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

  • March 1, 2021 - February 28, 2026 - Precision targeting of T cell cytotoxicity with PET , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA258297
  • April 20, 2021 - March 31, 2025 - New radiotracer development to study immune cell mobilization of granzyme proteolytic activity , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI161027
  • September 1, 2020 - August 31, 2024 - Probing the Role of Chaperone-TPR Complexes in Tau Proteostasis , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: RF1AG068125
  • August 27, 2007 - August 31, 2022 - HARC Center: HIV Accessory and Regulatory Complexes , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P50GM082250

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. Suresh V, Byers K, Rajesh UC, Caiazza F, Zhu G, Craik CS, Kirkwood K, Davisson VJ, Sheik DA. Translation of a Protease Turnover Assay for Clinical Discrimination of Mucinous Pancreatic Cysts. Diagnostics (Basel). 2022 May 28; 12(6).  View on PubMed
  2. Hulce KR, Jaishankar P, Lee GM, Bohn MF, Connelly EJ, Wucherer K, Ongpipattanakul C, Volk RF, Chuo SW, Arkin MR, Renslo AR, Craik CS. Inhibiting a dynamic viral protease by targeting a non-catalytic cysteine. Cell Chem Biol. 2022 May 19; 29(5):785-798.e19.  View on PubMed
  3. Doernberg SB, Holubar M, Jain V, Weng Y, Lu D, Bollyky JB, Sample H, Huang B, Craik CS, Desai M, Rutherford GW, Maldonado Y, CHART Study Consortium. Incidence and prevalence of COVID-19 within a healthcare worker cohort during the first year of the SARS-CoV-2 pandemic. Clin Infect Dis. 2022 Mar 12.  View on PubMed
  4. Santos LH, Kronenberger T, Almeida RG, Silva EB, Rocha REO, Oliveira JC, Barreto LV, Skinner D, Fajtová P, Giardini MA, Woodworth B, Bardine C, Lourenço AL, Craik CS, Poso A, Podust LM, McKerrow JH, Siqueira-Neto JL, O'Donoghue AJ, da Silva Júnior EN, Ferreira RS. Structure-based identification of naphthoquinones and derivatives as novel inhibitors of main protease Mpro and papain-like protease PLpro of SARS-CoV-2. bioRxiv. 2022 Jan 05.  View on PubMed
  5. O'Donnell HR, Tummino TA, Bardine C, Craik CS, Shoichet BK. Colloidal Aggregators in Biochemical SARS-CoV-2 Repurposing Screens. J Med Chem. 2021 12 09; 64(23):17530-17539.  View on PubMed
  6. Lindan CP, Desai M, Boothroyd D, Judson T, Bollyky J, Sample H, Weng Y, Cheng Y, Dahlen A, Hedlin H, Grumbach K, Henne J, Garcia S, Gonzales R, Craik CS, Rutherford G, Maldonado Y. Design of a population-based longitudinal cohort study of SARS-CoV-2 incidence and prevalence among adults in the San Francisco Bay Area. Ann Epidemiol. 2022 03; 67:81-100.  View on PubMed
  7. Cogan DP, Zhang K, Li X, Li S, Pintilie GD, Roh SH, Craik CS, Chiu W, Khosla C. Mapping the catalytic conformations of an assembly-line polyketide synthase module. Science. 2021 Nov 05; 374(6568):729-734.  View on PubMed
  8. Mahoney M, Damalanka VC, Tartell MA, Chung DH, Lourenço AL, Pwee D, Mayer Bridwell AE, Hoffmann M, Voss J, Karmakar P, Azouz NP, Klingler AM, Rothlauf PW, Thompson CE, Lee M, Klampfer L, Stallings CL, Rothenberg ME, Pöhlmann S, Whelan SPJ, 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. Proc Natl Acad Sci U S A. 2021 10 26; 118(43).  View on PubMed
  9. Pedroso CCS, Mann VR, Zuberbühler K, Bohn MF, Yu J, Altoe V, Craik CS, Cohen BE. Immunotargeting of Nanocrystals by SpyCatcher Conjugation of Engineered Antibodies. ACS Nano. 2021 Oct 25.  View on PubMed
  10. Meyer B, Chiaravalli J, Gellenoncourt S, Brownridge P, Bryne DP, Daly LA, Grauslys A, Walter M, Agou F, Chakrabarti LA, Craik CS, Eyers CE, Eyers PA, Gambin Y, Jones AR, Sierecki E, Verdin E, Vignuzzi M, Emmott E. Characterising proteolysis during SARS-CoV-2 infection identifies viral cleavage sites and cellular targets with therapeutic potential. Nat Commun. 2021 09 21; 12(1):5553.  View on PubMed
  11. Zhao N, Bardine C, Lourenço AL, Wang YH, Huang Y, Cleary SJ, Wilson DM, Oh DY, Fong L, Looney MR, Evans MJ, Craik CS. In Vivo Measurement of Granzyme Proteolysis from Activated Immune Cells with PET. ACS Cent Sci. 2021 Oct 27; 7(10):1638-1649.  View on PubMed
  12. Oâ Donnell HR, Tummino TA, Bardine C, Craik CS, Shoichet BK. Colloidal aggregators in biochemical SARS-CoV-2 repurposing screens. bioRxiv. 2021 Aug 31.  View on PubMed
  13. 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 05 27; 64(10):6706-6719.  View on PubMed
  14. 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
  15. Ravalin M, Craik CS. Beginning at the End(s): A Latent End-Binding Network at the Host-Pathogen Interface. Biochemistry. 2021 06 01; 60(21):1627-1629.  View on PubMed
  16. 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
  17. 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 06 10; 184(12):3192-3204.e16.  View on PubMed
  18. 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
  19. 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
  20. 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

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