University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Jeffrey Bluestone, PhD

Jeffrey Bluestone, PhD

Professor, School of Medicine, UCSF
Director, Hormone Research Institute, Diabetes Center
A.W. and Mary Margaret Clausen Distinguished Professorship in Metabolism and Endocrinology, UCSF

Cancer Center Program Memberships

Cancer Immunology

Research Summary

Jeffrey Bluestone, PhD, is the A.W. and Mary Margaret Clausen Distinguished Professor of Metabolism and Endocrinology and is the Director of the Hormone Research Institute in the Diabetes Center. His research over the past 25 years has focused on understanding the basic processes that control T cell activation and immune tolerance in autoimmunity and organ transplantation. He and members of his lab have developed soluble receptor antagonists; monoclonal antibodies and animals deficient in individual members of TCR and co-stimulatory pathways to define their individual roles in transplant rejection and autoimmunity including a special emphasis on a specialized subset of T cells termed “regulatory T cells” (Treg). Tregs control fundamental aspect of immune homeostasis. During the last several years, his research has adapted the animal studies using biologics and cell based therapies to develop therapeutics that can be used in humans with autoimmunity and under conditions of allotransplant rejection. Moreover, a strong role for antigen-specific Tregs have been found in these model systems and further evidence in humanized mice and transplant patients that alloantigen-specific Tregs are more effective. Thus, the major goal of this work is to identify the antigen-specificity of thymic- and peripherally-derived Tregs with the expectation that these TCRs can be adapted for immunotherapy. Finally, his lab initiated several projects to determine mechanisms that control Treg stability. The goal is to develop approaches using pharmacogenomics to either stabilize or destabilize Tregs in autoimmunity and cancer.

In March 2010 Dr. Bluestone was appointed executive vice chancellor and provost at the University of California San Francisco (UCSF) serving as chief academic officer guiding the research and academic enterprise advancing the campus priorities in close collaboration with the chancellor and the campus leadership teams, and to oversee the campus ethics and compliance enterprise. Previously he served in a number of posts including Director of theUCSF Diabetes Center, as Director of the Immune Tolerance Network.

In June 2008 Dr. Bluestone served as interim vice chancellor of research, directing the advancement of cross-campus research initiatives, such as enhancing core research facilities. In this capacity, he played a leading role in coordinating and integrating current research cores. He worked also to strengthen external research partnerships, particularly with industry, and focused on facilitating the translation of UCSF discoveries into public benefit.

In 2009, Dr. Bluestone led the UCSF committee to strategize and secure funds available through the American Recovery and Reinvestment Act, making the campus one of the top institutional recipients in the nation of science-based stimulus funds.

Dr. Bluestone joined the UCSF faculty in 2000. He is an international leader in the field of immunotherapy, with a stellar record of scholarly achievement and a decade of significant contributions to the research enterprise at UCSF, including the creation and directorship of an integrated UCSF Diabetes Center to focus on translating basic research in both type 1 and type 2 diabetes into improved therapies for patients. He also founded and directed the Immune Tolerance Network, a consortium of more than 1,000 of the world’s leading scientific researchers and clinical specialists from nearly 50 institutions, with the mission of testing new therapies to promote immune tolerance in transplantation, autoimmune diseases, asthma and allergic diseases.

As a research scientist, Dr. Bluestone has helped clarify the body’s immune response on a molecular level. His systematic investigation has catalyzed recent progress in stem cell research, islet cell transplantation and immune tolerance therapies – experimentation that has formidably translated into drugs to treat human disease.

Through his 30-year scientific career, he has authored more than 300 peer-reviewed publications that include prominent papers in Nature, Nature Immunology, and the Journal of Immunology and Diabetes. He has received numerous accolades for his work, including his 2006 election to the American Academy of Arts and Sciences, the Mary Tyler Moore & Robert Levine Excellence in Clinical Research Award from the Juvenile Diabetes Research Foundation, and the distinguished alumni award from the Cornell Graduate School of Medical Science.

Prior to joining UCSF, Bluestone was at the University of Chicago, where he was a member of the Ben May Institute for Cancer Research, rising over 13 years from an associate professor to the director of the institute. He had previously worked for seven years in various roles at the National Cancer Institute of the National Institutes of Health, ultimately becoming a senior investigator in the Immunology Branch of the National Cancer Institute.

Dr. Bluestone earned both his BS in biology and his MS in microbiology from Rutgers State University, and his PhD in immunology from the Cornell Graduate School of Medical Science (Sloan-Kettering Division).

Education

Cook College, Rutgers University, B.S., 1974, Biology
Rutgers - State University, NJ, M.S., 1977, Microbiology
Cornell Graduate School of Medical Science (Sloan-Kettering Division), Ph.D., 1980, Immunology


Professional Experience

  • 1980-1982
    Anna Fuller Fund Postdoctoral Fellow, Immunology Branch, National Cancer Institute, NIH
  • 1982-1982
    Laboratory Leader, Senior Staff Fellow, Transplantation Biology Section, Immunology Branch, NCI, NIH
  • 1986-1982
    Senior Investigator, Transplantation Biology Section, Immunology Branch, NCI, NIH
  • 1987-1992
    Associate Professor, Ben May Institute, Dept. of Pathology and the Committee on Immunology, University of Chicago
  • 1991-2002
    Professor, Ben May Institute, Department of Pathology and the Committee on Immunology, University of Chicago and Chairman, Committee on Immunology
  • 1995-2002
    Director, Ben May Institute for Cancer Research
  • 1999-present
    Director, Juvenile Diabetes Center, University of Chicago and University of Minnesota
  • 1999-present
    Director, Immune Tolerance Network
  • 2000-present
    A.W. and Mary Margaret Clausen Distinguished Professor of Metabolism and Endocrinology; and Director, UCSF Diabetes Center, the Metabolic Research Unit and the Hormone Research Institute, UCSF

Honors & Awards

  • 1987 -1989
    Faculty Scholar, Gould Foundation
  • 1989
    Faculty Scholar, American Cancer Society
  • 1997
    Senior Fellowship, Guggenheim Foundation
  • 1997
    Senior Research Fellowship, Fogarty Foundation
  • 1998
    Distinguished Alumni Award, Cornell Medical School
  • 2004
    Gerold & Kayla Grodsky Basic Science Award, Juvenile Diabetes Research Foundation
  • 2004
    Roche Distinguished Research Award, American Society for Transplantation
  • 2005
    Mary Tyler Moore & Robert Levine Excellence in Clinical Research Award, Juvenile Diabetes Research Foundation
  • 2006
    Elected Member, American Academy of Arts and Sciences
  • 2008
    Scholar Award, Juvenile Diabetes Research Foundation
  • 2010
    Elliott Middleton Memorial Lectureship, American Academy of Allergy, Asthma, & Immunology
  • 2013
    Elected Member, National Academy of Medicine
  • 2015
    Outstanding Mentorship Award, American Society of Transplantation
  • 2015
    President-Elect, Federation of Clinical Immunology Societies
  • 2016
    Blue Ribbon Panel on Cancer Research (Biden Moonshot Program), National Cancer Foundation

Selected Publications

  1. Sockolosky JT, Trotta E, Parisi G, Picton L, Su LL, Le AC, Chhabra A, Silveria SL, George BM, King IC, Tiffany MR, Jude K, Sibener LV, Baker D, Shizuru JA, Ribas A, Bluestone JA, Garcia KC. Selective targeting of engineered T cells using orthogonal IL-2 cytokine-receptor complexes. Science. 2018 03 02; 359(6379):1037-1042.
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  2. Jaffee EM, Dang CV, Agus DB, Alexander BM, Anderson KC, Ashworth A, Barker AD, Bastani R, Bhatia S, Bluestone JA, Brawley O, Butte AJ, Coit DG, Davidson NE, Davis M, DePinho RA, Diasio RB, Draetta G, Frazier AL, Futreal A, Gambhir SS, Ganz PA, Garraway L, Gerson S, Gupta S, Heath J, Hoffman RI, Hudis C, Hughes-Halbert C, Ibrahim R, Jadvar H, Kavanagh B, Kittles R, Le QT, Lippman SM, Mankoff D, Mardis ER, Mayer DK, McMasters K, Meropol NJ, Mitchell B, Naredi P, Ornish D, Pawlik TM, Peppercorn J, Pomper MG, Raghavan D, Ritchie C, Schwarz SW, Sullivan R, Wahl R, Wolchok JD, Wong SL, Yung A. Future cancer research priorities in the USA: a Lancet Oncology Commission. Lancet Oncol. 2017 Nov; 18(11):e653-e706.
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  3. Yeh WI, Seay HR, Newby B, Posgai AL, Moniz FB, Michels A, Mathews CE, Bluestone JA, Brusko TM. Avidity and Bystander Suppressive Capacity of Human Regulatory T Cells Expressing De Novo Autoreactive T-Cell Receptors in Type 1 Diabetes. Front Immunol. 2017; 8:1313.
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  4. Simeonov DR, Gowen BG, Boontanrart M, Roth TL, Gagnon JD, Mumbach MR, Satpathy AT, Lee Y, Bray NL, Chan AY, Lituiev DS, Nguyen ML, Gate RE, Subramaniam M, Li Z, Woo JM, Mitros T, Ray GJ, Curie GL, Naddaf N, Chu JS, Ma H, Boyer E, Van Gool F, Huang H, Liu R, Tobin VR, Schumann K, Daly MJ, Farh KK, Ansel KM, Ye CJ, Greenleaf WJ, Anderson MS, Bluestone JA, Chang HY, Corn JE, Marson A. Discovery of stimulation-responsive immune enhancers with CRISPR activation. Nature. 2017 09 07; 549(7670):111-115.
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  5. Chandran S, Tang Q, Sarwal M, Laszik ZG, Putnam AL, Lee K, Leung J, Nguyen V, Sigdel T, Tavares EC, Yang JYC, Hellerstein M, Fitch M, Bluestone JA, Vincenti F. Polyclonal Regulatory T Cell Therapy for Control of Inflammation in Kidney Transplants. Am J Transplant. 2017 Nov; 17(11):2945-2954.
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  6. June CH, Warshauer JT, Bluestone JA. Corrigendum: Is autoimmunity the Achilles' heel of cancer immunotherapy? Nat Med. 2017 Aug 04; 23(8):1004.
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  7. June CH, Warshauer JT, Bluestone JA. Is autoimmunity the Achilles' heel of cancer immunotherapy? Nat Med. 2017 05 05; 23(5):540-547.
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  8. Morita S, Villalta SA, Feldman HC, Register AC, Rosenthal W, Hoffmann-Petersen IT, Mehdizadeh M, Ghosh R, Wang L, Colon-Negron K, Meza-Acevedo R, Backes BJ, Maly DJ, Bluestone JA, Papa FR. Targeting ABL-IRE1a Signaling Spares ER-Stressed Pancreatic ß Cells to Reverse Autoimmune Diabetes. Cell Metab. 2017 05 02; 25(5):1207.
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  9. Morita S, Villalta SA, Feldman HC, Register AC, Rosenthal W, Hoffmann-Petersen IT, Mehdizadeh M, Ghosh R, Wang L, Colon-Negron K, Meza-Acevedo R, Backes BJ, Maly DJ, Bluestone JA, Papa FR. Targeting ABL-IRE1a Signaling Spares ER-Stressed Pancreatic ß Cells to Reverse Autoimmune Diabetes. Cell Metab. 2017 Apr 04; 25(4):883-897.e8.
    View on PubMed
  10. Bluestone JA. FOXP3, the Transcription Factor at the Heart of the Rebirth of Immune Tolerance. J Immunol. 2017 02 01; 198(3):979-980.
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  11. Seay HR, Putnam AL, Cserny J, Posgai AL, Rosenau EH, Wingard JR, Girard KF, Kraus M, Lares AP, Brown HL, Brown KS, Balavage KT, Peters LD, Bushdorf AN, Atkinson MA, Bluestone JA, Haller MJ, Brusko TM. Expansion of Human Tregs from Cryopreserved Umbilical Cord Blood for GMP-Compliant Autologous Adoptive Cell Transfer Therapy. Mol Ther Methods Clin Dev. 2017 Mar 17; 4:178-191.
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  12. Esensten JH, Bluestone JA, Lim WA. Engineering Therapeutic T Cells: From Synthetic Biology to Clinical Trials. Annu Rev Pathol. 2017 Jan 24; 12:305-330.
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  13. Esensten JH, Helou YA, Chopra G, Weiss A, Bluestone JA. CD28 Costimulation: From Mechanism to Therapy. Immunity. 2016 05 17; 44(5):973-88.
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  14. Roan F, Stoklasek TA, Whalen E, Molitor JA, Bluestone JA, Buckner JH, Ziegler SF. Correction: CD4+ Group 1 Innate Lymphoid Cells (ILC) Form a Functionally Distinct ILC Subset That Is Increased in Systemic Sclerosis. J Immunol. 2016 May 01; 196(9):3966.
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  15. Gitelman SE, Bluestone JA. Regulatory T cell therapy for type 1 diabetes: May the force be with you. J Autoimmun. 2016 07; 71:78-87.
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  16. Gitelman SE, Gottlieb PA, Felner EI, Willi SM, Fisher LK, Moran A, Gottschalk M, Moore WV, Pinckney A, Keyes-Elstein L, Harris KM, Kanaparthi S, Phippard D, Ding L, Bluestone JA, Ehlers MR. Antithymocyte globulin therapy for patients with recent-onset type 1 diabetes: 2 year results of a randomised trial. Diabetologia. 2016 06; 59(6):1153-61.
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  17. DuPage M, Bluestone JA. Harnessing the plasticity of CD4(+) T cells to treat immune-mediated disease. Nat Rev Immunol. 2016 Mar; 16(3):149-63.
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  18. Roan F, Stoklasek TA, Whalen E, Molitor JA, Bluestone JA, Buckner JH, Ziegler SF. CD4+ Group 1 Innate Lymphoid Cells (ILC) Form a Functionally Distinct ILC Subset That Is Increased in Systemic Sclerosis. J Immunol. 2016 Mar 01; 196(5):2051-2062.
    View on PubMed
  19. Perdigoto AL, Chatenoud L, Bluestone JA, Herold KC. Inducing and Administering Tregs to Treat Human Disease. Front Immunol. 2015; 6:654.
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  20. Bluestone JA, Buckner JH, Fitch M, Gitelman SE, Gupta S, Hellerstein MK, Herold KC, Lares A, Lee MR, Li K, Liu W, Long SA, Masiello LM, Nguyen V, Putnam AL, Rieck M, Sayre PH, Tang Q. Type 1 diabetes immunotherapy using polyclonal regulatory T cells. Sci Transl Med. 2015 Nov 25; 7(315):315ra189.
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