-DTR model, the adjuvant effect of PLGA towards co-delivered OVA was revisited. The diminished proliferation of adoptively transferred OVA-reactive T-cells in these mice was suggestive of a lowered adjuvant effect due to the absence of CD11c+ DCs. The second objective of this thesis was to design, develop and validate a multicomponent, multifunctional immunomodulatory (MI) scaffold comprised of macroporous agarose as the base scaffold material into which were embedded crosslinked gelatin microparticles (MPs), pre-loaded with immunomodulators, for their controlled release to mimic tolerogenic human or murine DC culture conditions. Aided by empirical modeling, using the Weibull equation, of experimental data using \u0026lsquo;model\u0026rsquo; proteins, we identified parameters of gelatin MP crosslinking density and number of embedded MPs in agarose to achieve prescribed temporal controlled release of immunomodulators for induction of tolerogenic DCs.\u0026nbsp; The prescribed MI scaffold aimed to release granulocyte monocyte colony-stimulating factor (GM-CSF; delivered within 0-3 days) to induce differentiation of monocyte precursors into DCs after dexamethasone (DEX, delivered within 3-6 days) addition would induce regulatory properties to these cells as well as peptidoglycan (PGN, delivered on days 5-6) to induce an alternative activated phenotype in DCs.\u0026nbsp; Such alternatively activated DCs (aaDCs), are endowed with immunosuppressive as well as directed lymph node migratory properties to effectively exert their tolerogenic effect.\u0026nbsp; Ability of this MI scaffold to induce tolerogenic phenotype in human blood-derived as well as murine bone marrow-derived cells was demonstrated upon \u003Cem\u003Ein vitro\u003C\/em\u003E treatment using a large cadre of immunological assessments.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EIn summary, this thesis documents the importance of DCs in the biomaterial adjuvant effect \u003Cem\u003Ein vivo\u003C\/em\u003E and provides a construct formulation that can be used to generate aaDCs with tolerogenic and migratory properties that are highly relevant in designing future immunotherapies targeting autoimmune diseases as well as in alleviating allograft rejection.\u003C\/p\u003E\r\n","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003EPhD Defense Presentation- \u0026nbsp;\u0026quot;Conditioning Dendritic Cell Responses using Engineered Biomaterials for Immunotherapy\u0026quot;- Sangeetha Srinivasan\u003C\/p\u003E\r\n","format":"limited_html"}],"field_summary_sentence":[{"value":"\u0022Conditioning Dendritic Cell Responses using Engineered Biomaterials for Immunotherapy\u0022"}],"uid":"27917","created_gmt":"2016-10-19 14:34:34","changed_gmt":"2017-04-13 21:14:15","author":"Laura Paige","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2016-11-01T15:00:00-04:00","event_time_end":"2016-11-01T17:00:00-04:00","event_time_end_last":"2016-11-01T17:00:00-04:00","gmt_time_start":"2016-11-01 19:00:00","gmt_time_end":"2016-11-01 21:00:00","gmt_time_end_last":"2016-11-01 21:00:00","rrule":null,"timezone":"America\/New_York"},"extras":[],"groups":[{"id":"65448","name":"Bioengineering Graduate Program"}],"categories":[],"keywords":[],"core_research_areas":[],"news_room_topics":[],"event_categories":[{"id":"1788","name":"Other\/Miscellaneous"}],"invited_audience":[{"id":"78761","name":"Faculty\/Staff"},{"id":"78751","name":"Undergraduate students"},{"id":"174045","name":"Graduate students"}],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003ELaura Paige\u003C\/p\u003E\r\n\r\n\u003Cp\u003E404.385.6655\u003C\/p\u003E\r\n","format":"limited_html"}],"email":[],"slides":[],"orientation":[],"userdata":""}}}