Faculty and Staff

Paul T Massa, Ph.D. Professor, Neurology 5816 University Hospital Upstate Medical University 750 East Adams Street Syracuse, NY 13210 (315) 464-7606 Lab/Professional Web Site

Education and Clinical Training

Research Program and Department Affiliations

Research Interests

Research Abstract

Regulation of innate immunity in the CNS by the protein tyrosine phosphatase SHP-1.

Pattern recognition receptors (PRRs) expressed on CNS cells detect multiple pathogen-associated molecular patterns (PAMPS) during infections within the CNS to promote innate inflammatory immune responses. Cytokines potentially expressed by CNS glia in response to particular PAMPs include interferons or interleukin-4/13 depending on the pathogen. Interferons stimulate anti-viral responses while interleukin-4/13 promotes allergy-related responses. We have found that the protein tyrosine phosphatase SHP-1 is a key regulator of signaling through PRRs, interferon receptors, and interleukin-4/13 receptors which we believe relates to severe virus-induced immunopathogenesis with the CNS of SHP-1-deficient mice. Our current goal is to determine the mechanism by which SHP-1 controls the biological activities of these receptors in cells of the CNS. These studies will be important in understanding pathogen-specific immunopathogeneses in the CNS.

Regulation of oligodendrocyte development by SHP-1

Mice lacking the protein tyrosine phosphatase SHP-1 display a marked reduction of myelin within the central nervous system. Recently, we discovered that SHP-1 was expressed in myelin-forming oligodendrocytes and controlled myelin gene expression in response to cytokines and growth factors. Our current goal is to discover how SHP-1 controls myelin gene expression at the transcriptional level in oligodendrocytes and how this regulation is important for normal myelination by terminally differentiated oligodendrocytes.

Regulation of cytokine responses in the CNS by interferon regulatory factor-1(IRF-1)

IRF-1 is a key transcription factor that integrates multiple signals generated by cytokines and cellular stress. IRF-1 acts to increase the expression of pro-inflammatory and pro-apoptotic genes in both virus infected and transformed cells thereby aiding in eradication of these cells. Likewise, IRF-1 increases expression of genes that promote inflammation during virus infections and metabolic stress in the central nervous system. However, because inflammation is generally damaging to CNS cells, especially neurons, we are interested in multiple mechanisms that modulate IRF-1 activity. Of particular interest is the unique regulation of NF-kappaB activation by canonical and translational pathways that modulate IRF-1 gene transcription in neurons. These studies are likely to be important for understanding mechanisms of neuroinflammatory disease that particularly affect CNS neurons in humans.

Selected References

Paul T. Massa, Stacie Ropka, Sucharita Saha, Karen Fecenko, and Kathryn Beuler. 2002 A critical role for protein tyrosine phosphatase SHP-1 in controlling infection and demyelination by Theiler's murine encephalomyelitis virus. J. Virol. 76: 8335-8346.

Paul T. Massa, Charlene Wu, and Karen Fecenko-Tacka. 2004 Dysmyelination and reduced myelin basic protein gene expression by oligodendrocytes of SHP-1-deficient mice. J. Neurosci. Res. 77: 15-25.

Bonaparte, K.L., Hudson, C., Wu, C. and Massa, P.T. 2006. Inverse regulation of inducible nitric oxide synthase (iNOS) and arginase I by the protein tyrosine phosphatase SHP-1 in CNS glia. Glia 53: 827-835.

Massa, P.T., Aleyasin, H., Park, D.S., Mao, X., Barger, S.W. 2006 NF-?B in neurons? The uncertainty principle in neurobiology. J. Neurochem. 97: 607-618.

Hudson, C.A., Christophi, G.P., Cao, L., Gruber, R.C., and Massa, P.T. 2006 Regulation of avoidant behaviors and pain by the anti-inflammatory tyrosine phosphatase SHP-1. Neuron Glia Biol. 2: 235-246.

Publications - link to PubMed

This profile was last updated on 09/29/2008

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