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. He attended 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 April 2010, Dr. Nepom was named Director of the Immune Tolerance Network (ITN) by the National Institute of Allergy and Infectious Diseases (NIAID). ITN is one of the largest government-funded clinical research networks in the country working to establish new treatments for diseases of the immune system. Dr. Nepom is also immediate past president of FOCIS, the Federation of Clinical Immunology Societies, a world-wide professional organization dedicated to interdisciplinary research and education in translational immunology.
Areas of Research
Projects in Dr. Nepom's laboratory are focused on identifying and understanding molecular and genetic mechanisms contributing to triggering of autoimmune disorders. A combination of in vitro studies, preclinical models, and human T cell profiling is used to evaluate autoreactive T cell lineage and fate determination. Translational and clinical applications include evaluation of the role of HLA class II genes in the etiology of type I diabetes and adult and juvenile rheumatoid arthritis, and use of immunological monitoring tools for predicting disease susceptibility and response to therapy in clinical trials.
Selected Publications
Ettinger R, Papadopoulos G, Moustakas A, Nepom GT, and Kwok WW. Allelic variation in key peptide-binding pockets discriminates between closely related diabetes-protective and diabetes-susceptible HLA-DQB106 alleles. J Immunol 176:1988 1998, 2006.
Steere A, Klitz W, Drouin E, Falk B, Kwok W, Nepom GT, and Baxter-Lowe LA. Correlation of antibiotic-refractory lyme arthritis with HLA-DR molecules that bind the outer surface protein-A T cell epitope of Borrelia burgdorferi. J Exp Med 203:961 971, 2006.
Walker M and Nepom GT. Major histocompatibility complex and autoimmunity. In: The Autoimmune Diseases, Rose N and McKay I, eds, Elsevier Science, pp 45 56, 2005.
Khanna D, Wu H, Park G, Gersuk V, Gold RH, Nepom GT, Wong WK, Sharp JT, Reed EF, Paulus HE, and Tsao BP; Western Consortium of Practicing Rheumatologists. Association of tumor necrosis factor alpha polymorphism, but not the shared epitope, with increased radiographic progression in a seropositive rheumatoid arthritis inception cohort. Arthritis Rheum 54:1105 1116, 2006.
Durinovic-Bello I, Rosinger S, Olson J, Congia M, Ahmad RC, Rickert M, Wong H, Hampl J, Kalbacher H, Drijfhout JW, Mellins ED, Al-Dahouk S, Roep BO, Nepom GT, Kamradt T, Karges W, Boehm BO, McDevitt HO, Sønderstrup G. DRB1*0401-restricted human T cell clone specific for the major proinsulin 73-90 epitope expresses a down-regulatory T helper 2 phenotype. Proc Natl Acad Sci USA 103:11683 11688, 2006.
Gersuk V and Nepom GT. A real-time PCR approach for rapid high resolution subtyping of HLA-DRB1*04. J Immunol Meth 317:64 70, 2006.
Gebe J, Rock K, Falk B, Ito K, Wen L, and Nepom GT. Age-dependent loss of tolerance to an immunodominant epitope of glutamic acid decarboxylase precedes diabetes in diabetic prone RIP-B7/DR4 mice. J Clin Immunol 121:294 304, 2006.
Standifer N, Ouyang Q, Panagiotopoulos C, Verchere CB, Tan R, Greenbaum CJ, Pihoker C, and Nepom GT. Identification of novel HLA-A*0201 restricted epitopes in recent-onset type 1 diabetic subjects and antibody-positive relatives. Diabetes 55:3061 3067, 2006.
Beeton C, Wulff H, Standifer NE, Azam P, Mullen KM, Pennington MW, Kolski-Andreaco A, Wei E, Grino A, Counts DR, Wang PH, LeeHealey CJ, Andrews BS, Sankaranarayanan A, Homerick D, Roeck WW, Tehranzadeh J, Stanhope KL, Zimin P, Havel PJ, Griffey S, Knaus H-G, Nepom GT, Gutman GA, Calabresi PA, and Chandy KG. Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases. Proc Natl Acad Sci USA 103:17414 17419, 2006.
Seyfert-Margolis V, Gisler TD, Asare AL, Wang RS, Dosch HM, Brooks-Worrell B, Eisenbarth GS, Palmer JP, Greenbaum CJ, Gitelman SE, Nepom GT, Bluestone JA, and Herold KC. Analysis of T-cell assays to measure autoimmune responses in subjects with type 1 diabetes: results of a blinded controlled study. Diabetes 55:2588 2594, 2006.
Ouyang Q, Standifer N, Qin H, Gottlieb P, Verchere CB, Nepom GT, Tan R, and Panagiotopoulos C. Recognition of HLA class I-restricted beta cell epitopes in type 1 diabetes. Diabetes 55:3068 3074, 2006.
Laughlin EM, Miller JD, James E, Fillos D, Ibegbu CC, Mittler R, Akondy R, Kwok W, Ahmed R, and Nepom G. Antigen-specific CD4+ T cells recognize epitopes of protective antigen following AVA vaccination. Infect Immunol 75:1852 1860, 2007.
Gebe J, Falk B, Unrath K, and Nepom GT. Autoreactive T cells in a partially humanized murine model of T1D. Ann NY Acad Sci 1103:69 76, 2007.
Bollyky PL, Lord JD, Masewicz SA, Evanko SP, Buckner JH, Wight T, and Nepom GT. Cutting edge: High molecular weight hyaluronan promotes the suppressive effects of CD4+CD25+ regulatory T cells. J Immunol 179: 744–747, 2007.
Kannian P, Drouin E, Glickstein L, Kwok W, Nepom GT, and Steere AC. Decline in the frequencies of Borrelia burgdorferi OspA161-175 specific T cells after antibiotic therapy in HLA-DRB1*0401 positive patients with antibiotic resistant or antibiotic refractory Lyme arthritis. J Immunol 179:6336-6342, 2007.
Gebe JA, Unrath KA, Yue BB, Miyake T, Falk BA, Nepom GT. Autoreactive human T-cell receptor initiates insulitis and impaired glucose tolerance in HLA DR4 transgenic mice. J Autoimmun Oct 17 2007, [Epub ahead of print], doi:10.1016/j.jaut.2007.08.001
Couch ME, Ferris RL, Brennan JA, Koch WM, Jaffee EM, Leibowitz MS, Nepom GT, Erlich HA, Sidransky D. Alteration of cellular and humoral immunity by mutant p53 protein and processed mutant peptide in head and neck cancer. Clin Cancer Res. 13(23):7199-206, 2007.
Drouin EE, Glickstein L, Kwok WW, Nepom GT, and Steere AC. Human homologues of a Borrelia T cell epitope associated with antibiotic-refractory Lyme arthritis. Mol Immunol 45:180-189, 2008.