Lawrence Fong, MD

Lawrence Fong, MD

Professor, Department of Medicine (Hematology/Oncology), UCSF

Phone: (415) 353-7171 (appts)
Box 0511, UCSF
San Francisco, CA 94143-0511

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Research Summary

My lab is focused on structure function studies of nuclear receptors and transcription control proteins in stem cells. My lab uses biochemical and biophysical methods to evaluate protein complexes. Among the technologies employed are surface plasmon resonance, X-ray crystallography, and differential scanning fluorescence. Mutagenesis and cell assays are employed to gauge functional effects of mutagenesis to evaluate the hypotheses linking structure to function. We determined the first three-dimensional structure for any nuclear receptor and published papers on the thyroid hormone receptor, androgen receptor, and glucocorticoid receptor, as well as on LRH-1, SF-1, and Dax-1 receptors, and developed bait-affinity expression for making the first complex of a nuclear receptor with its corepressor. Research on androgen receptor interactions with peptides and small molecules helped define the specificity of the AF2 site and led to the discovery of a new protein binding site on the androgen receptor hormone binding domain.
My lab is known for determining structures of important protein molecules and assemblies, and relating structures to the mechanisms of function of the macromolecules. Many of the papers from the lab are recognized by experts as useful contributions to the field. Early papers from my lab were mostly on learning about allosteric control of enzyme catalysis. Using glycogen phosphorylase as the target, we determined the structure at high resolution for the phosphorylated dimer, normally active but inhibited by an allosteric effector. At about 200,000 molecular weight, this protein was the largest with known structure for about ten years. We also embraced recombinant DNA methods early. Ours was the first lab to clone all isozymes for any human protein. Our muscle cDNA library was used by others to clone challenging targets, including the first Ca ATPase. With expertise in cloning technologies, we were positioned to compare the regulation of glycogen phosphorylases in evolution from yeast to human. Recognition of my work on allostery was the basis for election to the National Academy of Sciences. Recently, our lab has focused on learning more about mechanisms of transcription factors, especially nuclear receptors. This focus led us to publish our first paper in cancer biology that identifies a potential target for treating pancreatic cancer.


Columbia University, New York, NY, BA, 1984-1988, Pre-Med., Economics
Stanford University, Stanford, CA, MD, 1988-1992

Professional Experience

  • 1992-1993
    Intern in Internal Medicine, University of Washington Medical Center.
  • 1993-1994
    Resident in Internal Medicine, University of Washington Medical Center.
  • 1994-1997
    Fellow in Medical Oncology, Stanford University School of Medicine.
  • 1996-2001
    Post-Doctoral Fellow, Department of Pathology, Stanford University School of Medicine. Mentor: Edgar Engleman, MD.
  • 1997-2002
    Staff Physician, Division of Medical Oncology, Stanford University School of Medicine.
  • 2001-2002
    Acting Assistant Professor, Department of Pathology, Stanford University School of Medicine. Mentor: Mark M. Davis, PhD
  • 2002-2008
    Assistant Professor in Residence, Department of Medicine, Division of Hematology/Oncology, University of California, San Francisco.
  • 2008-2013
    Associate Professor, Department of Medicine, Division of Hematology/Oncology, University of California, San Francisco.
  • 2013-present
    Professor, Department of Medicine, Division of Hematology/Oncology, University of California, San Francisco.


Honors & Awards

  • 1990
    Stanford Alumni Medical Scholar
  • 1993
    Alpha Omega Alpha
  • 1997
    American Society of Clinical Oncology Young Investigator Award
  • 1997
    American Cancer Society Post-Doctoral Fellowship Award
  • 1997
    American Association for Cancer Research AFLAC Award
  • 2002
    American Association for Cancer Research Scholar-in-Training Award
  • 2003
    V Foundation Scholar

Selected Publications

  1. Wei XX, Fong L, Small EJ. Prostate Cancer Immunotherapy with Sipuleucel-T: Current Standards and Future Directions. Expert Rev Vaccines. 2015 Dec; 14(12):1529-41.
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  2. Oh DY, Venook AP, Fong L. On the Verge: Immunotherapy for Colorectal Carcinoma. J Natl Compr Canc Netw. 2015 Aug; 13(8):970-8.
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  3. Landegren N, Sharon D, Shum AK, Khan IS, Fasano KJ, Hallgren Å, Kampf C, Freyhult E, Ardesjö-Lundgren B, Alimohammadi M, Rathsman S, Ludvigsson JF, Lundh D, Motrich R, Rivero V, Fong L, Giwercman A, Gustafsson J, Perheentupa J, Husebye ES, Anderson MS, Snyder M, Kämpe O. Transglutaminase 4 as a prostate autoantigen in male subfertility. Sci Transl Med. 2015 Jun 17; 7(292):292ra101.
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  4. Kwek SS, Lewis J, Zhang L, Weinberg V, Greaney SK, Harzstark AL, Lin AM, Ryan CJ, Small EJ, Fong L. Preexisting Levels of CD4 T Cells Expressing PD-1 Are Related to Overall Survival in Prostate Cancer Patients Treated with Ipilimumab. Cancer Immunol Res. 2015 Sep; 3(9):1008-16.
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  5. Small EJ, Lance RS, Gardner TA, Karsh LI, Fong L, McCoy C, DeVries T, Sheikh NA, GuhaThakurta D, Chang N, Redfern CH, Shore ND. A Randomized Phase II Trial of Sipuleucel-T with Concurrent versus Sequential Abiraterone Acetate plus Prednisone in Metastatic Castration-Resistant Prostate Cancer. Clin Cancer Res. 2015 Sep 1; 21(17):3862-9.
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  6. Kim W, Zhang L, Wilton JH, Fetterly G, Mohler JL, Weinberg V, Morse A, Szmulewitz RZ, Friedlander TW, Fong L, Lin AM, Harzstark AL, Molina A, Small EJ, Ryan CJ. Sequential use of the androgen synthesis inhibitors ketoconazole and abiraterone acetate in castration-resistant prostate cancer and the predictive value of circulating androgens. Clin Cancer Res. 2014 Dec 15; 20(24):6269-76.
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  7. Fong L, Carroll P, Weinberg V, Chan S, Lewis J, Corman J, Amling CL, Stephenson RA, Simko J, Sheikh NA, Sims RB, Frohlich MW, Small EJ. Activated lymphocyte recruitment into the tumor microenvironment following preoperative sipuleucel-T for localized prostate cancer. J Natl Cancer Inst. 2014 Nov; 106(11).
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  8. Cha E, Klinger M, Hou Y, Cummings C, Ribas A, Faham M, Fong L. Improved survival with T cell clonotype stability after anti-CTLA-4 treatment in cancer patients. Sci Transl Med. 2014 May 28; 6(238):238ra70.
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  9. Khan IS, Mouchess ML, Zhu ML, Conley B, Fasano KJ, Hou Y, Fong L, Su MA, Anderson MS. Enhancement of an anti-tumor immune response by transient blockade of central T cell tolerance. J Exp Med. 2014 May 5; 211(5):761-8.
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  10. Friedlander TW, Fong L. The end of the beginning: circulating tumor cells as a biomarker in castration-resistant prostate cancer. J Clin Oncol. 2014 Apr 10; 32(11):1104-6.
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  11. Cheng ML, Fong L. Beyond sipuleucel-T: immune approaches to treating prostate cancer. Curr Treat Options Oncol. 2014 Mar; 15(1):115-26.
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  12. Cheng ML, Fong L. Effects of RANKL-Targeted Therapy in Immunity and Cancer. Front Oncol. 2014 Jan 7; 3:329.
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  13. Kwek SS, Dao V, Roy R, Hou Y, Alajajian D, Simko JP, Small EJ, Fong L. Diversity of antigen-specific responses induced in vivo with CTLA-4 blockade in prostate cancer patients. J Immunol. 2012 Oct 1; 189(7):3759-66.
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  14. Kwek SS, Cha E, Fong L. Unmasking the immune recognition of prostate cancer with CTLA4 blockade. Nat Rev Cancer. 2012 Apr; 12(4):289-97.
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  15. Taccioli C, Chen H, Jiang Y, Liu XP, Huang K, Smalley KJ, Farber JL, Croce CM, Fong LY. Dietary zinc deficiency fuels esophageal cancer development by inducing a distinct inflammatory signature. Oncogene. 2012 Oct 18; 31(42):4550-8.
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  16. Friedlander TW, Weinberg VK, Huang Y, Mi JT, Formaker CG, Small EJ, Harzstark AL, Lin AM, Fong L, Ryan CJ. A phase II study of insulin-like growth factor receptor inhibition with nordihydroguaiaretic acid in men with non-metastatic hormone-sensitive prostate cancer. Oncol Rep. 2012 Jan; 27(1):3-9.
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  17. Cha E, Fong L. Immunotherapy for prostate cancer: biology and therapeutic approaches. J Clin Oncol. 2011 Sep 20; 29(27):3677-85.
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  18. Kapadia D, Sadikovic A, Vanloubbeeck Y, Brockstedt D, Fong L. Interplay between CD8a+ dendritic cells and monocytes in response to Listeria monocytogenes infection attenuates T cell responses. PLoS One. 2011; 6(4):e19376.
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  19. Harzstark AL, Small EJ, Weinberg VK, Sun J, Ryan CJ, Lin AM, Fong L, Brocks DR, Rosenberg JE. A phase 1 study of everolimus and sorafenib for metastatic clear cell renal cell carcinoma. Cancer. 2011 Sep 15; 117(18):4194-200.
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  20. Posselt AM, Szot GL, Frassetto LA, Masharani U, Tavakol M, Amin R, McElroy J, Ramos MD, Kerlan RK, Fong L, Vincenti F, Bluestone JA, Stock PG. Islet transplantation in type 1 diabetic patients using calcineurin inhibitor-free immunosuppressive protocols based on T-cell adhesion or costimulation blockade. Transplantation. 2010 Dec 27; 90(12):1595-601.
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