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Pharmacogenetic Insights into the Treatment of Angelman Syndrome

Weekly Seminar
Who Should Attend: 


Guest Speaker
Ben Philpot, PhD
Kenan Distinguished Professor, Associate Director
UNC Neuroscience Center, Department of Cell Biology & Physiology
UNC School of Medicine, Chapel Hill, NC

Research Summary

Angelman syndrome is a severe neurodevelopmental disorder characterized by lack of speech, intellectual disability, and seizures. The disorder is caused by a loss of the maternal UBE3A allele; because the paternal allele is epigenetically silenced in neurons, loss of the maternal allele practically eliminates UBE3A protein from the brain. My lab strives to understand the basic pathophysiology underlying Angelman syndrome, and our research has provided synaptic and circuit insights into the basis for hyperexcitability in the Angelman syndrome brain. Simultaneous to our basic research studies, we have performed drug discovery that identified small molecules that can unsilence the paternal UBE3A allele and, hence, provide a treatment approach. Our research and that of others suggests that clinical trials are looming on the horizon. Given the increased interest in performing clinical trials, we have recently turned our attention towards identifying potential biomarkers in Angelman syndrome, including EEG recordings and MRI-DTI measurements of white matter integrity. In this talk, I will provide an overview of our understanding of Angelman syndrome pathophysiology and possible outcome measures that might be used in upcoming clinical trials.

Ben Philpot, Ph.D. Figure


Judson MC, Wallace ML, Sidorov MS, Burette AC, Gu B, van Woerden GM, King IF, Han JE, Zylka MJ, Elgersma Y, Weinberg RJ, Philpot BD.
GABAergic Neuron-Specific Loss of Ube3a Causes Angelman Syndrome-Like EEG Abnormalities and Enhances Seizure Susceptibility.
Neuron. 2016 Apr 6;90(1):56-69. doi: 10.1016/j.neuron.2016.02.040.
Huang HS, Allen JA, Mabb AM, King IF, Miriyala J, Taylor-Blake B, Sciaky N, Dutton JW Jr, Lee HM, Chen X, Jin J, Bridges AS, Zylka MJ, Roth BL, Philpot BD.
Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons.
Nature. 2011 Dec 21;481(7380):185-9. doi: 10.1038/nature10726.
Berrios J, Stamatakis AM, Kantak PA, McElligott ZA, Judson MC, Aita M, Rougie M, Stuber GD, Philpot BD.
Loss of UBE3A from TH-expressing neurons suppresses GABA co-release and enhances VTA-NAc optical self-stimulation.
Nat Commun. 2016 Feb 12;7:10702. doi: 10.1038/ncomms10702.


Tuesday, April 25, 2017 - 12:30pm


Burke Medical Research Institute
785 Mamaroneck Avenue
White Plains, NY 10605
United States
Conference Room: 
Billings Building – Rosedale

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