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
  • July 1, 2002 - June 30, 2022 - Research Training in Chemistry and Chemical Biology , Principal Investigator . Sponsor: NIH, Sponsor Award ID: T32GM064337
  • August 1, 2015 - July 31, 2020 - Mapping the conformational cycle of transmembrane transporters , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P01GM111126
  • September 24, 2014 - August 31, 2019 - Antibody Research Technology Center , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P41CA196276
  • July 10, 2013 - March 31, 2019 - Allosteric Inhibition of a Family of Proteolytic Enzymes , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01GM104659
  • January 1, 2015 - December 31, 2017 - Non-invasive Differentiation of Benign Lesions from Aggressive Pancreatic Cancer , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21CA185689
  • April 1, 2014 - March 31, 2016 - Extracellular Proteolysis as a Molecular Stratification Tool for Cancer , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21CA186077
  • March 1, 1982 - May 31, 2015 - Bio-Organic Biomedical Mass Spectrometry Resource , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P41RR001614
  • July 17, 2009 - June 30, 2014 - A Technological Platform for the Identification of Serine Proteases in Cancer , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA128765
  • June 1, 1976 - September 14, 2012 - Resource for Biocomputing, Visualization, and Informatics , Co-Investigator . Sponsor: NIH/NCRR, Sponsor Award ID: P41RR001081
  • April 17, 2007 - March 31, 2012 - Targeting Allosteric Studies to Modulate Protein Interactions and Function , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI067423
  • July 1, 2002 - June 30, 2010 - SFSU/UCSF Comprehensive Cancer Partnership Program , Co-Investigator . Sponsor: NIH, Sponsor Award ID: U56CA096216
  • June 10, 1997 - June 30, 2010 - Proteases in Cancer Biology and Drug Development , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: P01CA072006
  • May 1, 1995 - May 31, 2010 - Targeting Cysteine Proteases: Antiparasitic Chemotherapy , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P01AI035707
  • September 1, 1997 - August 31, 2007 - Structure Biology and Targeted Drug Design for AIDS , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P01GM056531
  • September 1, 1987 - August 31, 1997 - STRUCTURAL BIOLOGY AND TARGETED DRUG DESIGN FOR AIDS , Principal Investigator . Sponsor: NIH, Sponsor Award ID: P01GM039552

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. Zimanyi MA, Hulce KR, Bohn MF, Norman J, Rohweder PJ, Detomasi TC, Cheng Y, Craik CS. Antibody reveals conformational latch regulating dimerization in β- and γ-herpesvirus proteases. Nat Commun. 2026 Jul 13. View on PubMed
  2. Kang D, Pandey A, Kumar G, Mehta AS, Detomasi TC, Anderson D, Bardine C, Asper G, Qi J, Nadig I, Cui Y, Quimby FM, Ling J, Seo Y, Cohen BE, Anwar M, Evans MJ, Craik CS. A Prodrug Strategy to Conditionally Trap Therapeutic Payloads for Improved Tumor Retention. ACS Cent Sci. 2026 May 27; 12(5):719-730. View on PubMed
  3. Anderson KJ, Lee MS, Sevillano N, Chen G, Hornsby MJ, Sidhu SS, Craik CS. Structural Basis of Serine Protease Inhibition by Antibodies from Biased Fab Phage-Display Libraries. bioRxiv. 2026 Mar 14. View on PubMed
  4. Zimanyi M, Dayao M, Asencor AI, Kondapavulur S, Asaki J, McCutcheon K, Dabaco C, Bodansky A, Craik CS, Pleasure SJ, DeRisi JL, Cheng Y, Wilson MR, Pluvinage JV. Structure-guided design of a targeted autoantibody degrader for neurologic disease. bioRxiv. 2026 Feb 03. View on PubMed
  5. Aidlen D, Vo WVT, Young NJ, Rosecrans J, Kurianowicz A, Chuo SW, Asper GPR, Anderson D, Posner JA, Muir DF, Freitas N, Ott M, Craik CS, Taha TY, Pinney MM. Coupling high-throughput protease enzymology with viral replication reveals biochemical constraints of viral fitness. bioRxiv. 2026 Jan 28. View on PubMed
  6. Lizzadro L, Li J, Taha TY, Degotte G, Detomasi TC, Zapatero-Belinchon FJ, Hantz ER, Huang S, Matsui Y, Henderson WR, McCann JT, Montano M, Rosecrans J, Torres Pomares DF, McGovern BL, Diaz-Tapia R, Benjamin J, Gordon ME, Suazo ID, Settineri NS, Diallo A, Krogan NJ, Shoichet BK, Verba KA, Albrecht R, García-Sastre A, White KM, Ott M, Craik CS, Renslo AR. Discovery of Coronavirus Main Protease Inhibitors with Enhanced Brain Exposure and Potent Oral Efficacy in SARS-CoV-2 and MERS Infection Models. J Med Chem. 2026 Jan 22; 69(2):1530-1551. View on PubMed
  7. Liu Y, Nadig I, Mehta AS, Chuo SW, Ho YH, Tyler J, Craik CS, Anwar M, Cohen BE. Precision Labeling of Native Antibodies with Lock Coupling. J Am Chem Soc. 2026 01 14; 148(1):2008-2015. View on PubMed
  8. Leet DE, Jin J, Craik CS, Kattah MG, Long MD, Mahadevan U. Post-vaccination SARS-CoV-2 neutralizing antibodies in pregnant women receiving biologics for inflammatory bowel disease. PLoS One. 2025; 20(12):e0321242. View on PubMed
  9. Zimanyi M, Hulce KR, Bohn MF, Norman J, Rohweder PJ, Cheng Y, Craik CS. Antibody Reveals Conformational Latch Controlling Herpesvirus Proteases. bioRxiv. 2025 Oct 17. View on PubMed
  10. Kang D, Craik CS. Identifying protease-activated targets and exploring therapeutic applications. Expert Opin Ther Targets. 2025 Oct; 29(10):687-701. View on PubMed
  11. Fraser BJ, Young NJ, Bender BJ, Gahbauer S, Ilyassov O, Wilson RP, Li Y, Seitova A, Lourenço AL, Chung DH, Bardine C, Bénard F, Shoichet BK, Craik CS, Arrowsmith CH. Large Library Docking and Biophysical Analysis of Small-Molecule TMPRSS2 Inhibitors. J Med Chem. 2025 Oct 09; 68(19):19893-19907. View on PubMed
  12. Unnikrishnan A, Chung DH, Connelly EJ, Chuo SW, Devi S, Thwin AC, Nadel CM, Tse E, Gestwicki JE, Craik CS, Southworth DR. Structures of Fab-stabilized CHIP reveal a conformational switch important in E3 ligase and chaperone functions. bioRxiv. 2025 May 15. View on PubMed
  13. Detomasi TC, Degotte G, Huang S, Suryawanshi RK, Diallo A, Lizzadro L, Zapatero-Belinchón FJ, Taha TY, Li J, Richards AL, Hantz ER, Alam Z, Montano M, McCavitt-Malvido M, Gumpena R, Partridge JR, Correy GJ, Matsui Y, Charvat AF, Glenn IS, Rosecrans J, Revalde JL, Anderson D, Hultquist JF, Arkin MR, Neitz RJ, Swaney DL, Krogan NJ, Shoichet BK, Verba KA, Ott M, Renslo AR, Craik CS. Structure-based discovery of highly bioavailable, covalent, broad-spectrum coronavirus MPro inhibitors with potent in vivo efficacy. Sci Adv. 2025 04 25; 11(17):eadt7836. View on PubMed
  14. Kryštufek R, Verner V, Šácha P, Hadzima M, Trajhan F, Starková J, Tloušt'ová E, Dvoráková A, Pecina A, Brynda J, Chalupský K, Hájek M, Boucher MJ, Majer P, Rezác J, Madhani HD, Craik CS, Konvalinka J. On-Resin Assembly of Macrocyclic Inhibitors of Cryptococcus neoformans May1: A Pathway to Potent Antifungal Agents. J Med Chem. 2025 May 08; 68(9):9623-9637. View on PubMed
  15. Jain A, Heremans I, Rademaker G, Detomasi TC, Rohweder P, Anderson D, Zhang J, Hernandez GA, Gupta S, von Linde T, Lange M, Spacci M, Luo J, Citron YR, Olzmann JA, Dawson DW, Craik CS, Bommer G, Perera RM, Zoncu R. Leucine aminopeptidase LyLAP enables lysosomal degradation of membrane proteins. Science. 2025 03 28; 387(6741):eadq8331. View on PubMed
  16. Chung DH, Connelly EJ, Unnikrishnan A, Chuo SW, Wucherer K, Nadel CM, Gestwicki JE, Southworth DR, Craik CS. Recombinant antibodies inhibit enzymatic activity of the E3 ubiquitin ligase CHIP via multiple mechanisms. J Biol Chem. 2025 03; 301(3):108220. View on PubMed
  17. Pandey A, Rohweder PJ, Chan LM, Ongpipattanakul C, Chung DH, Paolella B, Quimby FM, Nguyen N, Verba KA, Evans MJ, Craik CS. Therapeutic Targeting and Structural Characterization of a Sotorasib-Modified KRAS G12C-MHC I Complex Demonstrate the Antitumor Efficacy of Hapten-Based Strategies. Cancer Res. 2025 Jan 15; 85(2):329-341. View on PubMed
  18. Jain A, Heremans I, Rademaker G, Detomasi TC, Hernandez GA, Zhang J, Gupta S, von Linde T, Lange M, Spacci M, Rohweder P, Anderson D, Citron YR, Olzmann JA, Dawson DW, Craik CS, Bommer G, Perera RM, Zoncu R. Leucine Aminopeptidase LyLAP enables lysosomal degradation of membrane proteins. bioRxiv. 2024 Dec 14. View on PubMed
  19. Nadel CM, Pokhrel S, Wucherer K, Oehler A, Thwin AC, Basu K, Callahan MD, Southworth DR, Mordes DA, Craik CS, Gestwicki JE. Phosphorylation of tau at a single residue inhibits binding to the E3 ubiquitin ligase, CHIP. Nat Commun. 2024 09 12; 15(1):7972. View on PubMed
  20. Mahoney MW, Helander J, Kooner AS, Norman M, Damalanka VC, De Bona P, Kasperkiewicz P, Rut W, Poreba M, Kashipathy MM, Battaile KP, Lovell S, O'Donoghue AJ, Craik CS, Drag M, Janetka JW. Use of protease substrate specificity screening in the rational design of selective protease inhibitors with unnatural amino acids: Application to HGFA, matriptase, and hepsin. Protein Sci. 2024 Aug; 33(8):e5110. View on PubMed

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