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Ting Zhou

Memorial Sloan Kettering Cancer Center, USA

Using human pluripotent stem cells as platform for disease investigation and drug discovery 

Human pluripotent stem cells (hPSCs) and the functional cells derived from them can be utilized for chemical screen, complex disease investigation and drug discovery. The first example I present today is to set up a novel hPSC-based platform to uncover potential gene-environment interactions. We have performed an environment chemical screen on hESC derived β-like cells, and found that a commonly used pesticide, propargite, induced pancreatic β-cell death, a pathological hallmark of diabetes which is impacted by both genetic and environmental factors.  We then assessed the potential gene-environment interactions using isogenic hPSC lines for genetic variants associated with diabetes, and found a that GSTT1−/− pancreatic β-like cells were hypersensitive to propargite-induced cell death. This study identified an environmental chemical that could contribute to human β-cell loss and validated the hPSC-based platform for determining gene-environment interactions. The second example is to utilize hPSC-derived neural progenitors to perform a high content screen for anti-ZIKV drug discovery. Using the platform, we have screened >1,000 FDA-approved drug candidates, and found two with anti-ZIKV activity: Hippeastrine hydrobromide (HH) and Amodiaquine dihydrochloride dihydrate (AQ). The drug candidates were further validated with hPSC-derived forebrain organoids in vitro and a murine model in vivo.

Biography

Dr. Ting Zhou is the Director of the Stem Cell Research Facility and an Assistant Lab Member in Memorial Sloan Kettering Cancer Center. She is an experienced stem cell biologist with great interest in the application of human pluripotent stem cell (hPSC) and genome editing technologies.