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. Holohan DR, Van Gool F, Bluestone JA. Thymically-derived Foxp3+ regulatory T cells are the primary regulators of type 1 diabetes in the non-obese diabetic mouse model. PLoS One. 2019; 14(10):e0217728.
    View on PubMed
  2. Ferreira LMR, Muller YD, Bluestone JA, Tang Q. Next-generation regulatory T cell therapy. Nat Rev Drug Discov. 2019 Sep 20.
    View on PubMed
  3. Herold KC, Bundy BN, Long SA, Bluestone JA, DiMeglio LA, Dufort MJ, Gitelman SE, Gottlieb PA, Krischer JP, Linsley PS, Marks JB, Moore W, Moran A, Rodriguez H, Russell WE, Schatz D, Skyler JS, Tsalikian E, Wherrett DK, Ziegler AG, Greenbaum CJ. An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. N Engl J Med. 2019 08 15; 381(7):603-613.
    View on PubMed
  4. Azimi CS, Tang Q, Roybal KT, Bluestone JA. NextGen cell-based immunotherapies in cancer and other immune disorders. Curr Opin Immunol. 2019 Aug; 59:79-87.
    View on PubMed
  5. Van Gool F, Nguyen MLT, Mumbach MR, Satpathy AT, Rosenthal WL, Giacometti S, Le DT, Liu W, Brusko TM, Anderson MS, Rudensky AY, Marson A, Chang HY, Bluestone JA. A Mutation in the Transcription Factor Foxp3 Drives T Helper 2 Effector Function in Regulatory T Cells. Immunity. 2019 02 19; 50(2):362-377.e6.
    View on PubMed
  6. Dall'Era M, Pauli ML, Remedios K, Taravati K, Sandova PM, Putnam AL, Lares A, Haemel A, Tang Q, Hellerstein M, Fitch M, McNamara J, Welch B, Bluestone JA, Wofsy D, Rosenblum MD. Adoptive Treg Cell Therapy in a Patient With Systemic Lupus Erythematosus. Arthritis Rheumatol. 2019 Mar; 71(3):431-440.
    View on PubMed
  7. Bridge JA, Lee JC, Daud A, Wells JW, Bluestone JA. Cytokines, Chemokines, and Other Biomarkers of Response for Checkpoint Inhibitor Therapy in Skin Cancer. Front Med (Lausanne). 2018; 5:351.
    View on PubMed
  8. Young A, Quandt Z, Bluestone JA. The Balancing Act between Cancer Immunity and Autoimmunity in Response to Immunotherapy. Cancer Immunol Res. 2018 12; 6(12):1445-1452.
    View on PubMed
  9. Bucktrout SL, Bluestone JA, Ramsdell F. Recent advances in immunotherapies: from infection and autoimmunity, to cancer, and back again. Genome Med. 2018 10 31; 10(1):79.
    View on PubMed
  10. Esensten JH, Muller YD, Bluestone JA, Tang Q. Regulatory T-cell therapy for autoimmune and autoinflammatory diseases: The next frontier. J Allergy Clin Immunol. 2018 12; 142(6):1710-1718.
    View on PubMed
  11. Bluestone JA, Tang Q. Treg cells-the next frontier of cell therapy. Science. 2018 10 12; 362(6411):154-155.
    View on PubMed
  12. Bluestone JA. Chance favours the prepared mind. Nat Rev Immunol. 2018 09; 18(9):541.
    View on PubMed
  13. Spangler JB, Trotta E, Tomala J, Peck A, Young TA, Savvides CS, Silveria S, Votavova P, Salafsky J, Pande VS, Kovar M, Bluestone JA, Garcia KC. Engineering a Single-Agent Cytokine/Antibody Fusion That Selectively Expands Regulatory T Cells for Autoimmune Disease Therapy. J Immunol. 2018 10 01; 201(7):2094-2106.
    View on PubMed
  14. Abbas AK, Trotta E, R Simeonov D, Marson A, Bluestone JA. Revisiting IL-2: Biology and therapeutic prospects. Sci Immunol. 2018 07 06; 3(25).
    View on PubMed
  15. 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. Author Correction: Discovery of stimulation-responsive immune enhancers with CRISPR activation. Nature. 2018 07; 559(7715):E13.
    View on PubMed
  16. Trotta E, Bessette PH, Silveria SL, Ely LK, Jude KM, Le DT, Holst CR, Coyle A, Potempa M, Lanier LL, Garcia KC, Crellin NK, Rondon IJ, Bluestone JA. A human anti-IL-2 antibody that potentiates regulatory T cells by a structure-based mechanism. Nat Med. 2018 07; 24(7):1005-1014.
    View on PubMed
  17. Stamatouli AM, Quandt Z, Perdigoto AL, Clark PL, Kluger H, Weiss SA, Gettinger S, Sznol M, Young A, Rushakoff R, Lee J, Bluestone JA, Anderson M, Herold KC. Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors. Diabetes. 2018 08; 67(8):1471-1480.
    View on PubMed
  18. Wang D, Quiros J, Mahuron K, Pai CC, Ranzani V, Young A, Silveria S, Harwin T, Abnousian A, Pagani M, Rosenblum MD, Van Gool F, Fong L, Bluestone JA, DuPage M. Targeting EZH2 Reprograms Intratumoral Regulatory T Cells to Enhance Cancer Immunity. Cell Rep. 2018 06 12; 23(11):3262-3274.
    View on PubMed
  19. Sneddon JB, Tang Q, Stock P, Bluestone JA, Roy S, Desai T, Hebrok M. Stem Cell Therapies for Treating Diabetes: Progress and Remaining Challenges. Cell Stem Cell. 2018 Jun 01; 22(6):810-823.
    View on PubMed
  20. Hua J, Inomata T, Chen Y, Foulsham W, Stevenson W, Shiang T, Bluestone JA, Dana R. Pathological conversion of regulatory T cells is associated with loss of allotolerance. Sci Rep. 2018 05 04; 8(1):7059.
    View on PubMed

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