Faculty
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Brian Howell, Ph.D.
Assistant Professor, Neuroscience and Physiology
3235A Weiskotten Hall
Upstate Medical University
750 East Adams Street
Syracuse, NY 13210
315-464-8154
| Education and Clinical Training
BS: 1985, University of Western Ontario, Canada
Ph.D.: 1992, McGill University, Canada
Research Program and Department Affiliations
Biomedical Sciences Program
Research Interests The signal transduction events that regulate the functional organization of neurons in the brain, and the phenotypes caused by defects in the genes that encode these signaling molecules.
Research Abstract
My lab is focused on the molecular and cellular control of neuronal migration. We have a longstanding interest in the genes that encode the Reelin signaling pathway proteins. These include Reelin, a secreted ligand; the Reelin receptors, ApoER2 and VLDLR; the intracellular docking protein Dab1; and the Src-family kinases (SFKs). Reelin clusters the receptors on migrating neurons resulting in the activation of SFKs and Dab1 tyrosine phosphorylation. We have been investigating events downstream of Dab1 phosphorylation and have identified a number of phosphotyrosine-dependent Dab1 binding proteins, including Nckbeta, Crk and CrkL. We are working to understand the cellular consequences of the formation of Dab1 phosphotyrosine-dependent complexes.
One of our recent focuses is to identify genetic modifiers of the Reelin signaling pathway that participate in Tau phosphorylation. Tau is hyperphosphorylated in Alzheimer’s and other neurological diseases and leads to the formation of neurofibrillary tangles and neuron cell death. In Reelin pathway mutants, Tau phosphorylation is observed in a mouse strain-dependent manner. We have recently identified a gene that regulates Tau phosphorylation in Dab1 mutant mice and are working to characterize its role in brain development. Dab1 functionally interacts with the amyloid precursor protein (APP), which is involved in the early stages of Alzheimer’s disease. It will therefore be interesting to determine if the components of the Reelin-signaling pathway have implications for the initiation or progression of phenotypes associated with the development of Alzheimer’s disease.
Publications - link to PubMed
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This profile was last updated on 11/19/2008
A short link is available for this profile:
http://www.upstate.edu/neurophys/faculty.php?ID=howellb
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