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. 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.  View on PubMed
  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.  View on PubMed
  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.  View on PubMed
  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.  View on PubMed
  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.  View on PubMed
  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.  View on PubMed
  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.  View on PubMed
  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.  View on PubMed
  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.  View on PubMed
  10. Vasiljeva O, Menendez E, Nguyen M, Craik CS, Michael Kavanaugh W Monitoring protease activity in biological tissues using antibody prodrugs as sensing probes.  View on PubMed
  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.  View on PubMed
  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.  View on PubMed
  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.  View on PubMed
  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.  View on PubMed
  15. Ravalin M, Basu K, Gestwicki JE, Craik CS End-Binding E3 Ubiquitin Ligases Enable Protease Signaling.  View on PubMed
  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.  View on PubMed
  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.  View on PubMed
  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.  View on PubMed
  19. Basu K, Green EM, Cheng Y, Craik CS Why recombinant antibodies - benefits and applications.  View on PubMed
  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.  View on PubMed

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