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

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Cancer Center Membership

Program Member » Developmental Therapeutics» Cancer Genetics

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. 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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  2. 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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  3. 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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  4. 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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  5. 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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  6. 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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  7. 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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  8. 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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  9. 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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  10. 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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  11. Sansó M, Levin RS, Lipp JJ, Wang VY, Greifenberg AK, Quezada EM, Ali A, Ghosh A, Larochelle S, Rana TM, Geyer M, Tong L, Shokat KM, Fisher RP. P-TEFb regulation of transcription termination factor Xrn2 revealed by a chemical genetic screen for Cdk9 substrates. Genes Dev. 2016 Jan 1; 30(1):117-31.
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  12. Floor SN, Barkovich KJ, Condon KJ, Shokat KM, Doudna JA. Analog sensitive chemical inhibition of the DEAD-box protein DDX3. Protein Sci. 2016 Mar; 25(3):638-49.
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  13. Kuhlenschmidt TB, Rutaganira FU, Long S, Tang K, Shokat KM, Kuhlenschmidt MS, Sibley LD. Inhibition of Calcium-Dependent Protein Kinase 1 (CDPK1) In Vitro by Pyrazolopyrimidine Derivatives Does Not Correlate with Sensitivity of Cryptosporidium parvum Growth in Cell Culture. Antimicrob Agents Chemother. 2015; 60(1):570-9.
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  14. Costa HA, Leitner MG, Sos ML, Mavrantoni A, Rychkova A, Johnson JR, Newton BW, Yee MC, De La Vega FM, Ford JM, Krogan NJ, Shokat KM, Oliver D, Halaszovich CR, Bustamante CD. Discovery and functional characterization of a neomorphic PTEN mutation. Proc Natl Acad Sci U S A. 2015 Oct 26.
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  15. Schaffer BE, Levin RS, Hertz NT, Maures TJ, Schoof ML, Hollstein PE, Benayoun BA, Banko MR, Shaw RJ, Shokat KM, Brunet A. Identification of AMPK Phosphorylation Sites Reveals a Network of Proteins Involved in Cell Invasion and Facilitates Large-Scale Substrate Prediction. Cell Metab. 2015 Nov 3; 22(5):907-21.
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  16. Manz BN, Tan YX, Courtney AH, Rutaganira F, Palmer E, Shokat KM, Weiss A. Small molecule inhibition of Csk alters affinity recognition by T cells. Elife. 2015; 4.
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  17. Lazarus MB, Shokat KM. Discovery and structure of a new inhibitor scaffold of the autophagy initiating kinase ULK1. Bioorg Med Chem. 2015 Sep 1; 23(17):5483-8.
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  18. Lipp JJ, Marvin MC, Shokat KM, Guthrie C. SR protein kinases promote splicing of nonconsensus introns. Nat Struct Mol Biol. 2015 Aug; 22(8):611-7.
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  19. Friedel P, Kahle KT, Zhang J, Hertz N, Pisella LI, Buhler E, Schaller F, Duan J, Khanna AR, Bishop PN, Shokat KM, Medina I. WNK1-regulated inhibitory phosphorylation of the KCC2 cotransporter maintains the depolarizing action of GABA in immature neurons. Sci Signal. 2015; 8(383):ra65.
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  20. Mendez AS, Alfaro J, Morales-Soto MA, Dar AC, McCullagh E, Gotthardt K, Li H, Acosta-Alvear D, Sidrauski C, Korennykh AV, Bernales S, Shokat KM, Walter P. Endoplasmic reticulum stress-independent activation of unfolded protein response kinases by a small molecule ATP-mimic. Elife. 2015; 4.
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