University of Connecticut

Events Calendar

Neuroscience Seminar Series - Jack Parent

Tuesday, April 26, 2016
4:00pm – 5:00pm

UConn Health
Low Learning Center

Sponsored by CURE, Citizens United for Research, in Epilepsy - Frontiers in Research Seminar Series

Jack Parent, MD Professor of Neurology, Director, Neurodevelopment and Regeneration Laboratory, Co-Director, Comprehensive Epilepsy Center, University of Michigan Health System, Ann Arbor, MI

Title: "Induced Pluripotent Stem Cell Modeling of Genetic Epileptic Encephalopathies"

Abstract: 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 neurons. My lab has applied the iPSC approach to model severe childhood genetic epilepsies with patient-derived cells. We initially generated patient-derived neurons to study epilepsy mechanisms in Dravet Syndrome (DS), a catastrophic childhood epilepsy caused by de novo dominant mutations in the SCN1A gene that encodes the voltage-gated sodium channel Nav1.1. The talk will describe our findings of altered sodium currents and excitability in DS patient neurons. I will also discuss studies in which we generated DS patient-derived cardiac myocytes to explore potential mechanisms of SUDEP (Sudden Unexpected Death in Epilepsy), which occurs at increased frequency in DS. We compared findings from electrophysiological recordings of DS iPSC-derived cardiac myocytes with those of cardiac myocytes from a DS knock-in mouse model. In the last part of the seminar, I will describe recent work examining potential epilepsy mechanisms in another ion channelopathy, the severe childhood epilepsy known as SCN8A-Associated Epilepsy. Compared to control iPSC neurons, mutant SCN8A patient-derived neurons show increased persistent sodium current and hyperexcitability. Using a multi-well multielectrode array for drug screening, we are validating the model with drugs known to work or to be ineffective in patients with SCN8A-Associated Epilepsy. Taken together, our work suggests that the iPSC approach offers great promise for modeling childhood epileptic encephalopathies and should provide a useful platform to identify novel therapies.

CURE (Citizens United for Research in Epilepsy) is a 501(c)3 dedicated to finding a cure for epilepsy (http://www.CUREepilepsy.org).

Contact:

Jody Gridley, gridley@uchc.edu, 860-679-8787

Neuroscience Department at UConn Health (primary), Physiology & Neurobiology, UConn Health Master Calendar, UConn Master Calendar

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