Charles Craik

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Charles Craik

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Professor, School of Pharmacy
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Biography

My research interests focus on defining the roles and the mechanisms of enzymes and other challenging proteins in complex biological processes and on developing technologies to facilitate these studies. The current research in the Craik lab focuses on the chemical biology of proteolytic and protein degradation enzymes, receptors and membrane transporters. A particular emphasis of our work is on identifying the roles and regulating the activity of key proteins associated with infectious diseases, neurodegeneration and cancer. I am also interested in developing novel methods to biophysically characterize challenging proteins as well as their complexes. These studies coupled with our global substrate profiling, antibody engineering and noninvasive imaging efforts are providing a better understanding of both the chemical make-up and the biological importance of these critical proteins to aid in the rapid detection, monitoring and control of infectious disease, neurological disorders and cancer. This in turn is leading to the development of strategies for regulating these activities as a means of therapeutic intervention. Further study of these proteins holds promise for better understanding, rapid detection and eventual control of infectious diseases, cancer and neurodegeneration.
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  1. Louren?o 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.
  2. 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 Apr; 284:322-331.
  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 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.
  4. 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.
  5. 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.
  6. 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 Dec 26; 62(24):6553-6573.
  7. 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).
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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).
  14. 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 11 23; 15(11):18374-18384.
  15. 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.
  16. 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.
  17. Oâ Donnell HR, Tummino TA, Bardine C, Craik CS, Shoichet BK. Colloidal aggregators in biochemical SARS-CoV-2 repurposing screens. bioRxiv. 2021 Aug 31.
  18. 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.
  19. 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.
  20. Ravalin M, Craik CS. Beginning at the End(s): A Latent End-Binding Network at the Host-Pathogen Interface. Biochemistry. 2021 Jun 01; 60(21):1627-1629.
  21. 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.
  22. 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.
  23. 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.
  24. 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.
  25. 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.