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. Kang D, Craik CS Identifying protease-activated targets and exploring therapeutic applications.  View on PubMed
  2. 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.  View on PubMed
  3. 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.  View on PubMed
  4. Detomasi TC, Degotte G, Huang S, Suryawanshi RK, Diallo A, Lizzadro L, Zaptero-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 Apr 25; 11(17):eadt7836.  View on PubMed
  5. 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.  View on PubMed
  6. 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 Mar 28; 387(6741):eadq8331.  View on PubMed
  7. 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 Jan 23; 108220.  View on PubMed
  8. 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
  9. 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
  10. 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 Sep 12; 15(1):7972.  View on PubMed
  11. 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
  12. Pandey A, Chopra S, Cleary SJ, López-Álvarez M, Quimby FM, Alanizi AAA, Sakhamuri S, Zhang N, Looney MR, Craik CS, Wilson DM, Evans MJ. Imaging the Granzyme Mediated Host Immune Response to Viral and Bacterial Pathogens In Vivo Using Positron Emission Tomography. ACS Infect Dis. 2024 Jun 14; 10(6):2108-2117.  View on PubMed
  13. Pourmal S, Green E, Bajaj R, Chemmama IE, Knudsen GM, Gupta M, Sali A, Cheng Y, Craik CS, Kroetz DL, Stroud RM. Structural basis of prostaglandin efflux by MRP4. Nat Struct Mol Biol. 2024 Apr; 31(4):621-632.  View on PubMed
  14. Shoichet BK, Craik CS. Preparing for the next pandemic. Science. 2023 11 10; 382(6671):649-650.  View on PubMed
  15. Detomasi TC, Batka AE, Valastyan JS, Hydorn MA, Craik CS, Bassler BL, Marletta MA. Proteases influence colony aggregation behavior in Vibrio cholerae. J Biol Chem. 2023 Dec; 299(12):105386.  View on PubMed
  16. Chung DH, Kong S, Young NJ, Chuo SW, Shiah JV, Connelly EJ, Rohweder PJ, Born A, Manglik A, Grandis JR, Johnson DE, Craik CS. Rare antibody phage isolation and discrimination (RAPID) biopanning enables identification of high-affinity antibodies against challenging targets. Commun Biol. 2023 10 12; 6(1):1036.  View on PubMed
  17. Sheik DA, Byers K, Thomas M, Rajesh UC, Ifuku K, Kirkwood K, Al-Haddad M, Craik CS, Davisson VJ. Addressing the unmet clinical need for low-volume assays in early diagnosis of pancreatic cancer. Front Gastroenterol (Lausanne). 2023; 2.  View on PubMed
  18. Nadel CM, Wucherer K, Oehler A, Thwin AC, Basu K, Callahan MD, Southworth DR, Mordes DA, Craik CS, Gestwicki JE. Phosphorylation of a Cleaved Tau Proteoform at a Single Residue Inhibits Binding to the E3 Ubiquitin Ligase, CHIP. bioRxiv. 2023 Aug 16.  View on PubMed
  19. Fink EA, Bardine C, Gahbauer S, Singh I, Detomasi TC, White K, Gu S, Wan X, Chen J, Ary B, Glenn I, O'Connell J, O'Donnell H, Fajtová P, Lyu J, Vigneron S, Young NJ, Kondratov IS, Alisoltani A, Simons LM, Lorenzo-Redondo R, Ozer EA, Hultquist JF, O'Donoghue AJ, Moroz YS, Taunton J, Renslo AR, Irwin JJ, García-Sastre A, Shoichet BK, Craik CS. Large library docking for novel SARS-CoV-2 main protease non-covalent and covalent inhibitors. Protein Sci. 2023 08; 32(8):e4712.  View on PubMed
  20. Suresh V, Sheik DA, Detomasi TC, Zhao T, Zepeda T, Saladi S, Rajesh UC, Byers K, Craik CS, Davisson VJ. A Prototype Assay Multiplexing SARS-CoV-2 3CL-Protease and Angiotensin-Converting Enzyme 2 for Saliva-Based Diagnostics in COVID-19. Biosensors (Basel). 2023 Jun 27; 13(7).  View on PubMed

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