RESEARCH PROGRAMS AND AFFILIATIONS
Neuroimmunology: Regulation of genes involved in innate immunity and chronic inflammation in the CNS
Neurovirology: CNS-specific mechanisms involved in viral neurotropis, neuroinvasion, persistence, inflammation and anti-viral state.
Neurodegeneration: Neuron-specific regulation of apoptotic genes by NF-kappa B and mechanisms regulating CNS-specific mitochondrial bioenergetics.
ASSOCIATIONS / MEMBERSHIPS
Regulation of virus-induced innate immunity.
Pattern recognition receptors (PRRs) expressed on cells are important for detecting pathogen-associated molecular patterns (PAMPS) during virus infections and promoting innate inflammatory immune responses to the virus. While these responses are essential for eradication of a virus from the host, these responses may lead to extensive immunopathogenic tissue damage if not properly regulated. Among the myriad of proteins that regulate these responses in cells, the most critical is the protein tyrosine phosphatase SHP-1. As such, SHP-1 has been shown to be a key negative regulator of signaling intensiity through both PRRs and proinflammatory cytokine receptors expressed on cells. Our current goal is to determine the mechanisms by which SHP-1 appropriately controls the biological activities of these receptors during pathogen-induced inflammatory responses in various tissues and how these controls might be disrupted during severe inflammatory diseases particularly within the central nervous system.
Massa, P.T. and Wu, C. 1996 The role of protein tyrosine phosphatase SHP-1 in the regulation of IFN-γ signaling in neural cells. J. Immunol. 157:5139-5144.
Massa, P.T. and Wu, C. 1998 Increased inducible activation of NF-κB and responsive genes in astrocytes deficient in the protein tyrosine phosphatase SHP-1. J. Interferon and Cytokine Res. 18:499-507.
Massa, P.T., Whitney, L.W., Wu, C., Ropka, S.L., and Jarosinski, K.W. 1999 A mechanism for selective induction of 2’-5’ oligoadenylate synthetase, antiviral state, but not MHC class I genes by interferon-beta in neurons. J. Neurovirol.5:161-171.
Massa,P.T. , Saha, S., Wu,C., and Jarosinski,K.W. 2000 Expression and function of the protein tyrosine phosphatase SHP-1 in oligodendrocytes. GLIA 29:376-385.
Jarosinski,K.W., Whitney, L.W. And Massa, P.T. 2001 Specific deficiency in NF-κB activation in neurons of the central nervous system. Lab. Invest. 81:1275-1288.
Jarosinski,K.W. And Massa, P.T. 2002 Interferon regulatory factor-1 is required for interferon-γ-induced MHC class I genes in astrocytes J. Neuroimmunol.122:74-84.
Massa, P.T., Ropka, S., Saha, S., Fecenko, K. , and Beuler, K.. 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
Massa, P.T., Wu,C., and Fecenko-Tacka, K. 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-κB 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.
Christophi, G.P., Hudson, C.A., Gruber, R.C., Christophi, C.P., Mihai, C., Mehico, L.J., Jubelt, B., and Massa, P.T. 2008 SHP-1 deficiency and increased inflammatory gene expression in PBMCs of multiple sclerosis patients. Lab. Invest. 88: 243-255.
Christophi, G.P., Hudson, C.A., Gruber, R., Christophi, C.P., and Massa, P.T. 2008 Promoter-specific induction of the phosphatase SHP-1 by viral infection and cytokines in CNS glia. J. Neurochem.105: 2511-2523.
Hudson, C.A., Christophi, G.P., Gruber, R.C., Wilmore, J.R., Lawrence, D.A., and Massa, P.T. 2008 Induction of IL-33 expression and activity in central nervous system glia. J. Leuk. Biol. 84: 631-643.
Christophi, G.P., Hudson, C.A., Panos, M., Gruber, R.C. and Massa, P.T. 2009 Modulation of macrophage infiltration and inflammatory activity by the phosphatase SHP-1 in virus-induced demyelinating disease. J. Virol. 82: 522-539.
Christophi, G. P., M. Panos, C. A. Hudson, R.L. Christophi, R. C. Gruber, A. T. Mersich, S. D. Blystone, B. Jubelt, and P. T. Massa. 2009. Macrophages of multiple sclerosis patients display deficient SHP-1 expression and enhance inflammatory phenotype. Lab. Invest. 89: 742-759.
Christophi, G.P., Panos, M., Hudson, C.A., Tsikkou,C., Mihai, C., Mejico, L.J., Jubelt, B., Massa, P.T. 2009 Interferon–beta treatment in multiple sclerosis attenuates inflammatory gene expression through inducible activity of the phosphatase SHP-1. Clin. Immunol. 133: 27-44
Christophi, G.P. and Massa, P.T. 2009 Central neuroinvasion and demyelination by inflammatory macrophages following peripheral virus infection is controlled by SHP-1. Viral Immunol. 22: 371-387.
CHRISTOPHI, G. P., CHRISTOPHI, J. A., GRUBER, R. C., MIHAI, C., MEJICO, L. J., MASSA, P. T. & JUBELT, B. 2011. Quantitative differences in the immunomodulatory effects of Rebif and Avonex in IFN-beta 1a treated multiple sclerosis patients. J Neurol Sci, 307, 41-5.
CHRISTOPHI, G. P., GRUBER, R. C., PANOS, M., CHRISTOPHI, R. L., JUBELT, B. & MASSA, P. T. 2012. Interleukin-33 upregulation in peripheral leukocytes and CNS of multiple sclerosis patients. Clin Immunol, 142, 308-19.
KUMAGAI, C., KALMAN, B., MIDDLETON, F. A., VYSHKINA, T. & MASSA, P. T. 2012. Increased promoter methylation of the immune regulatory gene SHP-1 in leukocytes of multiple sclerosis subjects. J Neuroimmunol, 246, 51-7.
CHRISTOPHI, G.P., RONG, R., HOLTZAPPLE, P.G., MASSA, P.T., AND LANDAS, S.K. 2012 Immune markers and differential signaling networks in ulcerative colitis and Crohn’s disease. Inflamm. Bowel Dis. 18: 2342-2356.
CHRISTOPHI, G.P., CAZA, T., CURTISS, C., GUMBER, D., MASSA, P.T. AND LANDAS, S.K. 2014 Gene expression profiles in granuloma tissue reveal novel diagnostic markers in sarcoidosis. Exp. Mol. Pathol. 96: 393-399.
WATSON, N.B., SCHNEIDER, K. M., AND MASSA, P.T. 2015 SHP-1-dependent macrophage differentiation exacerbates virus-induced myositis. J. Immunol. 194: 2796-2809.
GRUBER, R.C., LAROCCA, D., MINCHENBERG, S.B., CHRISTIOPHI, G.P., HUDSON, C.A., RAY, A.K., SHAFIT-ZAGARDO, B., AND MASSA, P.T. 2015 The control of reactive oxygen species production by SHP-1 in oligodendrocytes. GLIA (In press).