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

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. Boyce JH, Dang B, Ary B, Edmondson Q, Craik CS, DeGrado WF, Seiple IB. Platform to Discover Protease-Activated Antibiotics and Application to Siderophore-Antibiotic Conjugates. J Am Chem Soc. 2020 Dec 10.
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  2. Miller-Vedam LE, Bräuning B, Popova KD, Schirle Oakdale NT, Bonnar JL, Prabu JR, Boydston EA, Sevillano N, Shurtleff MJ, Stroud RM, Craik CS, Schulman BA, Frost A, Weissman JS. Structural and mechanistic basis of the EMC-dependent biogenesis of distinct transmembrane clients. Elife. 2020 Nov 25; 9.
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  3. Sevillano N, Bohn MF, Zimanyi M, Chen Y, Petzold C, Gupta S, Ralston CY, Craik CS. Structure of an affinity-matured inhibitory recombinant fab against urokinase plasminogen activator reveals basis of potency and specificity. Biochim Biophys Acta Proteins Proteom. 2020 Nov 19; 140562.
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  4. Lohse MB, Brenes LR, Ziv N, Winter MB, Craik CS, Johnson AD. An Opaque Cell-Specific Expression Program of Secreted Proteases and Transporters Allows Cell-Type Cooperation in Candida albicans. Genetics. 2020 Oct; 216(2):409-429.
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  5. Wei J, Wang YH, Lee CY, Truillet C, Oh DY, Xu Y, Ruggero D, Flavell RR, VanBrocklin HF, Seo Y, Craik CS, Fong L, Wang CI, Evans MJ. An Analysis of Isoclonal Antibody Formats Suggests a Role for Measuring PD-L1 with Low Molecular Weight PET Radiotracers. Mol Imaging Biol. 2020 12; 22(6):1553-1561.
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  6. Cogan DP, Li X, Sevillano N, Mathews II, Matsui T, Craik CS, Khosla C. Antibody Probes of Module 1 of the 6-Deoxyerythronolide B Synthase Reveal an Extended Conformation During Ketoreduction. J Am Chem Soc. 2020 Sep 02; 142(35):14933-14939.
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  7. Wang B, Asarnow D, Lee WH, Huang CW, Faust B, Ng PML, Ngoh EZX, Bohn M, Bulkley D, Pizzorno A, Tan HC, Lee CY, Minhat RA, Terrier O, Soh MK, Teo FJ, Yeap YYC, Hu Y, Seah SGK, Maurer-Stroh S, Renia L, Hanson BJ, Rosa-Calatrava M, Manglik A, Cheng Y, Craik CS, Wang CI. Bivalent binding of a fully human IgG to the SARS-CoV-2 spike proteins reveals mechanisms of potent neutralization. bioRxiv. 2020 Jul 15.
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  8. Lohse MB, Gulati M, Craik CS, Johnson AD, Nobile CJ. Combination of Antifungal Drugs and Protease Inhibitors Prevent Candida albicans Biofilm Formation and Disrupt Mature Biofilms. Front Microbiol. 2020; 11:1027.
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  9. Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL, Tummino TA, Hüttenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, Modak M, Kim M, Haas P, Polacco BJ, Braberg H, Fabius JM, Eckhardt M, Soucheray M, Bennett MJ, Cakir M, McGregor MJ, Li Q, Meyer B, Roesch F, Vallet T, Mac Kain A, Miorin L, Moreno E, Naing ZZC, Zhou Y, Peng S, Shi Y, Zhang Z, Shen W, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Barrio-Hernandez I, Memon D, Hernandez-Armenta C, Lyu J, Mathy CJP, Perica T, Pilla KB, Ganesan SJ, Saltzberg DJ, Rakesh R, Liu X, Rosenthal SB, Calviello L, Venkataramanan S, Liboy-Lugo J, Lin Y, Huang XP, Liu Y, Wankowicz SA, Bohn M, Safari M, Ugur FS, Koh C, Savar NS, Tran QD, Shengjuler D, Fletcher SJ, O'Neal MC, Cai Y, Chang JCJ, Broadhurst DJ, Klippsten S, Sharp PP, Wenzell NA, Kuzuoglu-Ozturk D, Wang HY, Trenker R, Young JM, Cavero DA, Hiatt J, Roth TL, Rathore U, Subramanian A, Noack J, Hubert M, Stroud RM, Frankel AD, Rosenberg OS, Verba KA, Agard DA, Ott M, Emerman M, Jura N, von Zastrow M, Verdin E, Ashworth A, Schwartz O, d'Enfert C, Mukherjee S, Jacobson M, Malik HS, Fujimori DG, Ideker T, Craik CS, Floor SN, Fraser JS, Gross JD, Sali A, Roth BL, Ruggero D, Taunton J, Kortemme T, Beltrao P, Vignuzzi M, García-Sastre A, Shokat KM, Shoichet BK, Krogan NJ. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020 07; 583(7816):459-468.
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  10. Vasiljeva O, Menendez E, Nguyen M, Craik CS, Michael Kavanaugh W. Monitoring protease activity in biological tissues using antibody prodrugs as sensing probes. Sci Rep. 2020 04 03; 10(1):5894.
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  11. Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, O'Meara MJ, Guo JZ, Swaney DL, Tummino TA, Hüttenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, Modak M, Kim M, Haas P, Polacco BJ, Braberg H, Fabius JM, Eckhardt M, Soucheray M, Bennett MJ, Cakir M, McGregor MJ, Li Q, Naing ZZC, Zhou Y, Peng S, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Shen W, Shi Y, Zhang Z, Barrio-Hernandez I, Memon D, Hernandez-Armenta C, Mathy CJP, Perica T, Pilla KB, Ganesan SJ, Saltzberg DJ, Ramachandran R, Liu X, Rosenthal SB, Calviello L, Venkataramanan S, Lin Y, Wankowicz SA, Bohn M, Trenker R, Young JM, Cavero D, Hiatt J, Roth T, Rathore U, Subramanian A, Noack J, Hubert M, Roesch F, Vallet T, Meyer B, White KM, Miorin L, Agard D, Emerman M, Ruggero D, García-Sastre A, Jura N, von Zastrow M, Taunton J, Schwartz O, Vignuzzi M, d'Enfert C, Mukherjee S, Jacobson M, Malik HS, Fujimori DG, Ideker T, Craik CS, Floor S, Fraser JS, Gross J, Sali A, Kortemme T, Beltrao P, Shokat K, Shoichet BK, Krogan NJ. A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing. bioRxiv. 2020 Mar 22.
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  12. Dvoráková H, Leontovyc R, Machácek T, O'Donoghue AJ, Šedo O, Zdráhal Z, Craik CS, Caffrey CR, Horák P, Mikeš L. Isoforms of Cathepsin B1 in Neurotropic Schistosomula of Trichobilharzia regenti Differ in Substrate Preferences and a Highly Expressed Catalytically Inactive Paralog Binds Cystatin. Front Cell Infect Microbiol. 2020; 10:66.
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  13. 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. 2020 01; 104(1):54-60.
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  14. 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 11 26; 400(12):1629-1638.
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  15. 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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  16. 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).
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  17. 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 10; 189(10):1916-1932.
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  18. 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 08; 15(8):786-794.
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  19. Basu K, Green EM, Cheng Y, Craik CS. Why recombinant antibodies - benefits and applications. Curr Opin Biotechnol. 2019 12; 60:153-158.
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  20. 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 03; 33(3):e13487.
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