neuro-phys

One of many research initiatives in assistant professor Rick Matthews' lab focuses on the role of extracellular matrix and cell surface glycoproteins in the developing nervous system and in learning, memory, plasticity and diseases. This slide shows extracellular matrix (ECM) staining on a glioma initiating cell.

Neuroscience Program Faculty

Brian Howell, PhD

Brian Howell, PhD
Appointed 10/01/08
4701 Institute For Human Performance
505 Irving Ave.
Syracuse, NY 13210

315 464-8154

Current Appointments

Hospital Campus

  • Downtown

Research Programs and Affiliations

  • Biomedical Sciences Program
  • Neuroscience Program
  • Neuroscience and Physiology
  • Physiology Program

Education & Fellowships

  • PhD: McGill University, Montreal, Quebec, 1992
  • BS: University of Western Ontario, Canada, 1985

Previous Appointments

  • NIH, Bethesda MD, 1999–2008

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.

Publications

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Research

Brain development is an exquisitely regulated phenomenon, whereby waves of differentiation produce diverse classes of neurons, oligodendrocytes and finally, astrocytes. Ultimately these cells, particularly the neurons, organize into functional networks that receive, integrate and transmit information. My lab studies how molecular signaling regulates the migration of neurons from their site of origin to destinations where they extend processes, form synapses and integrate into networks. One of our focuses is to investigate how the Reelin signaling pathway influences the positioning of distinct neuronal classes into stereotypical layers in the brain. Reelin, a secreted ligand, induces the tyrosine phosphorylation of the intracellular docking protein Dab1 by clustering the neuronal receptors ApoER2 and VLDLR and activating Src-family kinases. The tyrosine phosphorylation of Dab1 generates signaling complexes that includes the molecules Nckβ, Crk, CrkL and PI3K. These complexes regulate the behavior of neurons as they migrate, enabling them to settle into layers. We have shown that Reelin signaling influences the extension of the Golgi apparatus into neuronal dendrites and the ability of neurons to polarize. We are currently investigating how these cellular behaviors influence neuronal positioning and other neuronal properties regulated by Reelin signaling.

We have recently expanded our focus to include genetic causes of autism spectrum disorder (ASD); specifically RELN mutations, more than 40 of which have been identified in ASD patients. We have found that mutations are enriched in an Arg-X-Arg motif in the core of the Reelin subrepeat domains. The function of the paired Arg residues is unknown. Therefore, we are working to resolve the consequences of mutations in this motif in Reelin biosynthesis and signaling with the ultimate goal of determining how they contribute to ASD.

Selected Publications

1. Howell, B.W., Hawkes, R., Soriano, P., and Cooper, J.A. (1997). Neuronal position in the developing brain is regulated by mouse disabled. Nature, 389: 733-737.

2. Pramatarova, A., Ochalski, P.G., Lee, C-H., Howell, B.W. (2006) Mouse Disabled 1 regulates the nuclear position of neurons in a Drosophila eye model. Mol. Cell. Biol. 26:1510-1517.

3. Pramatarova, A., Chen, K.-L., Howell, B.W. (2008) A genetic interaction between the APP and Dab1 genes influences brain development. Mol. Cell. Neurosci.37:178-186.

4. Matsuki, T., Pramatarova, A., Howell B.W. (2008) Reduction of Crk and CrkL expression blocks Reelin-induced dendritogenesis. J. Cell Sci. 121:1869-1875.

5. Matsuki, T., Matthews, R.T., Cooper, J.A., van der Brug, M.P., Cookson, M.R., Hardy, J.A., Olson, E.C., Howell, B.W. (2010) Reelin and Stk25 have opposing roles in neuronal polarization and dendritic golgi deployment. Cell 143:826-836.

6. Matsuki, T., Zaka, M., Guerreiro, R., van der Brug, M.P., Cooper, J.A., Cookson, M.R., Hardy, J.A., Howell, B.W. (2012) Identification of stk25 as a genetic modifier of Tau phosphorylation in dab1-mutant mice. PLoS ONE 7(2): e31152.

7. Teixeira, C.M., Kron, M.M., Masachs, N., Zhang, H., Lagace, D.C. Martinez, A., Reillo, I., Duan, X., Bosch, C., Pujadas, L., Brunso, L., Song, H., Eisch, A.J., Borrell, V., Howell, B.W., Parent, J.M., Soriano, E. (2012) Cell-autonomous inactivation of the Reelin pathway impairs adult neurogenesis in the hippocampus. J. Neurosci. 32:12051-12065.

8. Matsuki, T., Chen, J., Howell, B.W. (2013) Acute inactivation of the serine-threonine kinase Stk25 disrupts neuronal migration. Neural Dev. 2013, 8:21 doi:10.1186/1749-8104-8-21.

9.Abadesco, A.D., Cilluffo, M., Yvone, G.M., Carpenter, E.M., Howell, B.W., and Phelps, P.E. (2014) Novel Disabled-1-expressing neurons identified in adult brain and spinal cord. Eur. J. Neurosci. 39:579-592.

10. Lammert, D.B., and Howell, B.W. (2016) RELN mutations in autism spectrum disorder. Front. Cell. Neurosci. 10:84 doi: 10.3389/fncel.2016.00084

 

Faculty Profile Shortcut: http://www.upstate.edu/faculty/howellb

Additional Collaborators

  • Paul Gold, PhD
    Professor, Biology (Syracuse University)
    Research Interests: Aging, Cell Signaling and Communication, Learning, Memory, and Plasticity, Neurological and Psychiatric Conditions.
  • James Hewett, PhD
    Associate Professor, Biology (Syracuse University)
    Research Interests: Neuroscience and Central Nervous System Neurobiology and Pathology: Neuromodulators and Epilepsy: Arachidonic Acid Metabolism and Cyclooxygenase-2: Cytokines and Interleukin-1beta: Signal Transduction and Gene Expression.
  • Sandra Hewett, PhD
    Professor, Neuroscience, Biology (Syracuse University)
    Research Interests: Mechanisms underlying cell death in the central nervous system: the interplay between excitotoxicity and inflammation.
  • Donna Korol, PhD
    Associate Professor, Biology (Syracuse University)
    Research Interests: Neural mechanisms of learning and memory across the lifespan.
  • Katharine (Kate) Lewis, PhD
    Associate Professor, Biology (Syracuse University)
    Research Interests: Specification and patterning of spinal cord interneurons; Formation of functional neuronal circuitry; Evolution of spinal cord patterning and function; Dorsal-ventral neural tube patterning; zebrafish development.