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)."

Research Funding

  • July 1, 1979 - June 30, 2024 - Interdisciplinary Training Program in Immunology, Co-Principal Investigator. Sponsor: NIH/NIAID, Sponsor Award ID: T32AI007090
  • September 20, 2017 - August 31, 2021 - Designer Tregs for restoring tolerance in patients with type 1 diabetes, Principal Investigator. Sponsor: NIH/NIDDK, Sponsor Award ID: UC4DK116264
  • June 8, 2016 - May 31, 2021 - Disruption of T cell tolerance in type 1 diabetes, Co-Investigator. Sponsor: NIH/NIAID, Sponsor Award ID: P01AI118688
  • July 1, 2016 - June 30, 2020 - Using human stem cell-derived thymic epithelium to remodel T1D immune tolerance, Co-Principal Investigator. Sponsor: NIH/NIDDK, Sponsor Award ID: U01DK107383

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

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. Bayless NL, Bluestone JA, Bucktrout S, Butterfield LH, Jaffee EM, Koch CA, Roep BO, Sharpe AH, Murphy WJ, Villani AC, Walunas TL. Development of preclinical and clinical models for immune-related adverse events following checkpoint immunotherapy: a perspective from SITC and AACR. J Immunother Cancer. 2021 Sep; 9(9).  View on PubMed
  2. Bluestone JA, Buckner JH, Herold KC. Immunotherapy: Building a bridge to a cure for type 1 diabetes. Science. 2021 Jul 30; 373(6554):510-516.  View on PubMed
  3. Dong S, Hiam-Galvez KJ, Mowery CT, Herold KC, Gitelman SE, Esensten JH, Liu W, Lares AP, Leinbach AS, Lee M, Nguyen V, Tamaki SJ, Tamaki W, Tamaki CM, Mehdizadeh M, Putnam AL, Spitzer MH, Ye CJ, Tang Q, Bluestone JA. The effects of low-dose IL-2 on Treg adoptive cell therapy in patients with Type 1 diabetes. JCI Insight. 2021 Jul 29.  View on PubMed
  4. Gitelman SE, Bundy BN, Ferrannini E, Lim N, Blanchfield JL, DiMeglio LA, Felner EI, Gaglia JL, Gottlieb PA, Long SA, Mari A, Mirmira RG, Raskin P, Sanda S, Tsalikian E, Wentworth JM, Willi SM, Krischer JP, Bluestone JA, Gleevec Trial Study Group . Imatinib therapy for patients with recent-onset type 1 diabetes: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Diabetes Endocrinol. 2021 08; 9(8):502-514.  View on PubMed
  5. Muller YD, Nguyen DP, Ferreira LMR, Ho P, Raffin C, Valencia RVB, Congrave-Wilson Z, Roth TL, Eyquem J, Van Gool F, Marson A, Perez L, Wells JA, Bluestone JA, Tang Q. The CD28-Transmembrane Domain Mediates Chimeric Antigen Receptor Heterodimerization With CD28. Front Immunol. 2021; 12:639818.  View on PubMed
  6. Kang JH, Bluestone JA, Young A. Predicting and Preventing Immune Checkpoint Inhibitor Toxicity: Targeting Cytokines. Trends Immunol. 2021 04; 42(4):293-311.  View on PubMed
  7. Young A, Bluestone JA. At the Heart of Immune Checkpoint Inhibitor-Induced Immune Toxicity. Cancer Discov. 2021 Mar; 11(3):537-539.  View on PubMed
  8. Su Y, Chen D, Yuan D, Lausted C, Choi J, Dai CL, Voillet V, Duvvuri VR, Scherler K, Troisch P, Baloni P, Qin G, Smith B, Kornilov SA, Rostomily C, Xu A, Li J, Dong S, Rothchild A, Zhou J, Murray K, Edmark R, Hong S, Heath JE, Earls J, Zhang R, Xie J, Li S, Roper R, Jones L, Zhou Y, Rowen L, Liu R, Mackay S, O'Mahony DS, Dale CR, Wallick JA, Algren HA, Zager MA, ISB-Swedish COVID19 Biobanking Unit , Wei W, Price ND, Huang S, Subramanian N, Wang K, Magis AT, Hadlock JJ, Hood L, Aderem A, Bluestone JA, Lanier LL, Greenberg PD, Gottardo R, Davis MM, Goldman JD, Heath JR. Multi-Omics Resolves a Sharp Disease-State Shift between Mild and Moderate COVID-19. Cell. 2020 12 10; 183(6):1479-1495.e20.  View on PubMed
  9. Lee JC, Mehdizadeh S, Smith J, Young A, Mufazalov IA, Mowery CT, Daud A, Bluestone JA. Regulatory T cell control of systemic immunity and immunotherapy response in liver metastasis. Sci Immunol. 2020 10 02; 5(52).  View on PubMed
  10. Bluestone JA, Tang Q. Solving the Puzzle of Immune Tolerance for ß-Cell Replacement Therapy for Type 1 Diabetes. Cell Stem Cell. 2020 10 01; 27(4):505-507.  View on PubMed
  11. Schumann K, Raju SS, Lauber M, Kolb S, Shifrut E, Cortez JT, Skartsis N, Nguyen VQ, Woo JM, Roth TL, Yu R, Nguyen MLT, Simeonov DR, Nguyen DN, Targ S, Gate RE, Tang Q, Bluestone JA, Spitzer MH, Ye CJ, Marson A. Functional CRISPR dissection of gene networks controlling human regulatory T cell identity. Nat Immunol. 2020 11; 21(11):1456-1466.  View on PubMed
  12. Bluestone JA, Anderson M. Tolerance in the Age of Immunotherapy. N Engl J Med. 2020 09 17; 383(12):1156-1166.  View on PubMed
  13. Su Y, Chen D, Lausted C, Yuan D, Choi J, Dai C, Voillet V, Scherler K, Troisch P, Duvvuri VR, Baloni P, Qin G, Smith B, Kornilov S, Rostomily C, Xu A, Li J, Dong S, Rothchild A, Zhou J, Murray K, Edmark R, Hong S, Jones L, Zhou Y, Roper R, Mackay S, O'Mahony DS, Dale CR, Wallick JA, Algren HA, Michael ZA, Magis A, Wei W, Price ND, Huang S, Subramanian N, Wang K, Hadlock J, Hood L, Aderem A, Bluestone JA, Lanier LL, Greenberg P, Gottardo R, Davis MM, Goldman JD, Heath JR. Multiomic Immunophenotyping of COVID-19 Patients Reveals Early Infection Trajectories. bioRxiv. 2020 Jul 31.  View on PubMed
  14. Sawitzki B, Harden PN, Reinke P, Moreau A, Hutchinson JA, Game DS, Tang Q, Guinan EC, Battaglia M, Burlingham WJ, Roberts ISD, Streitz M, Josien R, Böger CA, Scottà C, Markmann JF, Hester JL, Juerchott K, Braudeau C, James B, Contreras-Ruiz L, van der Net JB, Bergler T, Caldara R, Petchey W, Edinger M, Dupas N, Kapinsky M, Mutzbauer I, Otto NM, Öllinger R, Hernandez-Fuentes MP, Issa F, Ahrens N, Meyenberg C, Karitzky S, Kunzendorf U, Knechtle SJ, Grinyó J, Morris PJ, Brent L, Bushell A, Turka LA, Bluestone JA, Lechler RI, Schlitt HJ, Cuturi MC, Schlickeiser S, Friend PJ, Miloud T, Scheffold A, Secchi A, Crisalli K, Kang SM, Hilton R, Banas B, Blancho G, Volk HD, Lombardi G, Wood KJ, Geissler EK. Regulatory cell therapy in kidney transplantation (The ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials. Lancet. 2020 05 23; 395(10237):1627-1639.  View on PubMed
  15. Cortez JT, Montauti E, Shifrut E, Gatchalian J, Zhang Y, Shaked O, Xu Y, Roth TL, Simeonov DR, Zhang Y, Chen S, Li Z, Woo JM, Ho J, Vogel IA, Prator GY, Zhang B, Lee Y, Sun Z, Ifergan I, Van Gool F, Hargreaves DC, Bluestone JA, Marson A, Fang D. CRISPR screen in regulatory T cells reveals modulators of Foxp3. Nature. 2020 06; 582(7812):416-420.  View on PubMed
  16. Roth TL, Li PJ, Blaeschke F, Nies JF, Apathy R, Mowery C, Yu R, Nguyen MLT, Lee Y, Truong A, Hiatt J, Wu D, Nguyen DN, Goodman D, Bluestone JA, Ye CJ, Roybal K, Shifrut E, Marson A. Pooled Knockin Targeting for Genome Engineering of Cellular Immunotherapies. Cell. 2020 04 30; 181(3):728-744.e21.  View on PubMed
  17. Stewart MD, Keane A, Butterfield LH, Levine BL, Thompson B, Xu Y, Ramsborg C, Lee A, Kalos M, Koerner C, Moore T, Markovic I, Lasiter L, Ibrahim R, Bluestone J, Sigal E, Allen J. Accelerating the development of innovative cellular therapy products for the treatment of cancer. Cytotherapy. 2020 05; 22(5):239-246.  View on PubMed
  18. Mufazalov IA, Andruszewski D, Schelmbauer C, Heink S, Blanfeld M, Masri J, Tang Y, Schüler R, Eich C, Wunderlich FT, Karbach SH, Bluestone JA, Korn T, Waisman A. Cutting Edge: IL-6-Driven Immune Dysregulation Is Strictly Dependent on IL-6R a-Chain Expression. J Immunol. 2020 02 15; 204(4):747-751.  View on PubMed
  19. Warshauer JT, Bluestone JA, Anderson MS. New Frontiers in the Treatment of Type 1 Diabetes. Cell Metab. 2020 01 07; 31(1):46-61.  View on PubMed
  20. Nguyen DN, Roth TL, Li PJ, Chen PA, Apathy R, Mamedov MR, Vo LT, Tobin VR, Goodman D, Shifrut E, Bluestone JA, Puck JM, Szoka FC, Marson A. Polymer-stabilized Cas9 nanoparticles and modified repair templates increase genome editing efficiency. Nat Biotechnol. 2020 01; 38(1):44-49.  View on PubMed

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