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Research: Specification of Neuronal Connectivity by Cell Recognition Molecules

Professor of Biochemistry and Biophysics
(PhD – University of Texas)

HONORS & AWARDS

  • Pogue Fellowship for Scholarly Research: 2012
  • Member NIH Neurodifferentiation, Plasticity, and Regeneration (NDPR) Study Section: 2013 – current
  • Distinguished Investigator Award, National Alliance for Research on Schizophrenia and Depression (NARSAD): 1999-2002
  • NIH Research Career Development Award: 1988-1992
  • Jefferson-Pilot Award in Academic Research: 1984

RESEARCH SUMMARY

How neuronal circuitry in the brain is established during development and refined in the adult is a central unanswered question in neuroscience. Neural recognition molecules expressed on the neuronal surface are pivotal players in developing cortical circuits. Among the most relevant of these molecules to human disease are members of the NCAM and L1 family (L1, CHL1, NrCAM, Neurofascin). Each of these cell recognition molecules has established functions in axon guidance that mediate correct topographic synaptic targeting of axons, while exciting new findings reveal that they also have vital functions in regulating synaptogenesis and plasticity of cortical networks. Importantly, mutations in neural adhesion molecule genes may contribute to susceptibility to human neuropsychiatric diseases such as schizophrenia, autism spectrum disorders, and intellectual disability. To study the normal and abnormal function of neural cell adhesion molecules in brain development and function, our laboratory uses a multidisciplinary approach to generate and analyze novel mouse genetic models of neurodevelopmental disorders. Neural adhesion molecules of the immunoglobulin superfamily (Ig-CAMs) are risk factors for neurodevelopmental disorders such as autism, schizophrenia, and intellectual disability. Maness transformed our understanding of how IgCAMs function by discovering that they are not molecular “glue” but are signaling receptors that establish and refine neuronal connectivity in the mammalian brain. Using novel mouse models she demonstrated that IgCAMs mediate topographic axon targeting and synaptogenesis, and identified their signaling pathways through Src, RhoA and MAP kinases. She was first to determine that a normal proto-oncogene product, c-Src, functions to regulate neuronal axon guidance, rather than proliferation, distinguishing it from its oncogenic counterpart. This finding had widespread implications for our understanding that proto-oncogenes play normal roles in cell differentiation.

PUBLICATIONS

Link to all PubMed publications

 

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