Skip to content

VCR's Distinguished Lecture Series

The VCR's Distinguished Lecture Series was created in an effort to educate and help the research community stay abreast on the world’s most pressing research topics.

During each of their visits, invited lecturers will meet with UTHSC administration, faculty and staff to share ideas and foster collaborative efforts centered on education, research and entrepreneurial ventures. They will also deliver a scientific lecture to the UTHSC community.

"Advancing a CRISPR / Cas gene therapy for Angelman Syndrome"

Presented by Mark Zylka, PhD, W.R. Kenan, Jr. Distinguished Professor in the Department of Cell Biology & Physiology and Director of the Neuroscience Center at The University of North Carolina at Chapel Hill on October 17, 2019 at 12:00 pm in the Freeman Auditorium (930 Madison Ave., 3rd Floor)

There is currently no effective treatment or cure for Angelman syndrome.  This severe neurodevelopmental disorder is caused by deletion or mutation of the maternally-inherited UBE3Aallele. These pathogenic mutations lead to loss of maternal UBE3A expression in neurons. The paternal UBE3Agene is silenced by an antisense transcript. CRISPR/Cas9 can be used to block expression of this antisense transcript and reactivate the paternal UBE3A gene in mouse and human neurons.  When delivered via an adeno-associated virus (AAV) gene therapy vector, this CRISPR/Cas9-based therapeutic can enduring reactivate UBE3A throughout the brain of mice.

Preclinical studies indicate that treating during the prenatal period could greatly reduce the severity of symptoms or prevent AS from developing.  New, highly sensitive non-invasive prenatal tests that take advantage of single cell genome sequencing technologies are expected to enter the clinic in the coming years and make early genetic diagnosis of AS more common. While prenatal therapies are currently not available for AS, prenatal testing combined with prenatal treatment has the potential to revolutionize how clinicians detect and treat babies before they are symptomatic.  This pioneering CRISPR/Cas gene therapy has the potential to be a first-in-class treatment for AS and lay the foundation for treating other syndromic neurodevelopmental disorders. 

About Dr. Zylka

Mark Zylka, Ph.D, was named Director of the UNC Neuroscience Center in 2016, and is responsible for hiring new faculty, shaping the direction of the Center, and for promoting neuroscience research campus-wide. After joining the faculty at UNC, he received several prestigious young investigator awards, including a Searle scholar award, a Sloan Foundation fellowship, a Klingenstein fellowship, Whitehall Fellowship, and Rita Allen fellowship. Dr. Zylka's lab has been continuously funded by the NIH, and receivied an NIH Pioneer award in 2013. His lab is broadly focused on developing novel treatments for chronic pain and autism. Specific projects in the lab include use of single-cell sequencing to study the normal and diseased brain, using machine learning approaches to assess pain in animal models, studying the role of topoisomerase 1 in the nervous system, developing a novel CRISPR/Cas9-based treatment for Angelman syndrome, and studying genetic and environmental risks for autism.

Dr. Zylka received his B.S. in Biochemistry from Virginia Tech. As an undergraduate, he was named a Barry Goldwater National scholar and he spent three summers at the NIH as an IRTA student. He completed his Ph.D. in Neurobiology from Harvard under the mentorship of Dr. Steven Reppert. While in graduate school, he identified several of the core circadian “clock” genes and determined at a mechanistic level how these genes contribute to circadian rhythms in mammals. He then did his postdoctoral work at Caltech and co-discovered a large family of G protein-coupled receptors called Mas-related genes (Mrgprs) that are exclusively found in sensory neurons of rodents and humans. These receptors are now being studied as therapeutic targets for pain and itch.

To see an archive of past presentations, please see the Recorded Lectures webpage.

Last Published: Oct 9, 2019