Kevan M. Shokat, PhD

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Kevan M. Shokat, PhD

Professor and Chair, Department of Cellular and Molecular Pharmacology, UCSF; Professor, Department of Chemistry, UC Berkeley; Investigator, Howard Hughes Medical Institute

kevan.shokat@ucsf.edu

Phone: (415) 514-0472 (voice)
Box 2280, UCSF
San Francisco, CA 94143-2280

UCSF Profiles | Lab Website

Research Summary

Research in my laboratory is focused on the discovery of new chemical based tools to decipher cellular signaling networks with an emphasis on protein kinases and more recently, GTPases. The analysis of signal transduction pathways has proven challenging using the traditional tools of biochemistry, genetics, and chemistry. Biochemical approaches are often limited in utility because signaling networks span from the cell surface to the control of transcription and translation, confounding reconstitution efforts from purified proteins. Genetic approaches allow specific perturbation of single components in an intact cell or organism, yet are often confounded by the emergent properties of signaling cascades. Chemical and pharmacological approaches enable rapid, reversible, and graded (dose-dependent) inactivation of single components in intact cells or organisms. Unfortunately, highly selective chemical probes (agonists, antagonists, traceable substrates, etc.) of protein kinases are difficult to develop because the 500 protein kinases share highly homologous ATP binding pockets. My laboratory has solved this fundamental problem for the largest family of enzymes in the human genome, protein kinases, by development of a strategy based on a combination of protein engineering and organic synthesis. We have termed this approach chemical genetics.

Education

Reed College (Portland, Oregon), B.A., 1986, Chemistry
UC Berkeley (Berkeley, California), Ph.D., 1991, Organic Chemistry


Professional Experience

  • 1986-1991
    (Advisor: Prof. Peter G. Schultz, UC Berkeley): Design and synthesis of haptens for the generation of catalytic antibodies. Thesis Title: New Routes to Catalytic Antibodies.
  • 1992-1994
    (Advisor: Prof. Christopher C. Goodnow, Stanford University): Investigation of mechanisms of immune self-tolerance in transgenic mice.
  • 1994-1998
    Assistant Professor of Chemistry and Molecular Biology, Princeton University
  • 1998-1999
    Associate Professor of Chemistry and Molecular Biology, Princeton University
  • 1999-2002
    Associate Professor of Cellular and Molecular Pharmacology, University of California, San Francisco
  • 1999-2002
    Associate Professor of Chemistry, University of California, Berkeley
  • 2001-present
    Professor of Cellular and Molecular Pharmacology, University of California, San Francisco
  • 2002-present
    Professor of Chemistry, University of California, Berkeley
  • 2004-present
    Vice-Chairman of Cellular and Molecular Pharmacology, UCSF
  • 2004-present
    Investigator, Howard Hughes Medical Institute

Honors & Awards

  • 1986
    Phi Beta Kappa - Reed College
  • 1986-1987
    UC Berkeley Regents Fellowship
  • 1989-1990
    UC Berkeley University Fellowship
  • 1992-1994
    Life Sciences Research Foundation Postdoctoral Fellow
  • 1995-1997
    NSF Early Career Development Award
  • 1996-2000
    Pew Scholar in the Biomedical Sciences
  • 1997-1998
    Glaxo-Wellcome Scholar in Organic Chemistry
  • 1997-2000
    Searle Scholar
  • 1997-2000
    Cottrell Scholar
  • 1999-2001
    Alfred P. Sloan Research Fellow
  • 2001
    Protein Society Young Investigator Award
  • 2002
    Eli Lilly Award in Biological Chemistry

Selected Publications

  1. Hoppmann C, Wong A, Yang B, Li S, Hunter T, Shokat KM, Wang L. Site-specific incorporation of phosphotyrosine using an expanded genetic code. Nat Chem Biol. 2017 Jun 12.
    View on PubMed
  2. Orr AL, Rutaganira FU, de Roulet D, Huang EJ, Hertz NT, Shokat KM, Nakamura K. Long-term oral kinetin does not protect against α-synuclein-induced neurodegeneration in rodent models of Parkinson's disease. Neurochem Int. 2017 Apr 20.
    View on PubMed
  3. Fan Q, Aksoy O, Wong RA, Ilkhanizadeh S, Novotny CJ, Gustafson WC, Truong AY, Cayanan G, Simonds EF, Haas-Kogan D, Phillips JJ, Nicolaides T, Okaniwa M, Shokat KM, Weiss WA. A Kinase Inhibitor Targeted to mTORC1 Drives Regression in Glioblastoma. Cancer Cell. 2017 Mar 13; 31(3):424-435.
    View on PubMed
  4. Urisman A, Levin RS, Gordan JD, Webber JT, Hernandez H, Ishihama Y, Shokat KM, Burlingame AL. An optimized chromatographic strategy for multiplexing in parallel reaction monitoring mass spectrometry: Insights from quantitation of activated kinases. Mol Cell Proteomics. 2016 Dec 11.
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  5. Uchida Y, Rutaganira FU, Jullie D, Shokat KM, von Zastrow M. Endosomal phosphatidylinositol 3-kinase is essential for canonical GPCR signaling. Mol Pharmacol. 2016 Nov 7.
    View on PubMed
  6. Lazarus MB, Levin RS, Shokat KM. Discovery of new substrates of the elongation factor-2 kinase suggests a broader role in the cellular nutrient response. Cell Signal. 2016 Oct 17; 29:78-83.
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  7. Kostic M, Crews CM, Hertweck C, Shokat K, Suga H. From Powerful Review Articles to Research Breakthroughs. Cell Chem Biol. 2016 Aug 18; 23(8):883-4.
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  8. Jo A, Choi TG, Jo YH, Jyothi KR, Nguyen MN, Kim JH, Lim S, Shahid M, Akter S, Lee S, Lee KH, Kim W, Cho H, Lee J, Shokat KM, Yoon KS, Kang I, Ha J, Kim SS. Inhibition of Carbonyl Reductase 1 Safely Improves the Efficacy of Doxorubicin in Breast Cancer Treatment. Antioxid Redox Signal. 2017 Jan 10; 26(2):70-83.
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  9. Levin RS, Hertz NT, Burlingame AL, Shokat KM, Mukherjee S. Innate immunity kinase TAK1 phosphorylates Rab1 on a hotspot for posttranslational modifications by host and pathogen. Proc Natl Acad Sci U S A. 2016 Aug 1.
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  10. Ostrem JM, Shokat KM. Direct small-molecule inhibitors of KRAS: from structural insights to mechanism-based design. Nat Rev Drug Discov. 2016 Nov; 15(11):771-785.
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  11. Miller RE, Brough R, Bajrami I, Williamson CT, McDade S, Campbell J, Kigozi A, Rafiq R, Pemberton H, Natrajan R, Joel J, Astley H, Mahoney C, Moore JD, Torrance C, Gordan JD, Webber JT, Levin RS, Shokat KM, Bandyopadhyay S, Lord CJ, Ashworth A. Synthetic Lethal Targeting of ARID1A-Mutant Ovarian Clear Cell Tumors with Dasatinib. Mol Cancer Ther. 2016 Jul; 15(7):1472-84.
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  12. Saha SK, Gordan JD, Kleinstiver BP, Vu P, Najem MS, Yeo JC, Shi L, Kato Y, Levin RS, Webber JT, Damon LJ, Egan RK, Greninger P, McDermott U, Garnett MJ, Jenkins RL, Rieger-Christ KM, Sullivan TB, Hezel AF, Liss AS, Mizukami Y, Goyal L, Ferrone CR, Zhu AX, Joung JK, Shokat KM, Benes CH, Bardeesy N. Isocitrate Dehydrogenase Mutations Confer Dasatinib Hypersensitivity and SRC Dependence in Intrahepatic Cholangiocarcinoma. Cancer Discov. 2016 Jul; 6(7):727-39.
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  13. Rodrik-Outmezguine VS, Okaniwa M, Yao Z, Novotny CJ, McWhirter C, Banaji A, Won H, Wong W, Berger M, de Stanchina E, Barratt DG, Cosulich S, Klinowska T, Rosen N, Shokat KM. Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor. Nature. 2016 Jun 9; 534(7606):272-6.
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  14. Tabaei SR, Guo F, Rutaganira FU, Vafaei S, Choong I, Shokat KM, Glenn JS, Cho NJ. Multistep Compositional Remodeling of Supported Lipid Membranes by Interfacially Active Phosphatidylinositol Kinases. Anal Chem. 2016 May 17; 88(10):5042-5.
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  15. Lee JK, Phillips JW, Smith BA, Park JW, Stoyanova T, McCaffrey EF, Baertsch R, Sokolov A, Meyerowitz JG, Mathis C, Cheng D, Stuart JM, Shokat KM, Gustafson WC, Huang J, Witte ON. N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells. Cancer Cell. 2016 Apr 11; 29(4):536-47.
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  16. Kostic M, Crews CM, Hertweck C, Shokat K, Suga H. Our Advisors, Our Ambassadors, Our Editorial Board Members. Cell Chem Biol. 2016 Mar 17; 23(3):311-2.
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  17. Rutaganira FU, Fowler ML, McPhail JA, Gelman MA, Nguyen K, Xiong A, Dornan GL, Tavshanjian B, Glenn JS, Shokat KM, Burke JE. Design and Structural Characterization of Potent and Selective Inhibitors of Phosphatidylinositol 4 Kinase IIIß. J Med Chem. 2016 Mar 10; 59(5):1830-9.
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  18. Kostic M, Crews CM, Hertweck C, Shokat K, Suga H. Voices of Chemical Biology: Charting the Next Decade. Cell Chem Biol. 2016 Feb 18; 23(2):199.
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  19. Fowler ML, McPhail JA, Jenkins ML, Masson GR, Rutaganira FU, Shokat KM, Williams RL, Burke JE. Using hydrogen deuterium exchange mass spectrometry to engineer optimized constructs for crystallization of protein complexes: Case study of PI4KIIIß with Rab11. Protein Sci. 2016 Apr; 25(4):826-39.
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  20. Kostic M, Crews CM, Hertweck C, Shokat K, Suga H. Cell Chemical Biology: Home of Exciting Chemical Biology. Cell Chem Biol. 2016 Jan 21; 23(1):1-2.
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