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| CELLULAR AND MOLECULAR MECHANISMS - PAST GRANTS |
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Massachusetts Institute of Technology, Cambridge , MA
2004-2008
Principal Investigator: Damon Page, Ph.D.
Toward an Understanding of the Developmental Basis of Brain Dysfunction in Autism: Molecular and Cellular Mechanisms of Cortical Region and Network Formation
The cerebral cortex is made up of anatomically and functionally distinct regions and past evidence has suggested that abnormal formation and activity of certain areas may be involved in autism. This research will investigate morphological and functional regionalization of the mammalian cerebral cortex in normally developing mouse models to understand how the development of the cerebral cortex may be disrupted in autism. The use of diverse tools available in mice will enable us to understand how genes cooperate with one another and with extrinsic signals to build regions and functional circuitry in the cerebral cortex. This research will provide a basis for understanding how processes may be disrupted in individuals with autism, and should contribute to better diagnosis and treatment of this condition.
Damon Page
Vanderbilt University, Nashville, TN
2007-2008
Principal Investigator: Pat Levitt, Ph.D.
MET Receptor Tyrosine Kinase and Autism Spectrum Disorders (Co-funded with the Simons Foundation)
MET is a protein that mediates cell functions involved in building brain architecture, and in gastrointestinal repair and immune responses. Based on their discovery of a variant of the MET gene that is associated with autism spectrum disorder (ASD), Dr. Levitt and colleagues hypothesize that alterations in MET function contribute to the brain-based and medical conditions that characterize individuals with ASD. They also hypothesize that environmental factors compound genetic risk by disrupting MET expression. The functional MET variant, which decreases expression of the gene approximately 2-fold, more than doubles the risk of ASD. The investigators will determine whether the variant defines individuals with specific medical and behavioral co-occurring conditions. Subjects with ASD and co-occurring medical conditions, such as GI or immune disorders will be studied through ASD medical clinics at Vanderbilt and Massachusetts General Hospital . The investigators will determine which individuals carry the ASD-associated MET variant, and correlate expression of the MET protein in blood immune cells and when available, in gut biopsies. These subjects and those from the AGRE and Simons collections will be subdivided using available behavioral and social scales to determine if the MET variant is found more prevalently with certain traits. Finally, the investigators will examine how the MET variant in cells responds following exposure to common environmental toxins, such as dioxin and fertilizers that interfere with gene expression. This research program will lead to better means for diagnosing and treating subgroups of ASD patients, and determine how gene-environment may play a role in increasing ASD risk.
Vanderbilt Kennedy Center for Research on Human Development
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