Science and Mathematics

CANCELED: Biology Faculty Candidate: Neuro-developmental Modeling of Cortical Malformations in Human Pediatric Epilepsy

April 6, 2020 at 12:00pm1:00pm

Life Sciences Complex, 106

Lakshmi Subramanian, Ph.D., from University of California San Francisco, is a candidate for a faculty position in the Department of Biology, part of the cluster hiring initiative in the BioInspired Institute. This hire is for the Brain Organoids position who will be a member of the Mechanics of Disease & Development focus group within BioInspired.

TITLE: Neuro-developmental Modeling of Cortical Malformations in Human Pediatric Epilepsy

ABSTRACT: Outer radial glial (oRG) cells are a population of neural stem cells prevalent in the developing human cortex that significantly contribute to its cellular diversity and evolutionary expansion. The mammalian Target of Rapamycin (mTOR) signaling pathway is active in human oRG cells. Mutations in mTOR pathway genes are linked to a variety of neurodevelopmental disorders and malformations of cortical development. I will discuss how dysregulation of mTOR signaling during development specifically affects oRG cells, but not other progenitor types, by changing the actin cytoskeleton through the activity of the small GTPase, CDC42. These effects change oRG cellular morphology, migration, and mitotic behavior. mTOR signaling thus acts as a regulator of cortical architecture by maintaining the cytoskeletal organization of oRG cells and the radial glia scaffold, providing insight into how mTOR dysregulation may contribute to neurodevelopmental disease. Patients with mTOR mediated malformations of cortical development have a disorganized cortex characterized by neurons of abnormal morphology, defects in cortical layering and intractable epilepsy. In surgical resections from these patients, abnormal neurons strongly express markers associated with oRG cells. Single nucleus sequencing of patient surgical resections confirms the distinct transcriptomic identity of these aberrant neurons, supporting their anomalous neuro-developmental origins. I will discuss how this finding has improved our ability to generate new models of the aberrant cellular and molecular changes that give rise to abnormal brain structures and neurodevelopmental disease.

HOST: Dr. Jessica MacDonald

Dr. Subramanian’s Chalk Talk is Tuesday, April 7, from 11:30 am-12:30 pm in Room 106 LSC.

Refreshments will be served at both events.

This event was first published on March 10, 2020 and last updated on March 19, 2020.


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