Our Research
Gerald T. Nepom, MD, PhD
Title:
Director of BRI, Director of Immune Tolerance Network
Email Address:
Phone Number:
(206) 342-6516
Background
Dr. Nepom received his bachelor’s degree in Biochemistry from Harvard in 1972 and doctorates from the University of Washington, receiving his PhD in Biochemistry in 1977 and his MD in 1978. After post-doctoral work in immunogenetics in the Department of Pathology at Harvard Medical School, he returned to Seattle, joining the Fred Hutchinson Cancer Research Center and the University of Washington Medical School Faculty in 1982. Since 1985 he has been Member and Director of the Benaroya Research Institute at Virginia Mason. In 2010, Dr. Nepom also became Director of the Immune Tolerance Network (ITN), sponsored by the National Institute of Allergy and Infectious Diseases (NIAID).
Areas of Research
Dr. Nepom's interests are focused on identifying and understanding molecular and genetic mechanisms contributing to pathogenesis of autoimmune disorders and using this information to evaluate autoreactive T cell lineage and fate determination. Translational and clinical applications include development and use of immunological monitoring tools for predicting disease susceptibility and response to therapy in clinical trials, with special emphasis on type 1 diabetes.
Selected Publications
von Herrath M and Nepom GT. Animal models of human type 1 diabetes. Nat Immunol 10:129-132, 2009.
Long SA, Walker MR, Rieck M, James E, Kwok WW, Sanda S, Pihoker C, Greenbaum C, Nepom GT, and Buckner JH. Functional islet-specific Treg can be generated from CD4+CD25- T cells of healthy and type 1 diabetic subjects. Eur J Immunol 39:612-620, 2009. PMCID: 2743096.
Gersuk, VH and Nepom GT. A real-time polymerase chain reaction assay for the rapid identification of the autoimmune disease-associated allele HLA-DQB1*0602. Tissue Antigens 73:335-340, 2009. PMCID: 3027491.
Concannon P, Rich SS, and Nepom GT. Genetics of type 1A diabetes. N Engl J Med 360:1646-1654, 2009.
Bollyky PL, Bice JB, Sweet IR, Falk BA, Gebe JA, Clark AE, Gersuk VH, Aderem A, Hawn TR, and Nepom GT. The Toll-like receptor signaling molecule Myd88 contributes to pancreatic beta-cell homeostasis in response to injury. PLoS ONE 4:e5063:1-9, 2009. PMCID: 2666970.
Bollyky PL, Falk BA, Wu RP, Buckner JH, Wight TN, and Nepom GT. Intact extracellular matrix and the maintenance of immune tolerance: high molecular weight hyaluronan promotes persistence of induced CD4+CD25+ regulatory T cells. J Leukoc Biol 86:567-572, 2009. PMCID: 2735281.
Hallmayer J, Faraco J, Lin L, Hesselson S, Winkelmann J, Kawashima M, Mayer G, Plazzi G, Nevsimalova S, Bourgin P, Hong SS-C, Honda Y, Honda M, Högl B, Longstreth WT Jr, Montplaisir J, Kemlink D, Einen M, Chen J, Musone SL, Akana M, Miyagawa T, Duan J, Desautels A, Erhardt C, Hesla PE, Poli F, Frauscher B, Jeong J-H, Lee S-P, Ton TGN, Kvale M, Kolesar L, Dobrovolná M, Nepom GT, Salomon D, Wichmann H-E, Rouleau GA, Gieger C, Levinson DF, Gejman PV, Meitinger T, Young T, Peppard P, Tokunaga K, Kwok P-Y, Risch N, and Mignot E. Narcolepsy is strongly associated with the T-cell receptor alpha locus. Nat Genet 41:708-711, 2009. PMCID: 2803042.
Yang J, Gebe JA, Huston L, James E, Tan V, Yue BB, Nepom GT, and Kwok WW. H5N1 strain-specific Hemagglutinin CD4+ T cell epitopes restricted by HLA DR4. Vaccine 27:3862-3869, 2009. PMCID: 2695938.
Standifer NE, Burwell EA, Gersuk VH, Greenbaum CJ, and Nepom GT. Changes in autoreactive T cell avidity during type 1 diabetes development. Clin Immunol 132:312-320, 2009. PMCID: 2720757.
Gebe JA, Yue BB, Unrath KA, Falk BA, and Nepom GT. Restricted autoantigen recognition associated with deletional and adaptive regulatory mechanisms. J Immunol 183:59-65, 2009. PMCID: 2811410.
Bollyky PL, Falk BA, Long SA, Preisinger A, Braun KR, Wu RP, Evanko SP, Buckner JH, Wight TN, and Nepom GT. CD44 costimulation promotes FoxP3+ regulatory T cell persistence and function via production of IL-2, IL-10, and TGF-β. J Immunol 183:2232-2241, 2009. PMCID: 3057032.
von Herrath M and Nepom GT. Remodeling rodent models to mimic human type 1 diabetes. Eur J Immunol 39:2049-2054, 2009.
Honeyman MC, Stone NL, Falk BA, Nepom G, and Harrison LC. Evidence for molecular mimicry between human T cell epitopes in rotavirus and pancreatic islet autoantigens. J Immunol 184(4):2204-2210, 2010.
Durinovic-Belló I, Wu RP, Gersuk VH, Sanda S, Shilling HG, and Nepom GT. Insulin gene VNTR genotype associates with frequency and phenotype of the autoimmune response to proinsulin. Genes Immun 11(2):188-193, 2010. PMCID: 2845516.
Vendrame F, Pileggi A, Laughlin E, Allende G, Martin-Pagola A, Molano RD, Diamantopoulos S, Standifer N, Geubtner K, Falk BA, Ichii H, Takahashi H, Snowhite I, Chen Z, Mendez A, Chen L, Sageshima J, Ruiz P, Ciancio G, Ricordi C, Reijonen H, Nepom GT, Burke GW III, and Pugliese A. Recurrence of type 1 diabetes after simultaneous pancreas-kidney transplantation, despite immunosuppression, is associated with autoantibodies and pathogenic autoreactive CD4 T-cells. Diabetes 59:947–957, 2010. PMCID: 2844842.
Song Q, Han Q, Bradshaw EM, Kent SC, Raddassi K, Nilsson B, Nepom GT, Hafler DA, and Love JC. On-chip activation and subsequent detection of individual antigen-specific T cells. Anal Chem 82:473-477, 2010. PMCID: 2828941.
Ziegler A-G and Nepom GT. Prediction and pathogenesis in type 1 diabetes. Immunity 32:468-478, 2010. PMCID: 2861716.
Bollyky PL, Evanko SP, Wu RP, Potter-Perigo S, Long SA, Kinsella B, Reijonen H, Guebtner K, Teng B, Chan CK, Braun KR, Gebe JA, Nepom GT, and Wight TN. Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse. Cell Mol Immunol 7:211-220, 2010. PMCID: 3027489.
Nepom GT. The major histocompatibility complex. In: Harrison’s Rheumatology, 2nd ed, Fauci AS, Langford CA, eds, McGraw Hill Medical, New York, Ch 2, pp 44-56, 2010.
Sanda S, Bollyky J, Standifer N, Nepom G, Hamerman JA, and Greenbaum C. Short term IL-1β blockade reduces monocyte CD11b integrin expression in an IL-8 dependent fashion in patients with type 1 diabetes. Clin Immunol 136:170-173, 2010. NIHMS: 340217.
Tan W, Wu H, Zhao J, Derber LA, Lee DM, Shadick NA, Conn DL, Smith EA, Gersuk VH, Nepom GT, Moreland LW, Furst DE, Thompson SD, Jonas BL, Holers VM, Glass DN, Chen PP, Bridges SL Jr, Weinblatt ME, Paulus HE, and Tsao BP. A functional RANKL polymorphism associated with younger age at onset of rheumatoid arthritis. Arthr Rheum 62:2864-2875, 2010. PMCID: 2944013.
Bluestone JA, Auchincloss H, Nepom GT, Rotrosen D, St. Clair EW, and Turka LA. The Immune Tolerance Network at 10 years: tolerance research at the bedside. Nat Rev Immunol 10:797-803, 2010.
Kornum BR, Kawashima M, Faraco J, Lin L, Rico TJ, Hesselson S, Axtell RC, Kuipers H, Weiner K, Hamacher A, Kassack MU, Han F, Knudsen S, Li J, Dong X, Winkelmann J, Plazzi G, Nevsimalova S, Hong S-C, Honda Y, Honda M, Högl B, Ton TGN, Montplaisir J, Bourgin P, Kemlink D, Huang Y-S, Warby S, Einen M, Eshragh JL, Miyagawa T, Desautels A, Ruppert E, Hesla PE, Poli F, Pizza F, Frauscher B, Jeong J-H, Lee S-P, Strohl KP, Longstreth WT Jr, Kvale M, Dobrovolna M, Ohayon MM, Nepom GT, Wichmann H-E, Rouleau GA, Gieger C, Levinson DF, Gejman PV, Meitinger T, Peppard P, Young T, Jennum P, Steinman L, Tokunaga K, Kwok P-Y, Risch N, Hallmayer J, and Mignot E. Common variants in P2RY11 are associated with narcolepsy. Nat Genet 43(1):66-71, 2011. PMCID: 3019286.
Pugliese A, Reijonen HK, Nepom J, and Burke GW III. Recurrence of autoimmunity in pancreas transplant patients: research update. Diabetes Manag 1(2):229-238, 2011. PMCID: 3171830.
Nepom GT, St Clair EW, and Turka LA. Challenges in the pursuit of immune tolerance. Immunol Rev 241:49-62, 2011. PMCID: 3092524.
Bollyky PL, Wu RP, Falk BA, Lord JD, Long SA, Preisinger A, Teng B, Holt GE, Standifer NE, Braun KR, Xie CF, Samuels PL, Vernon RB, Gebe JA, Wight TN, and Nepom GT. ECM components guide IL-10 producing regulatory T-cell (TR1) induction from effector memory T-cell precursors. Proc Natl Acad Sci USA 108(19):7938-7943, 2011. PMCID: 3093524.
Khadra A, Pietropaolo M, Nepom GT, and Sherman A. Investigating the role of T-cell avidity and killing efficacy in relation to type 1 diabetes prediction. PLoS ONE 6(5):e14796 (1-16), 2011. PMCID: 3091860.
Raddassi K, Kent SC, Yang J, Bourcier K, Bradshaw EM, Seyfert-Margolis V, Nepom GT, Kwok WW, and Hafler DA. Increased frequencies of myelin oligodendrocyte glycoprotein/MHC class II-binding CD4 cells in patients with multiple sclerosis. J Immunol 187:1039-1046, 2011. PMCID: 3131477.
Snir O, Rieck M, Gebe JA, Yue BB, Rawlings CA, Nepom G, Malmström V, and Buckner JH. Identification and functional characterization of T cells reactive to citrullinated-vimentin in HLA-DRB1*0401 humanized mice and RA patients. Arthritis Rheum 63(10):2873-2883, 2011. PMCID: 3174345.
Robins H, Desmarais C, Matthis J, Livingston R, Andriesen J, Reijonen H, Carlson C, Nepom G, Yee C, and Cerosaletti K. Ultra-sensitive detection of rare T cell clones. J Immunol Meth 375: 14-19, 2012. PMCID in process.
Scubert DA, Gordo S, Sabatino JJ Jr, Vardhana S, Gagnon E, Sethi DK, Seth NP, Choudhuri K, Reijonen H, Nepom GT, Evavold BD, Dustin ML, and Wucherpfennig KW. Self-reactive human CD4 T cell clones form unusual immunological synapses. J Exp Med 209:335-352, 2012. PMCID: 3280872.
Evanko SP, Potter-Perigo S, Bollyky PL, Nepom GT, and Wight TN. Hyaluronan and versican in the control of human T-lymphocyte adhesion and migration. Matrix Biol 31:90-100, 2012. PMCID: 3288568.
Nepom GT. MHC class II tetramers. J Immunol 188:2477-2482, 2012. PMCID: 3297979.
Matthis J and Nepom GT. T cell autoreactivity in the transplant milieu. Am J Transplant 12:1674-1681, 2012.
Vernon RB, Preisinger A, Gooden MD, D’Amico LA, Yue BB, Bollyky PL, Kuhr CS, Hefty TR, Nepom GT, Gebe JA. Reversal of diabetes in mice with a bioengineered islet implant incorporating a type I collagen hydrogel and sustained release of vascular endothelial growth factor. Cell Transplant 21:2099-2110, 2012. PMCID in process.
Nepom GT and Buckner JH. A functional framework for interpretation of genetic associations in T1D. Curr Opin Immunol 24:516-521, 2012.