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A Tale of Two Families: Neural Precursor Cells from Idiopathic Autism Patients Exhibit Proliferation Phenotypes

by
Madeline Elaine Williams
B.S., Virginia Tech - 2012

Thesis Advisor: Emanuel DiCicco-Bloom, M.D.
Graduate Program in Neuroscience

CABM, Room 010
Piscataway

Tuesday, November 7, 2017
1:00 p.m.


Abstract

Autism spectrum disorder (ASD) is a highly complex, heterogeneous neurodevelopmental disorder characterized by an impairment in social communication and interaction as well as stereotyped/repetitive behavior. While ASD is a highly prevalent disorder (1:68), the underlying molecular mechanisms have yet to be identified and no therapeutics to treat core symptoms exist. As the name suggests, individuals with ASD have a wide range of severity of symptoms, intelligence levels, comorbid disorders, environmental and genetic contributions, different potential etiologies, and pathologies. This human social disorder characterized by vast heterogeneity cannot be properly modelled in a mouse, a challenge that has hindered the study of ASD. Here, I present methods for examining proliferation in human NPCs as well as a case study on two families examining ASD NPC proliferation in comparison to their sex-matched sibling controls. In comparison to their siblings, ASD patients present patient-specific proliferation phenotypes at baseline, in response to growth factors, and under environmental stressor conditions. A common phenotype emerges after exposure to methyl mercury (MeHg), both ASD patients show a reduction in sensitivity to the negative impact on DNA synthesis. In aggregate, I have created a toolset to measure patient-derived NPC proliferation, applied it to examine differences in ASD-sibling pairs, and identified both patient-specific and common patient phenotypes.


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