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. 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
  2. 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
  3. 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
  4. Sampognaro PJ, Arya S, Knudsen GM, Gunderson EL, Sandoval-Perez A, Hodul M, Bowles K, Craik CS, Jacobson MP, Kao AW. Correction: Mutations in α-synuclein, TDP-43 and tau prolong protein half-life through diminished degradation by lysosomal proteases. Mol Neurodegener. 2023 May 30; 18(1):34.  View on PubMed
  5. Guzman KM, Cogan DP, Brodsky KL, Soohoo AM, Li X, Sevillano N, Mathews II, Nguyen KP, Craik CS, Khosla C. Discovery and Characterization of Antibody Probes of Module 2 of the 6-Deoxyerythronolide B Synthase. Biochemistry. 2023 06 06; 62(11):1589-1593.  View on PubMed
  6. Rashmi P, Sigdel TK, Rychkov D, Damm I, Da Silva AA, Vincenti F, Lourenco AL, Craik CS, Reiser J, Sarwal MM. Perturbations in podocyte transcriptome and biological pathways induced by FSGS associated circulating factors. Ann Transl Med. 2023 Jun 30; 11(9):315.  View on PubMed
  7. Sampognaro PJ, Arya S, Knudsen GM, Gunderson EL, Sandoval-Perez A, Hodul M, Bowles K, Craik CS, Jacobson MP, Kao AW. Mutations in α-synuclein, TDP-43 and tau prolong protein half-life through diminished degradation by lysosomal proteases. Mol Neurodegener. 2023 05 02; 18(1):29.  View on PubMed
  8. Nadel CM, Thwin AC, Callahan M, Lee K, Connelly E, Craik CS, Southworth DR, Gestwicki JE. The E3 Ubiquitin Ligase, CHIP/STUB1, Inhibits Aggregation of Phosphorylated Proteoforms of Microtubule-associated Protein Tau (MAPT). J Mol Biol. 2023 Mar 09; 168026.  View on PubMed
  9. Lourenço AL, Chuo SW, Bohn MF, Hann B, Khan S, Yevalekar N, Patel N, Yang T, Xu L, Lv D, Drakas R, Lively S, Craik CS. High-throughput optofluidic screening of single B cells identifies novel cross-reactive antibodies as inhibitors of uPAR with antibody-dependent effector functions. MAbs. 2023 Jan-Dec; 15(1):2184197.  View on PubMed
  10. Rohweder PJ, Jiang Z, Hurysz BM, O'Donoghue AJ, Craik CS. Multiplex substrate profiling by mass spectrometry for proteases. Methods Enzymol. 2023; 682:375-411.  View on PubMed
  11. Caiazza F, Conroy PC, Ivry SL, York T, Lin J, Hernandez S, Hoffmann TJ, Francis SS, Park WG, Yip-Schneider MT, Schmidt CM, Brand R, Craik CS, Kirkwood K. Accurate Identification of Mucinous Pancreatic Cystic Lesions Using Small-Volume Analytes. J Surg Res. 2023 04; 284:322-331.  View on PubMed
  12. 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 Coronavirus Disease 2019 Within a Healthcare Worker Cohort During the First Year of the Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic. Clin Infect Dis. 2022 Oct 29; 75(9):1573-1584.  View on PubMed
  13. Zhang Z, Rohweder PJ, Ongpipattanakul C, Basu K, Bohn MF, Dugan EJ, Steri V, Hann B, Shokat KM, Craik CS. A covalent inhibitor of K-Ras(G12C) induces MHC class I presentation of haptenated peptide neoepitopes targetable by immunotherapy. Cancer Cell. 2022 09 12; 40(9):1060-1069.e7.  View on PubMed
  14. Peters CE, Schulze-Gahmen U, Eckhardt M, Jang GM, Xu J, Pulido EH, Bardine C, Craik CS, Ott M, Gozani O, Verba KA, Hüttenhain R, Carette JE, Krogan NJ. Structure-function analysis of enterovirus protease 2A in complex with its essential host factor SETD3. Nat Commun. 2022 09 08; 13(1):5282.  View on PubMed
  15. 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. J Chem Inf Model. 2022 12 26; 62(24):6553-6573.  View on PubMed
  16. 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
  17. 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 05 19; 29(5):785-798.e19.  View on PubMed
  18. 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
  19. 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
  20. 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

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