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

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. Ravalin M, Basu K, Gestwicki JE, Craik CS. End-Binding E3 Ubiquitin Ligases Enable Protease Signaling. ACS Chem Biol. 2019 Nov 20.
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  2. Harel ET, Drake PM, Barfield RM, Lui I, Farr-Jones S, Van't Veer L, Gartner ZJ, Green EM, Lourenço AL, Cheng Y, Hann BC, Rabuka D, Craik CS. Antibody-Drug Conjugates Targeting the Urokinase Receptor (uPAR) as a Possible Treatment of Aggressive Breast Cancer. Antibodies (Basel). 2019 Nov 05; 8(4).
    View on PubMed
  3. Harel E, Shoji J, Abraham V, Miller L, Laszik ZG, King A, Dobi D, Szabo G, Hann B, Sarwal MM, Craik CS, Vincenti F. Further Evidence that the Soluble Urokinase Plasminogen Activator Receptor Does Not Directly Injure Mice or Human Podocytes. Transplantation. 2019 Aug 19.
    View on PubMed
  4. Caiazza F, Oficjalska K, Tosetto M, Phelan JJ, Noonan S, Martin P, Killick K, Breen L, O'Neill F, Nolan B, Furney S, Power R, Fennelly D, Craik CS, O'Sullivan J, Sheahan K, Doherty GA, Ryan EJ. KH-Type Splicing Regulatory Protein Controls Colorectal Cancer Cell Growth and Modulates the Tumor Microenvironment. Am J Pathol. 2019 Oct; 189(10):1916-1932.
    View on PubMed
  5. Ivry SL, Knudsen GM, Caiazza F, Sharib JM, Jaradeh K, Ravalin M, O'Donoghue AJ, Kirkwood KS, Craik CS. The lysosomal aminopeptidase tripeptidyl peptidase 1 displays increased activity in malignant pancreatic cysts. Biol Chem. 2019 Jul 19.
    View on PubMed
  6. Ravalin M, Theofilas P, Basu K, Opoku-Nsiah KA, Assimon VA, Medina-Cleghorn D, Chen YF, Bohn MF, Arkin M, Grinberg LT, Craik CS, Gestwicki JE. Specificity for latent C termini links the E3 ubiquitin ligase CHIP to caspases. Nat Chem Biol. 2019 Aug; 15(8):786-794.
    View on PubMed
  7. Basu K, Green EM, Cheng Y, Craik CS. Why recombinant antibodies - benefits and applications. Curr Opin Biotechnol. 2019 Mar 05; 60:153-158.
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  8. Harel E, Shoji J, Abraham V, Miller L, Laszik Z, Thurison T, King A, Olshen A, Leung J, Szabo G, Hann B, Høyer-Hansen G, Craik CS, Vincenti F. Identifying a potential biomarker for primary focal segmental glomerulosclerosis and its association with recurrence after transplantation. Clin Transplant. 2019 Mar; 33(3):e13487.
    View on PubMed
  9. Butler VJ, Cortopassi WA, Argouarch AR, Ivry SL, Craik CS, Jacobson MP, Kao AW. Progranulin Stimulates the In Vitro Maturation of Pro-Cathepsin D at Acidic pH. J Mol Biol. 2019 Mar 01; 431(5):1038-1047.
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  10. Damalanka VC, Han Z, Karmakar P, O'Donoghue AJ, La Greca F, Kim T, Pant SM, Helander J, Klefström J, Craik CS, Janetka JW. Discovery of Selective Matriptase and Hepsin Serine Protease Inhibitors: Useful Chemical Tools for Cancer Cell Biology. J Med Chem. 2019 01 24; 62(2):480-490.
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  11. Schneidman-Duhovny D, Khuri N, Dong GQ, Winter MB, Shifrut E, Friedman N, Craik CS, Pratt KP, Paz P, Aswad F, Sali A. Predicting CD4 T-cell epitopes based on antigen cleavage, MHCII presentation, and TCR recognition. PLoS One. 2018; 13(11):e0206654.
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  12. Li X, Sevillano N, La Greca F, Hsu J, Mathews II, Matsui T, Craik CS, Khosla C. Discovery and Characterization of a Thioesterase-Specific Monoclonal Antibody That Recognizes the 6-Deoxyerythronolide B Synthase. Biochemistry. 2018 10 30; 57(43):6201-6208.
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  13. Moroz A, Lee CY, Wang YH, Hsiao JC, Sevillano N, Truillet C, Craik CS, Fong L, Wang CI, Evans MJ. A Preclinical Assessment of 89Zr-atezolizumab Identifies a Requirement for Carrier Added Formulations Not Observed with 89Zr-C4. Bioconjug Chem. 2018 10 17; 29(10):3476-3482.
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  14. Debela M, Magdolen V, Skala W, Elsässer B, Schneider EL, Craik CS, Biniossek ML, Schilling O, Bode W, Brandstetter H, Goettig P. Structural determinants of specificity and regulation of activity in the allosteric loop network of human KLK8/neuropsin. Sci Rep. 2018 Jul 16; 8(1):10705.
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  15. Li X, Sevillano N, La Greca F, Deis L, Liu YC, Deller MC, Mathews II, Matsui T, Cane DE, Craik CS, Khosla C. Structure-Function Analysis of the Extended Conformation of a Polyketide Synthase Module. J Am Chem Soc. 2018 05 30; 140(21):6518-6521.
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  16. Leontovyc A, Ulrychová L, O'Donoghue AJ, Vondrášek J, Marešová L, Hubálek M, Fajtová P, Chanová M, Jiang Z, Craik CS, Caffrey CR, Mareš M, Dvorák J, Horn M. SmSP2: A serine protease secreted by the blood fluke pathogen Schistosoma mansoni with anti-hemostatic properties. PLoS Negl Trop Dis. 2018 04; 12(4):e0006446.
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  17. Corvo I, Ferraro F, Merlino A, Zuberbühler K, O'Donoghue AJ, Pastro L, Pi-Denis N, Basika T, Roche L, McKerrow JH, Craik CS, Caffrey CR, Tort JF. Substrate Specificity of Cysteine Proteases Beyond the S2 Pocket: Mutagenesis and Molecular Dynamics Investigation of Fasciola hepatica Cathepsins L. Front Mol Biosci. 2018; 5:40.
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  18. Binning JM, Smith AM, Hultquist JF, Craik CS, Caretta Cartozo N, Campbell MG, Burton L, La Greca F, McGregor MJ, Ta HM, Bartholomeeusen K, Peterlin BM, Krogan NJ, Sevillano N, Cheng Y, Gross JD. Fab-based inhibitors reveal ubiquitin independent functions for HIV Vif neutralization of APOBEC3 restriction factors. PLoS Pathog. 2018 01; 14(1):e1006830.
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  19. Dang S, Feng S, Tien J, Peters CJ, Bulkley D, Lolicato M, Zhao J, Zuberbühler K, Ye W, Qi L, Chen T, Craik CS, Jan YN, Minor DL, Cheng Y, Jan LY. Cryo-EM structures of the TMEM16A calcium-activated chloride channel. Nature. 2017 12 21; 552(7685):426-429.
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  20. Ivry SL, Meyer NO, Winter MB, Bohn MF, Knudsen GM, O'Donoghue AJ, Craik CS. Global substrate specificity profiling of post-translational modifying enzymes. Protein Sci. 2018 03; 27(3):584-594.
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