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John D. Wiley Seminar Series

Date: May 18, 2012

Time: Noon to 1:00 pm

Title: "Looking at Autism Through a Neurobiological Lens"

Speaker: Pat Levitt, PhD
Director, Zilkha Neurogenetic Institute
Provost Professor of Neuroscience, Psychiatry, Psychology & Pharmacy
Chair, Department of Cell and Neurobiology, Provost Professor of Neuroscience, Pediatrics, Psychology, Psychiatry and Pharmacy
Keck School of Medicine of USC
Provost Professor of Neuroscience, Pediatrics, Psychology, Psychiatry and Pharmacy

About the Talk: A significant challenge in improving the clinical manifestations of autism spectrum disorder (ASD) has been to place descriptive genetic findings in a functional context. Our overall goal is to determine the underlying cellular and molecular disruptions that lead to cognitive and behavioral phenotypes, and the factors that contribute to spectrum heterogeneity. Rare mutations generally have large effect sizes in altering causative phenotypes. Common polymorphisms typically have very small effect sizes for increasing ASD risk. However, when variants are shown to be functional, for example affecting gene transcription or protein function, their impact on altering specific neurobiological phenotypes relevant to ASD risk can be very substantial. The MET receptor tyrosine kinase is an illustration of this concept, having a 5' promoter variant that is associated with a small increase in ASD risk, yet has a large effect on gene transcription. Studies on the biological significance of regulationg MET expression in the brain have focused on its participation as a newly described synapse-associated receptor tyrosine kinase that regulates axonal and dendritic growth, spine, and synapse maturation. Phenocopying the ASD-related reduction of Met expression in heterozygous or homozygous null mice leads to hyperconnectivity of excitatory local circuits in the cortex. The large impact on specific phenotypes also is evident in humans, reflected in a remarkable change in gene expression patterning in the neocortex; there is an extreme enrichment of MET expression in regions of temporal and occipital areas in the primate that are involved in processing of complex visual stimuli, such as faces. Four lines of evidence in human neuroimaging studies demonstrate a potent correlation of the 'C' allele with atypical network activation and circuit structure. The convergent genetic, human functional and neurobiological data suggest that Met is involved in cellular pathogenic mechanisms, contributing to ASD risk and disorder heterogeneity.

About the Speaker: Dr Levitt received his undergraduate degree from the University of Chicago and the PhD degree in Neuroscience at the University of California, San Diego. He completed a postdoctoral fellowship in Neuroscience at Yale University. Dr. Levitt has held leadership positions at several medical schools, including Associate Dean of Graduate Studies at the Medical College of Pennsylvania, Chairman of the Department of Neurobiology at the University of Pittsburgh School of Medicine and Director of the Vanderbilt Kennedy Center for Research on Human Development. Named a McKnight Foundation Scholar in 2002, Dr. Levitt also was a MERIT awardee from the National Institute of Mental Health and recently completed his term as a member of the National Advisory Mental Health Council for the National Institute of Mental Health. He is an elected Fellow of the American Association for the Advancement of Science (AAAS), and the Dana Alliance for Brain Initiatives. He serves as Scientific Director of the National Scientific Council on the Developing Child and Director of the Marino Autism Research Institute. He is a member of a number of scientific advisory boards for foundations and university programs, and also is a member of six editorial boards of basic and clinical neuroscience journals. Dr. Levitt's research focuses on the development of brain architecture that controls learning, emotional and social behavior. His human genetics and basic research studies focus on understanding the causes of neurodevelopmental and neuropsychiatric disorders, such as autism and schizophrenia, and how genes and the environment together influence typical and atypical development. He has published over 225 scientific papers. Dr. Levitt is a frequently invited speaker at national and international scientific seminars and conferences. He also is an avid participant in business and policy forums that promote investments in the health and education of brain and child development. Dr. Levitt presents to state legislatures and to business groups, and in 2007, he spoke at the Summit on America's Children for House Majority Leader Nancy Pelosi.

Where: John D. Wiley Conference Center, Room T216, Second Floor, North Tower

For Further Information: Contact Teresa Palumbo at 263-5837 or palumbo@waisman.wisc.edu

This Seminar Series is partially funded by the John D. Wiley Conference Center Fund, the Friends of the Waisman Center and NIH grant P30 HD003352.