University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Charles S. Craik, PhD

Charles S. Craik, PhD

Professor, Departments of Pharmaceutical Chemistry, Pharmacology, and Biochemistry/Biophysics, UCSF; Co-Leader, Experimental Therapeutics Program, Helen Diller Family Comprehensive Cancer Center

Cancer Center Program Memberships

Prostate Cancer | Experimental Therapeutics

Research Summary

The research interests of my lab focus on defining the roles and the mechanisms of enzymes in complex biological processes and on developing technologies to facilitate these studies. Information on my lab can be found at the following website: http://www.craiklab.ucsf.edu/. The primary emphasis of our work has been on enzymes, with a particular emphasis on macromolecular recognition. Our original protein engineering studies have evolved to encompass various proteases as well as their endogenous inhibitors and membrane bound receptors, including uPAR, and have recently been successful at developing functional imaging probes for breast, colon, and prostate cancer using novel technologies. Our antibody engineering studies have identified Fabs that recognize conformational states of the target enzyme or receptor and are being developed into functional probes for in vivo imaging. The methodologies we developed to identify these functional Fabs have also been applied to enzymes and membrane proteins for structural and functional studies.

Education

Allegheny College, Meadville, PA, B.S., 1976, Chemistry
Columbia University, N.Y., NY, M.A., 1978, Chemistry
Columbia University, N.Y., NY, Ph.D., 1981, Chemistry


Professional Experience

  • 1981-85
    Postgraduate Research Biochemist, Department of Biochemistry & Biophysics, UCSF
  • 1985-91
    Assistant Professor, Departments of Pharm. Chemistry and Biochemistry & Biophysics, UCSF
  • 1991-1994
    Associate Professor, Departments of Pharm. Chemistry and Biochemistry & Biophysics, UCSF
  • 1994-present
    Professor, Departments of Pharm. Chemistry, and Biochemistry & Biophysics, UCSF
  • 1995-present
    Professor, Departments of Pharm. Chemistry, Pharmacology and Biochemistry & Biophysics, UCSF

Honors & Awards

  • 1972-75
    National Honor Society; Alden Scholar
  • 1974-75
    Doane Distinguished Scholar, Phi Beta Kappa
  • 1975
    Richard Edwin Lee Scholar
  • 1985-86
    Top 100 Innovators - Science Digest
  • 2013
    Institute Medal Lecture and Award, Institute of Organic Chemistry and Biochemistry, Academy of Sciences, Prague, Czech Republic
  • 2017
    elected to American Academy of Arts and Sciences

Selected Publications

  1. Kara E, Manna D, Løset GÅ, Schneider EL, Craik CS, Kanse S. Analysis of the substrate specificity of Factor VII activating protease (FSAP) and design of specific and sensitive peptide substrates. Thromb Haemost. 2017 Aug 30; 117(9):1750-1760.
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  2. Wilkinson DJ, Habgood A, Lamb HK, Thompson P, Hawkins AR, Désilets A, Leduc R, Steinmetzer T, Hammami M, Lee MS, Craik CS, Watson S, Lin H, Milner JM, Rowan AD. Matriptase Induction of Metalloproteinase-Dependent Aggrecanolysis In Vitro and In Vivo: Promotion of Osteoarthritic Cartilage Damage by Multiple Mechanisms. Arthritis Rheumatol. 2017 Aug; 69(8):1601-1611.
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  3. Roncase EJ, Moon C, Chatterjee S, González-Páez GE, Craik CS, O'Donoghue AJ, Wolan DW. Substrate Profiling and High Resolution Co-complex Crystal Structure of a Secreted C11 Protease Conserved across Commensal Bacteria. ACS Chem Biol. 2017 Jun 16; 12(6):1556-1565.
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  4. Ivry SL, Sharib JM, Dominguez DA, Roy N, Hatcher SE, Yip-Schneider M, Schmidt CM, Brand RE, Park WG, Hebrok M, Kim G, O'Donoghue AJ, Kirkwood KS, Craik CS. Global protease activity profiling provides differential diagnosis of pancreatic cysts. Clin Cancer Res. 2017 Apr 19.
    View on PubMed
  5. Lourenço AL, Salvador RRS, Silva LA, Saito MS, Mello JFR, Cabral LM, Rodrigues CR, Vera MAF, Muri EMF, de Souza AMT, Craik CS, Dias LRS, Castro HC, Sathler PC. Synthesis and mechanistic evaluation of novel N'-benzylidene-carbohydrazide-1H-pyrazolo[3,4-b]pyridine derivatives as non-anionic antiplatelet agents. Eur J Med Chem. 2017 Jul 28; 135:213-229.
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  6. Meyer NO, O'Donoghue AJ, Schulze-Gahmen U, Ravalin M, Moss SM, Winter MB, Knudsen GM, Craik CS. Multiplex Substrate Profiling by Mass Spectrometry for Kinases Reveals Quantitative Substrate Motifs. Anal Chem. 2017 Mar 21.
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  7. Guo CJ, Chang FY, Wyche TP, Backus KM, Acker TM, Funabashi M, Taketani M, Donia MS, Nayfach S, Pollard KS, Craik CS, Cravatt BF, Clardy J, Voigt CA, Fischbach MA. Discovery of Reactive Microbiota-Derived Metabolites that Inhibit Host Proteases. Cell. 2017 Jan 26; 168(3):517-526.e18.
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  8. Clarke SC, Dumesic PA, Homer CM, O'Donoghue AJ, La Greca F, Pallova L, Majer P, Madhani HD, Craik CS. Integrated Activity and Genetic Profiling of Secreted Peptidases in Cryptococcus neoformans Reveals an Aspartyl Peptidase Required for Low pH Survival and Virulence. PLoS Pathog. 2016 Dec; 12(12):e1006051.
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  9. Barkan DT, Cheng XL, Celino H, Tran TT, Bhandari A, Craik CS, Sali A, Smythe ML. Clustering of disulfide-rich peptides provides scaffolds for hit discovery by phage display: application to interleukin-23. BMC Bioinformatics. 2016 Nov 23; 17(1):481.
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  10. Winter MB, Salcedo EC, Lohse MB, Hartooni N, Gulati M, Sanchez H, Takagi J, Hube B, Andes DR, Johnson AD, Craik CS, Nobile CJ. Global Identification of Biofilm-Specific Proteolysis in Candida albicans. MBio. 2016; 7(5).
    View on PubMed
  11. O'Donoghue AJ, Ivry SL, Chaudhury C, Hostetter DR, Hanahan D, Craik CS. Procathepsin E is highly abundant but minimally active in pancreatic ductal adenocarcinoma tumors. Biol Chem. 2016 Sep 1; 397(9):871-81.
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  12. Goupil LS, Ivry SL, Hsieh I, Suzuki BM, Craik CS, O'Donoghue AJ, McKerrow JH. Cysteine and Aspartyl Proteases Contribute to Protein Digestion in the Gut of Freshwater Planaria. PLoS Negl Trop Dis. 2016 Aug; 10(8):e0004893.
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  13. Duan C, Alibakhshi MA, Kim DK, Brown CM, Craik CS, Majumdar A. Label-Free Electrical Detection of Enzymatic Reactions in Nanochannels. ACS Nano. 2016 Aug 23; 10(8):7476-84.
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  14. Lentz CS, Ordonez AA, Kasperkiewicz P, La Greca F, O'Donoghue AJ, Schulze CJ, Powers JC, Craik CS, Drag M, Jain SK, Bogyo M. Design of Selective Substrates and Activity-Based Probes for Hydrolase Important for Pathogenesis 1 (HIP1) from Mycobacterium tuberculosis. ACS Infect Dis. 2016 Nov 11; 2(11):807-815.
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  15. Homer CM, Summers DK, Goranov AI, Clarke SC, Wiesner DL, Diedrich JK, Moresco JJ, Toffaletti D, Upadhya R, Caradonna I, Petnic S, Pessino V, Cuomo CA, Lodge JK, Perfect J, Yates JR, Nielsen K, Craik CS, Madhani HD. Intracellular Action of a Secreted Peptide Required for Fungal Virulence. Cell Host Microbe. 2016 Jun 8; 19(6):849-64.
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  16. Drake CR, Sevillano N, Truillet C, Craik CS, VanBrocklin HF, Evans MJ. Site-Specific Radiofluorination of Biomolecules with 8-[(18)F]-Fluorooctanoic Acid Catalyzed by Lipoic Acid Ligase. ACS Chem Biol. 2016 Jun 17; 11(6):1587-94.
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  17. Julien O, Zhuang M, Wiita AP, O'Donoghue AJ, Knudsen GM, Craik CS, Wells JA. Quantitative MS-based enzymology of caspases reveals distinct protein substrate specificities, hierarchies, and cellular roles. Proc Natl Acad Sci U S A. 2016 Apr 5; 113(14):E2001-10.
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  18. Li H, O'Donoghue AJ, van der Linden WA, Xie SC, Yoo E, Foe IT, Tilley L, Craik CS, da Fonseca PC, Bogyo M. Structure- and function-based design of Plasmodium-selective proteasome inhibitors. Nature. 2016 Feb 10; 530(7589):233-6.
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  19. Gable JE, Lee GM, Acker TM, Hulce KR, Gonzalez ER, Schweigler P, Melkko S, Farady CJ, Craik CS. Fragment-Based Protein-Protein Interaction Antagonists of a Viral Dimeric Protease. ChemMedChem. 2016 Apr 19; 11(8):862-9.
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  20. Bibo-Verdugo B, O'Donoghue AJ, Rojo-Arreola L, Craik CS, García-Carreño F. Complementary Proteomic and Biochemical Analysis of Peptidases in Lobster Gastric Juice Uncovers the Functional Role of Individual Enzymes in Food Digestion. Mar Biotechnol (NY). 2016 Apr; 18(2):201-14.
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