Dr. Brown’s research laboratory is involved in elucidating the role of TNF family members in the development of graft-versus-host disease (GVHD). Specifically, her research focuses on the exploration of the relationship between immuno-modulators such as TNF inhibitors, and histopathology, pathogenic T cell’s activation and differentiation and pathophysiology of intestinal and hepatic GVHD. Her published data have confirmed that TNF blockade is associated with a decrease in the severity of intestinal inflammatory processes and a reduction in the increased colonic mucosal permeability and diarrhea that are hallmarks of murine GVHD. Her research has demonstrated that TNF is not only important in innate immune responses and host cell destruction during GVHD, but also is critical in development of the intense intestinal inflammation characteristic of a T cell mediated intestinal inflammatory disease. Furthermore, TNF and its family members appear to influence gut GVHD by polarization of the pathogenic T cells toward a pro-inflammatory T helper 1 (Th1) cytokine profile (IL-2, IFN?). Importantly, TNF and its family members also appear to be important in the development of the histopathology of hepatic GVHD (endothelialitis, bile duct and hepatocyte destruction). Currently Dr. Brown’s laboratory is determining the role of TNF/TNFR2, LTaa2/LTaR and/or LIGHT/HVEM interactions during the development of GVHD, specifically examining pathogenic cellular processes in both the intestine and the liver.
RESEARCH INTERESTS
Pathophysiology of inflammatory diseases
Murine intestinal graft-versus-host disease
RECENT PUBLICATIONS
Getachew Y, Browning J, Prebis M, Rogers T, Brown GR, "Combination therapy for the treatment of hepatitis C in the veteran population: higher than expected rates of therapy discontinuation" Alimentary Pharm and Therapeutics, 20:629-636, 2004
Brown GR, Lee E, and Thiele DL, "TNF/TNFR2 interactions are critical for the development of intestinal GVHD in MHC class II disparate (C57BL6J-C57BL/67 X bm12) F1 mice" Journal of Immunology, 6:3065-3071, 2002
Brown, GR, Lee, EL and Thiele, DL, "TNF enhances CD4(+) T cell alloproliferation, IFN-gamma responses, and intestinal graft-versus-host disease by IL-12-independent mechanisms" J Immunol, 170:5082-5088, 2003
Getachew Y, Browning J, Prebis M, Rogers T, Brown GR, "Combination therapy for the treatment of hepatitis C in the veteran population: higher than expected rates of therapy discontinuation" Alimentary Pharm and Therapeutics, 20:629-636, 2004
Brown GR, Lee EL, El-Hayek, Kintner K, Luck C, "IL-12-independent LIGHT signaling enhances MHC class II disparate CD4+ T cell alloproliferation, IFN-gamma response, and intestinal graft-versus-host disease." J Immunology., 174:4688-4695, 2005
El-Hayek, JM, Rogers T and Brown GR., "Tumor necrosis factor inhibition reduces MHC class I disparate murine liver GVHD." J Leukocyte Biology, 78:1001-1007, 2005
SIGNIFICANT PUBLICATIONS
Brown GR, Silva MD, Thompson PA, Beutler B, "Lymphoid hyperplasia, CD45RBhigh to CD45RBlow T-cell imbalance, and suppression of type 1 diabetes mellitus result from TNF blockade in NOD-NOD-scid adoptive T cell transfer" Diabetologia, 41:1502-1510, 1998
Brown GR, Thiele DL, Silva M, Beutler B, "Adenoviral vectors given intravenously to immunocompromised mice yield stable transduction of the colonic epithelium" Gastroenterology, 112:1586-1594, 1997
Brown GR, Lindberg, G, Meddings J, Silva M, Beutler B and Thiele DL, "Tumor necrosis factor inhibitor ameliorates murine intestinal graft-versus-host disease" Gastroenterology, 116:593-601, 1999
Brown GR and Thiele DL, "Enhancement of MHC class I-stimulated alloresponses by TNF/TNF receptor (TNFR)1 interactions and of MHC class II-stimulated alloresponses by TNF/TNFR2 interactions" Eur J Immuno, l30:2900-2907, 2000
Brown, GR Lee E and Thiele, DL, "TNF/TNFR2 interactions are critical for the development of intestinal graft-versus-host-disease in MHC class II-disparate (C57BL6J-C57BL/67 X bm12) F1 mice" J Immunol, 6:3065-3071, 2002
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