BI Seminar Series – Human Pluripotent Stem Cell Modeling of Genetic Epilepsies

Dr. Jack Parent is a Professor of Neurology, Director of the Neurodevelopment and Regeneration Laboratory and Co-director of the Comprehensive Epilepsy Center.

Reprogramming somatic cells to a pluripotent state via the induced pluripotent stem cell (iPSC) method offers an unparalleled approach for neurological disease modeling using patient-derived cells. I describe our application of the iPSC approach to model severe pediatric genetic epilepsies with patient-derived cells. Our 2-D iPSC culture studies of SCN1A-linked Dravet Syndrome show altered sodium currents and excitability in both iPSC-derived neurons and cardiomyocytes. Human embryonic stem cell or iPSC-derived cerebral organoid modeling of genetic epilepsies is described in the second part of the talk, including mTOR pathway and other non-ion channel epilepsies. Our findings suggest that patient-derived cell models are useful for understanding genetic epilepsy mechanisms and offer a strategy towards precision therapies.