Phd Proposal by Angela Jimenez
BME PhD Proposal Presentation
Location / Meeting Link: Krone Engineered Biosystems Building Children's Healthcare of Atlanta Seminar Room (EBB CHOA) / https://emory.zoom.us/j/91087968985?pwd=Y01EQjViODdBOUhkTEJ2aGthdURMUT09
Krishnendu Roy, PhD (Advisor), Carolyn Yeago, PhD, Johnna Temenoff, PhD, Edward Botchwey, PhD, Rabin Tirouvanziam, PhD
Title: Longitudinal Non-Destructive Multi-Omics Monitoring during Mesenchymal Stromal Cell Manufacturing for Identification and Prediction of Immunomodulatory Properties in Acute Respiratory Distress Syndrome (ARDS)
The transition from traditional pharmacological drugs to cell therapies as living medicines has been highly explored in recent years. Cell therapies can originate from various sources in the body. However, they must undergo a series of processing including in vitro expansion to produce a therapeutic dose. As a result, the inherent variability existing between donors, cell sources, and expansion methods has yielded heterogeneous responses in a clinical setting. Within cell therapies, mesenchymal stromal cells (MSCs) have been clinically investigated for their anti-inflammatory and tissue repair capabilities, mediated by paracrine signaling and cell-cell contact. Yet, clinical translation is limited by non-standardized and complex manufacturing processes and a lack of well-defined critical quality attributes (CQAs). More specifically, there is a need to develop non-destructive analytical techniques to monitor and identify CQAs and critical process parameters (CPPs) during the cell manufacturing process to predict the therapeutic potency of MSCs. One disease where MSCs hold promise as a therapeutic is acute respiratory distress syndrome (ARDS), a chronic lung infection that can originate from direct lung damage, sepsis, severe pneumonia, or COVID-19. ARDS causes fluid buildup in the lungs, cell death, high levels of inflammation, and deprivation of air in the lungs, creating an immense systemic response as all tissues and organs fail to receive proper oxygenation for function. Therefore, this project aims to (i) develop analytical platforms to measure the metabolome and secretome of MSCs during the manufacturing process, correlate and predict MSC potency, and (ii) apply our findings to test the efficacy of MSC therapies in vitro and in a humanized murine ARDS model. This proposed project will work towards the production of high-quality, reproducible, and therapeutic MSCs that will help realize the potential of cell-based immunotherapies for the treatment of ARDS.