Gerald T. Nepom, MD, PhD
Background Information
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 a Member of the Benaroya Research Institute at Virginia Mason (BRI) and served as Director of BRI from 1985 through 2015. In 2010, Dr. Nepom also became Director of the Immune Tolerance Network (ITN), sponsored by the National Institute of Allergy and Infectious Diseases (NIAID).
Area 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.
Immune Tolerance Network (ITN)
Featured Publications
Ramsey BW, Nepom GT, Lonial S. Academic, Foundation, and Industry Collaboration in Finding New Therapies. N Engl J Med. 2017 May 4;376(18):1762-1769. PMID: 28467868.
Yang J, Wen X, Xu H, Torres-Chinn N, Speake C, Greenbaum CJ, Nepom GT, Kwok WW. Antigen-Specific T Cell Analysis Reveals That Active Immune Responses to β Cell Antigens Are Focused on a Unique Set of Epitopes. J Immunol. 2017 May 26. pii: 1601570. doi: 10.4049/jimmunol.1601570. PubMed PMID: 28550202.
Cerosaletti K, Barahmand-Pour-Whitman F, Yang J, DeBerg HA, Dufort MJ, Murray SA, Israelsson E, Speake C, Gersuk VH, Eddy JA, Reijonen H, Greenbaum CJ, Kwok WW, Wambre E, Prlic M, Gottardo R, Nepom GT, Linsley PS. Single-Cell RNA Sequencing Reveals Expanded Clones of Islet Antigen-Reactive CD4(+) T Cells in Peripheral Blood of Subjects with Type 1 Diabetes. J Immunol. 2017 May 31. doi: 10.4049/jimmunol.1700172. PubMed PMID: 28566371.
Long SA, Thorpe J, Herold KC, Ehlers M, Sanda S, Lim N, Linsley PS, Nepom GT, Harris KM. Remodeling T cell compartments during anti-CD3 immunotherapy of type 1 diabetes. Cellular immunology. 2017 September;319:3-9. PubMed PMID: 28844471; PubMed Central PMCID: PMC5614459.
Renand A, Shamji MH, Harris KM, Qin T, Wambre E, Scadding GW, Wurtzen PA, Till SJ, Togias A, Nepom GT, Kwok WW, Durham SR. Synchronous Immune Alterations Mirror Clinical Response During Allergen Immunotherapy. J Allergy Clin Immunol. 2017 Nov 8. pii: S0091-6749(17)31735-9. doi: 10.1016/j.jaci.2017.09.041. PubMed PMID: 29128670.
Asare AL, Carey VJ, Rotrosen D, Nepom GT. Clinical trial data access: Opening doors with TrialShare. J Allergy Clin Immunol. 2016 Sep;138(3):724-6. doi: 10.1016/j.jaci.2016.05.034. PubMed PMID: 27474121.
Long SA, Thorpe J, DeBerg HA, Gersuk V, Eddy J, Harris KM, Ehlers M, Herold K, Nepom GT, Linsley PS. Partially exhausted CD8 T cells are associated with clinical response to teplizumab in new-onset type 1 diabetes. Science Immunology 18 Nov 2016:Vol. 1, Issue 5, doi: 10.1126/sciimmunol.aai7793.
Bonifacio E, Mathieu C, Nepom GT, Ziegler AG, Anhalt H, Haller MJ, Harrson LC, Hebrok M, Kushner JA, Norris JM, Peakman M, Powers AC, Todd JA, Atkinson MA. Rebranding asymptomatic type 1 diabetes: the case for autoimmune beta cell disorder as a pathological and diagnostic entity. Diabetologia. 2017 Jan;60(1):35-38. doi: 10.1007/s00125-016-4144-8. PubMed PMID: 27785529.
Rigby MR, Harris KM, Pinckney A, DiMeglio LA, Rendell MS, Felner EI, Dostou JM, Gitelman SE, Griffin KJ, Tsalikian E, Gottlieb PA, Greenbaum CJ, Sherry NA, Moore WV, Monzavi R, Willi SM, Raskin P, Keyes-Elstein L, Long SA, Kanaparthi S, Lim N, Phippard D, Soppe CL, Fitzgibbon ML, McNamara J, Nepom GT, Ehlers MR. Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients. J Clin Invest. 2015 Aug 3;125(8):3285-96. doi: 10.1172/JCI81722. PubMed PMID: 26193635; PubMed Central PMCID: PMC4623571.
Odegard JM, Nepom GT, Wambre E. Biomarkers for antigen immunotherapy in allergy and type 1 diabetes. Clin Immunol. 2015 Nov;161(1):44-50. doi: 10.1016/j.clim.2015.05.023. PubMed PMID: 26122171; PubMed Central PMCID: PMC4628579.
Cao Y, Goods BA, Raddassi K, Nepom GT, Kwok WW, Love JC, Hafler DA. Functional inflammatory profiles distinguish myelin-reactive T cells from patients with multiple sclerosis. Sci Transl Med. 2015 May 13;7(287):287ra74. doi: 10.1126/scitranslmed.aaa8038. PubMed PMID: 25972006; PubMed Central PMCID: PMC4497538.
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 3721519.
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. PMID: 22642536.
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: 3829609.
Nepom GT and Buckner JH. A functional framework for interpretation of genetic associations in T1D. Curr Opin Immunol 24:516-521, 2012. PMID: 22841349. PMCID: 4260931.
Nepom GT, Ehlers M, and Mandrup-Poulsen T. Anti-cytokine therapies in T1D: Concepts and strategies. Clin Immunol 149(3):279-285, 2013. PMID: 23510726. PMCID: 3700624.
Ahmed ST, Akirav E, Bradshaw E, Buckner J, McKinney E, Quintana FJ, Waldron-Lynch F, and Nepom J. Immunological biomarkers: Catalysts for translational advances in autoimmune diabetes. Clin Exp Immunol 172:178-185, 2013. PMID: 23574315. PMCID: 3628321.
Ehlers MR, Nepom GT. Immune-directed therapy for type 1 diabetes in the clinic--The Immune Tolerance Network (ITN) experience. Rev Diabet Stud 9(4):359-371, 2012. PMID: 23804273. PMCID: 3740703.
Obermoser G, Presnell S, Domico K, Xu H, Wang Y, Anguiano E, Thompson-Snipes L, Ranganathan R, Zeitner B, Bjork A, Anderson D, Speake C, Ruchaud E, Skinner J, Alsina L, Sharma M, Dutartre H, Cepika A, Israelsson E, Nguyen P, Nguyen QA, Harrod AC, Zurawski SM, Pascual V, Ueno H, Nepom GT, Quinn C, Blankenship D, Palucka K, Banchereau J, and Chaussabel D. Systems scale interactive exploration reveals quantitative and qualitative differences in response to influenza and pneumococcal vaccines. Immunity 38(4):831-844, 2013. PMID: 23601689. PMCID: 3681204.
Bollyky PL, Vernon RB, Falk BA, Preisinger A, Gooden MD, Nepom GT, and Gebe JA. IL-10 induction from implants delivering pancreatic islets and hyaluronan. J Diabet Res 2013:342479, 2013. PMID: 23971054. PMCID: 3736405.
Dahan R, Gebe JA, Preisinger A, James EA, Tendler M, Nepom GT, and Reiter Y. Antigen-specific immunomodulation for type 1 diabetes by novel recombinant antibodies directed against diabetes associates auto-reactive T cell epitope. J Autoimmun 47:83-93, 2013. PMID: 24090977. No federal support.
Rigby MR, DiMeglio LA, Rendell MS, Felner EI, Dostou JM, Gitelman SE, Patel CM, Griffin KJ, Tsalikian E, Gottlieb PA, Greenbaum CJ, Sherry NA, Moore WV, Monzavi R, Willi SM, Raskin P, Moran A, Russell WE, Pinckney A, Keyes-Elstein L, Howell M, Aggarwal S, Lim N, Phippard D, Nepom GT, McNamara J, Ehlers MR, and the T1DAL Study Team. Targeting of memory T cells with alefacept in new-onset type 1 diabetes (T1DAL study): 12 month results of a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Diab Endocrinol 1(4):284-294, 2013. PMID: 24622414. PMCID: 3957186.
Smilek DE, Ehlers MR, and Nepom GT. Restoring the balance: immunotherapeutic combinations for autoimmune disease. Dis Model Mech 7(5):503-513, 2014. PMID: 24795433. PMCID: 4007402.
Mason MJ, Speake C, Gersuk VH, Nguyen Q-A, O’Brien KK, Odegard JM, Buckner JH, Greenbaum CJ, Chaussabel D, and Nepom GT. Low HERV-K(C4) copy number is associated with type 1 diabetes. Diabetes 63(5):1789-1795, 2014. PMID: 24430436. PMCID in process.
Durinovic-Belló I, Gersuk VH, Ni C, Wu R, Thorpe J, Jospe N, Sanda S, Greenbaum CJ, and Nepom GT. Avidity-dependent programming of autoreactive T cells in T1D. PLoS ONE 9(5):e98074, 2014. PMID: 24844227. PMCID: 4028311.
