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George P. Christophi
MSIII
christog@upstate.edu
Department: Microbiology & Immunology
Advisor: Paul Massa, Ph.D.
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Research Interests:
Medical treatments are advancing to include biological therapies recently discovered following intense research. Although we know that Interferons, TNF-a, Type I & II Cytokines signal through receptors and signal transducer molecules like STATs, NF-kB, and kinases to exert an array cellular effects, we are far away from understanding the positive and negative effects they have on patients. In order to answer some of these questions, our lab focuses on extending research from the tissue culture room to mouse studies and all the way to the clinics. I study cytokine signaling pathways and how they affect gene transcription both in the immune system and in the CNS. SHP-1 is a protein phosphatase that negatively regulates several transcription factors and is important in hematopoiesis, anti-viral responses, and immune-mediated demyelination. We have recently discovered that multiple sclerosis patients are SHP-1 deficient leading to increased cytokine signaling and inflammatory gene expression. We are exited that we discovered treatments that raise the levels of SHP-1 and functionally reduce inflammatory cytokine signaling that can exacerbate disease pathogenesis.
Publications:
Christophi GP & Massa PT. 2010. Central Neuroinvasion and Demyelination by Inflammatory Macrophages Following Peripheral Virus Infection is Controlled by SHP-1. Viral Immunology:In Press
Christophi GP, Panos M, Hudson CA, Mihai C, Jubelt B, Massa PT. 2009 Interferon-b Treatment in Multiple Sclerosis Attenuates Inflammatory Gene Expression Through Inducible Activity of the Phosphatase SHP-1. Clinical Immunology: 6:24
Christophi GP, Panos M, Hudson CA, Blystone SD, Jubelt B, Massa PT. 2009. Macrophages of multiple sclerosis patients display deficient SHP-1 expression and enhanced inflammatory phenotype. Laboratory Investigation: April; 27 1-18
Christophi GP, Hudson CA, Panos M, Gruber R, Massa PT. 2009. Modulation of macrophage infiltration and inflammatory activity by the phosphatase SHP-1 in virus-induced demyelinating disease. Journal of Virology: Jan;83(2):522-39
Jubelt B, Movileanu I, West KS, Christophi GP, Massa PT, Acsadi AJ, Acsadi G. Retrograde Viral Delivery of GDNF and IGF1 Prevents the Development of Late Weakness (Post-Polio Syndrome) in a Mouse Model. Manuscript in preparation
Hudson CA, Christophi GP, Gruber RC, Lawrence DA, Massa PT.2008. Induction of IL-33 expression and activity in central nervous system glia. Journal of Leukocyte Biology: Sep;84(3):631-43
Christophi GP, Hudson CA, Gruber R, Christophi CP, Massa PT. 2008. Promoter-specific induction of the phosphatase SHP-1 by viral infection and cytokines in CNS glia. Journal of Neurochemistry: Apr; 105 (6):2511-23.
Hudson CA, Christophi GP, Cao L, Gruber RC, Massa PT. 2006. Regulation of avoidant behaviors and pain by the anti-inflammatory tyrosine phosphatase SHP-1. Neuron Glia Biology: Nov;2(4):235-246.
Christophi GP, Hudson CA, Gruber RC, Christophi CP, Mihai C, Mejico LJ, Jubelt B, Massa PT. 2008. SHP-1 deficiency and increased inflammatory gene expression in PBMCs of multiple sclerosis patients. Laboratory Investigation: Mar; 88 (3):243-55
Scarisbrick IA, Blaber SI, Rodriguez M, Blaber M, Christophi GP. 2006. Potential scope of action of tissue kallikreins in CNS immune-mediated disease. Journal of Neuroimmunology: Sep;178 (1-2):167-76.
Christophi GP, Isackson PJ, Blaber S, Blaber M, Rodriguez M, Scarisbrick IA. 2004. Distinct promoters regulate tissue-specific and differential expression of kallikrein 6 in CNS demyelinating disease. Journal of Neurochemistry: 91(6):1439-49.
Blaber SI, Ciric B, Christophi GP, Bernett MJ, Blaber M, Rodriguez M, Scarisbrick IA. 2004. Targeting kallikrein 6-proteolysis attenuates CNS inflammatory disease. FASEB Journal: 19, 920-922.
PRESENTATIONS:
Christophi GP & Massa PT. 2009. SHP-1 Reigns the Trojan Horse: Macrophage-mediated Virus Neuroinvasion in SHP-1-deficient mice. Internal Medicine 2009, APC Meeting, Philadelphia, PA
Christophi GP, Panos M, Hudson CA, and Massa PT. 2008.Modulation of macrophage infiltration and inflammatory activity by the phosphatase SHP-1 in virus-induced demyelinating disease. Conference of the International for Interferon and Cytokine Research. (Cytokine Journal ,September 2008 43:3)
Christophi GP, Jubelt B, and Massa PT. 2008. Interferon-b Treatment of Multiple Sclerosis Patients Induces SHP-1 Expression and Modulates Pro-inflammatory Gene Expression in PBMCs n vivo. Treatment and Research in Multiple Sclerosis. Montreal, Canada (Mult Scler Journal,2008; 14; S29)
Christophi GP, Jubelt B, Massa PT. 2007. Deficiency of SHP-1 and Increased Cytokine Signaling in Multiple Sclerosis Patients. Inflammation, Innate immunity, & Canser: Leukocyte Biology Society. Cambridge, MA.
Christophi GP, Hudson CA, and Massa PT. 2007. SHP-1 Promotes Type 1 Immune-Induced Paralytic Disease. Tri-Institutional MD/PhD Research Conference. Syracuse, NY.
Christophi GP, Christophi C, Hudson C, and Massa PT 2006. Increased Type 2 Innate Immunity & Virus Replication in SHP-1-Insufficient mice. American College of Physicians NY Chapter, Buffalo, NY.
Christophi GP, Hudson CA, and Massa PT. 2006. Increased Virus Replication in SHP-1-Insufficient mice. The 8th Annual Upstate New York Immunology Conference. Bolton Landing, NY.
Christophi GP and Scarisbrick IA. 2004. Tissue-Specific Expression and Differential Regulation of Multiple Kallikrein 6 Transcripts in CNS Demyelinating Disease. Society for Neuroscience. San Diego, CA. (Journal of Neuroscience. 2004, October: Supplement).
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