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.

Research Funding

  • July 1, 2002 - June 30, 2022 - Research Training in Chemistry and Chemical Biology, Principal Investigator. Sponsor: NIH/NIGMS, Sponsor Award ID: T32GM064337
  • August 1, 2015 - July 31, 2020 - Mapping the conformational cycle of transmembrane transporters, Co-Investigator. Sponsor: NIH/NIGMS, Sponsor Award ID: P01GM111126
  • September 24, 2014 - August 31, 2019 - Antibody Research Technology Center, Co-Investigator. Sponsor: NIH/NCI, Sponsor Award ID: P41CA196276
  • July 10, 2013 - March 31, 2017 - Allosteric Inhibition of a Family of Proteolytic Enzymes, Principal Investigator. Sponsor: NIH/NIGMS, Sponsor Award ID: R01GM104659

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. Kryštufek R, Šácha P, Starková J, Brynda J, Hradilek M, Tloušt'ová E, Grzymska J, Rut W, Boucher MJ, Drag M, Majer P, Hájek M, Rezácová P, Madhani HD, Craik CS, Konvalinka J. Re-emerging Aspartic Protease Targets: Examining Cryptococcus neoformans Major Aspartyl Peptidase 1 as a Target for Antifungal Drug Discovery. J Med Chem. 2021 May 27; 64(10):6706-6719.  View on PubMed
  2. Sevillano N, Green EM, Votteler J, Kim DY, Ren X, Yang B, Liu X, Lourenço AL, Hurley JH, Farr-Jones S, Gross JD, Cheng Y, Craik CS. Identification of recombinant Fabs for structural and functional characterization of HIV-host factor complexes. PLoS One. 2021; 16(5):e0250318.  View on PubMed
  3. Ravalin M, Craik CS. Beginning at the End(s): A Latent End-Binding Network at the Host-Pathogen Interface. Biochemistry. 2021 May 10.  View on PubMed
  4. Mahoney M, Damalanka VC, Tartell MA, Chung DH, Lourenco AL, Pwee D, Mayer Bridwell AE, Hoffmann M, Voss J, Karmakar P, Azouz N, Klingler AM, Rothlauf PW, Thompson CE, Lee M, Klampfer L, Stallings C, Rothenberg ME, Pöhlmann S, Whelan SP, O'Donoghue AJ, Craik CS, Janetka JW. A novel class of TMPRSS2 inhibitors potently block SARS-CoV-2 and MERS-CoV viral entry and protect human epithelial lung cells. bioRxiv. 2021 May 06.  View on PubMed
  5. Asarnow D, Wang B, Lee WH, Hu Y, Huang CW, Faust B, Ng PML, Ngoh EZX, Bohn M, Bulkley D, Pizzorno A, Ary B, Tan HC, Lee CY, Minhat RA, Terrier O, Soh MK, Teo FJ, Yeap YYC, Seah SGK, Chan CEZ, Connelly E, Young NJ, Maurer-Stroh S, Renia L, Hanson BJ, Rosa-Calatrava M, Manglik A, Cheng Y, Craik CS, Wang CI. Structural insight into SARS-CoV-2 neutralizing antibodies and modulation of syncytia. Cell. 2021 Apr 24.  View on PubMed
  6. Salcedo EC, Winter MB, Khuri N, Knudsen GM, Sali A, Craik CS. Global Protease Activity Profiling Identifies HER2-Driven Proteolysis in Breast Cancer. ACS Chem Biol. 2021 04 16; 16(4):712-723.  View on PubMed
  7. 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 12 23; 142(51):21310-21321.  View on PubMed
  8. 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 11 25; 9.  View on PubMed
  9. 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. 2021 02; 1869(2):140562.  View on PubMed
  10. 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 10; 216(2):409-429.  View on PubMed
  11. 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.  View on PubMed
  12. 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 09 02; 142(35):14933-14939.  View on PubMed
  13. 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.  View on PubMed
  14. 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.  View on PubMed
  15. 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.  View on PubMed
  16. 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.  View on PubMed
  17. 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.  View on PubMed
  18. 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.  View on PubMed
  19. 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.  View on PubMed
  20. 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.  View on PubMed

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