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CAREER DEVELOPMENT AWARDS - PAST GRANTS  
 

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


Massachusetts Institute of Technology, Cambridge , MA
2009-2010

Principal Investigator: Damon Page, Ph.D.

MAPK3 as a Chr 16p11.2 Autism Candidate Gene

he chromosomal region of 16p11.2 has emerged from genetic screening in humans as a significant susceptibility locus for ASD. This interval contains 25 genes; however, the link between these genes and the symptoms of ASD is not clear. Dr. Page’s research seeks to bridge this gap in our understanding by investigating the role of candidate genes from the 16p11.2 region in the development of brain and behavior, using the mouse as a model system. The first candidate gene he will focus on is MAPK3. Dr. Page selected this gene as a candidate for the following reasons: 1) He previously found that ERK, the Drosophila homologue of MAPK3, influences regionalized growth in the embryonic brain by controlling proliferation of specific populations of neural stem cells in response to activation of the receptor tyrosine kinase EGFR in these cells (Page, 2003), 2) MAPK3 is know to act in the PTEN/PI3K pathway to influence a variety of cellular processes relevant to growth (Cully et al., 2006). Dr. Page has found that haploinsufficiency for Pten leads to brain overgrowth as well as social behavioral deficits (Page et al., 2009), two phenotypes relevant to ASD. And, 3) MAPK3 acts in several additional pathways that have been implicated in ASD pathogenesis, including: Serotonin (Launay et al., 1996), Oxytocin (Blume et al., 2008) and IL-6/immune signaling (D'Arcangelo et al., 2000). Dr. Page’s studies indicate that Pten intersects with these pathways in the developing brain. Thus, the possibility that MAPK3 might act as an intermediary across these pathways is one worth exploring. As an initial investigation of the function of Mapk3 in ASD-relevant endophenotypes, Dr. Page will make use of assays of social approach behavior and brain growth.

Damon Page



 
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