Terasaki Talks: Dr. Samuel Sances

“Replaying Human Neurophysiology and Disease with Microphysiological Systems and iPSC Technologies

Abstract: Neurodegenerative diseases of both familial and idiopathic origin are recognized as having genetic contributors that may present before birth. However, the identity of disease initiating genes and their contribution to cellular dysfunction leading to clinical presentation is poorly understood. Cedar-Sinai’s Tissue Chip team has developed two highly functional and scalable microphysiological models containing spinal cord cells (SC-Chip) to study sporadic ALS and midbrain cells (mBrain-Chip) to study sporadic Parkinson’s Disease. Both Chip models integrate a human microfluidic vascular channel that can interact with patient stem cell derived neural tissue and exhibit blood brain barrier properties. Cedars-Sinai’s Induced Pluripotent Stem Cell (iPSC) Core has generated large cohorts of patient and non-diseased iPSC lines for use in in vitro disease research and target discovery. The main objective of this work is to develop robust and reproducible human vascularized models of spinal cord and midbrain tissue, determine live and molecular signatures that indicate a diseased state, and test efficacy and blood brain barrier characteristics of candidate therapeutics. To determine disease Chip biomarkers, a comprehensive array of live and molecular assays were applied to Chip microtissues. These include whole genomic, transcriptomic, proteomic, metabolomic, and electrophysiological assays. Pilot disease cohorts of 10 patient lines were screened for candidate biomarkers in patient Chips using RNA-Seq, proteomics, calcium Imaging, and staining. Putative molecular biomarkers were identified as ALS and PD specific in the spinal cord Chip and midbrain Chip respectively.

Biography: Dr. Sances’ research focuses on utilization of patient derived stem cell-derived tissues and organ-on-chip systems to reproduce neurodegenerative diseases in vitro. He currently leads the tissue chip team under director Clive Svendsen Ph.D. at the Board of Governor’s Regenerative Medicine Institute at Cedars-Sinai Medical Center. Dr. Sances utilizes induced pluripotent stem cells (iPSC) to generate neurons and vasculature from patient cohorts. These cells are used to develop human specific brain- and spinal cord-chip models to discover new biomarkers of sporadic Parkinson’s disease and amyotrophic lateral sclerosis. His doctoral work on the maturation effects of vasculature on iPSC-derived motor neurons led him to develop human chip models that contain a human blood brain barrier and enable co-culture of multiple neurovascular and microglial cell types. His work in collaboration with other members of the Svendsen lab led to a recent landmark study using iPSCs to determine mechanistic insights and a potential treatment for young onset sporadic Parkinson’s disease. He began his work toward personalized medicine with a fellowship from the California Institute for Regenerative Medicine (CIRM) at Sanford-Burnham Medical Research Institute in La Jolla, CA and holds a doctorate in Biomedical Science and Translational Medicine from Cedars-Sinai Medical Center. His research has contributed to multiple grants funded through the National Institutes of Health and the ALS Association.

Event Information

Event Date 07-09-2020 8:00 am
Event End Date 07-09-2020 9:00 am
Registration Start Date 06-30-2020
Cut off date 07-09-2020 8:15 am

Our Locations

Follow Us