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. 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, 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.  View on PubMed
  2. 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.  View on PubMed
  3. Bluestone JA, Tang Q Solving the Puzzle of Immune Tolerance for ß-Cell Replacement Therapy for Type 1 Diabetes.  View on PubMed
  4. 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.  View on PubMed
  5. Bluestone JA, Anderson M Tolerance in the Age of Immunotherapy.  View on PubMed
  6. 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.  View on PubMed
  7. 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.  View on PubMed
  8. 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.  View on PubMed
  9. 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.  View on PubMed
  10. 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.  View on PubMed
  11. 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.  View on PubMed
  12. Warshauer JT, Bluestone JA, Anderson MS New Frontiers in the Treatment of Type 1 Diabetes.  View on PubMed
  13. 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.  View on PubMed
  14. Raffin C, Vo LT, Bluestone JA Treg cell-based therapies: challenges and perspectives.  View on PubMed
  15. 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.  View on PubMed
  16. Ferreira LMR, Muller YD, Bluestone JA, Tang Q Next-generation regulatory T cell therapy.  View on PubMed
  17. 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.  View on PubMed
  18. Azimi CS, Tang Q, Roybal KT, Bluestone JA NextGen cell-based immunotherapies in cancer and other immune disorders.  View on PubMed
  19. 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.  View on PubMed
  20. 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.  View on PubMed

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