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Charles Craik
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Professor, School of Pharmacy
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Email: charles.craik@ucsf.edu
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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.
CTSI Profile Bio
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- Leontovyc A, Ulrychová L, O'Donoghue AJ, Vondrášek J, Marešová L, Hubálek M, Fajtová P, Chanová M, Jiang Z, Craik CS, Caffrey CR, Mareš M, Dvorák J, Horn M. SmSP2: A serine protease secreted by the blood fluke pathogen Schistosoma mansoni with anti-hemostatic properties. PLoS Negl Trop Dis. 2018 04; 12(4):e0006446.
- Corvo I, Ferraro F, Merlino A, Zuberbühler K, O'Donoghue AJ, Pastro L, Pi-Denis N, Basika T, Roche L, McKerrow JH, Craik CS, Caffrey CR, Tort JF. Substrate Specificity of Cysteine Proteases Beyond the S2 Pocket: Mutagenesis and Molecular Dynamics Investigation of Fasciola hepatica Cathepsins L. Front Mol Biosci. 2018; 5:40.
- Binning JM, Smith AM, Hultquist JF, Craik CS, Caretta Cartozo N, Campbell MG, Burton L, La Greca F, McGregor MJ, Ta HM, Bartholomeeusen K, Peterlin BM, Krogan NJ, Sevillano N, Cheng Y, Gross JD. Fab-based inhibitors reveal ubiquitin independent functions for HIV Vif neutralization of APOBEC3 restriction factors. PLoS Pathog. 2018 01; 14(1):e1006830.
- Dang S, Feng S, Tien J, Peters CJ, Bulkley D, Lolicato M, Zhao J, Zuberbühler K, Ye W, Qi L, Chen T, Craik CS, Jan YN, Minor DL, Cheng Y, Jan LY. Cryo-EM structures of the TMEM16A calcium-activated chloride channel. Nature. 2017 12 21; 552(7685):426-429.
- Ivry SL, Meyer NO, Winter MB, Bohn MF, Knudsen GM, O'Donoghue AJ, Craik CS. Global substrate specificity profiling of post-translational modifying enzymes. Protein Sci. 2018 03; 27(3):584-594.
- Winter MB, La Greca F, Arastu-Kapur S, Caiazza F, Cimermancic P, Buchholz TJ, Anderl JL, Ravalin M, Bohn MF, Sali A, O'Donoghue AJ, Craik CS. Immunoproteasome functions explained by divergence in cleavage specificity and regulation. Elife. 2017 11 28; 6.
- Truillet C, Oh HLJ, Yeo SP, Lee CY, Huynh LT, Wei J, Parker MFL, Blakely C, Sevillano N, Wang YH, Shen YS, Olivas V, Jami KM, Moroz A, Jego B, Jaumain E, Fong L, Craik CS, Chang AJ, Bivona TG, Wang CI, Evans MJ. Imaging PD-L1 Expression with ImmunoPET. Bioconjug Chem. 2018 01 17; 29(1):96-103.
- Isaac RS, Sanulli S, Tibble R, Hornsby M, Ravalin M, Craik CS, Gross JD, Narlikar GJ. Biochemical Basis for Distinct Roles of the Heterochromatin Proteins Swi6 and Chp2. J Mol Biol. 2017 Nov 24; 429(23):3666-3677.
- Acker TM, Gable JE, Bohn MF, Jaishankar P, Thompson MC, Fraser JS, Renslo AR, Craik CS. Allosteric Inhibitors, Crystallography, and Comparative Analysis Reveal Network of Coordinated Movement across Human Herpesvirus Proteases. J Am Chem Soc. 2017 08 30; 139(34):11650-11653.
- Kara E, Manna D, Løset GÅ, Schneider EL, Craik CS, Kanse S. Analysis of the substrate specificity of Factor VII activating protease (FSAP) and design of specific and sensitive peptide substrates. Thromb Haemost. 2017 08 30; 117(9):1750-1760.
- Wilkinson DJ, Habgood A, Lamb HK, Thompson P, Hawkins AR, Désilets A, Leduc R, Steinmetzer T, Hammami M, Lee MS, Craik CS, Watson S, Lin H, Milner JM, Rowan AD. Matriptase Induction of Metalloproteinase-Dependent Aggrecanolysis In Vitro and In Vivo: Promotion of Osteoarthritic Cartilage Damage by Multiple Mechanisms. Arthritis Rheumatol. 2017 08; 69(8):1601-1611.
- Roncase EJ, Moon C, Chatterjee S, González-Páez GE, Craik CS, O'Donoghue AJ, Wolan DW. Substrate Profiling and High Resolution Co-complex Crystal Structure of a Secreted C11 Protease Conserved across Commensal Bacteria. ACS Chem Biol. 2017 06 16; 12(6):1556-1565.
- Ivry SL, Sharib JM, Dominguez DA, Roy N, Hatcher SE, Yip-Schneider MT, Schmidt CM, Brand RE, Park WG, Hebrok M, Kim GE, O'Donoghue AJ, Kirkwood KS, Craik CS. Global Protease Activity Profiling Provides Differential Diagnosis of Pancreatic Cysts. Clin Cancer Res. 2017 Aug 15; 23(16):4865-4874.
- Lourenço AL, Salvador RRS, Silva LA, Saito MS, Mello JFR, Cabral LM, Rodrigues CR, Vera MAF, Muri EMF, de Souza AMT, Craik CS, Dias LRS, Castro HC, Sathler PC. Synthesis and mechanistic evaluation of novel N'-benzylidene-carbohydrazide-1H-pyrazolo[3,4-b]pyridine derivatives as non-anionic antiplatelet agents. Eur J Med Chem. 2017 Jul 28; 135:213-229.
- Meyer NO, O'Donoghue AJ, Schulze-Gahmen U, Ravalin M, Moss SM, Winter MB, Knudsen GM, Craik CS. Multiplex Substrate Profiling by Mass Spectrometry for Kinases as a Method for Revealing Quantitative Substrate Motifs. Anal Chem. 2017 04 18; 89(8):4550-4558.
- Guo CJ, Chang FY, Wyche TP, Backus KM, Acker TM, Funabashi M, Taketani M, Donia MS, Nayfach S, Pollard KS, Craik CS, Cravatt BF, Clardy J, Voigt CA, Fischbach MA. Discovery of Reactive Microbiota-Derived Metabolites that Inhibit Host Proteases. Cell. 2017 01 26; 168(3):517-526.e18.
- Clarke SC, Dumesic PA, Homer CM, O'Donoghue AJ, La Greca F, Pallova L, Majer P, Madhani HD, Craik CS. Integrated Activity and Genetic Profiling of Secreted Peptidases in Cryptococcus neoformans Reveals an Aspartyl Peptidase Required for Low pH Survival and Virulence. PLoS Pathog. 2016 Dec; 12(12):e1006051.
- Barkan DT, Cheng XL, Celino H, Tran TT, Bhandari A, Craik CS, Sali A, Smythe ML. Clustering of disulfide-rich peptides provides scaffolds for hit discovery by phage display: application to interleukin-23. BMC Bioinformatics. 2016 Nov 23; 17(1):481.
- Winter MB, Salcedo EC, Lohse MB, Hartooni N, Gulati M, Sanchez H, Takagi J, Hube B, Andes DR, Johnson AD, Craik CS, Nobile CJ. Global Identification of Biofilm-Specific Proteolysis in Candida albicans. MBio. 2016 09 13; 7(5).
- O'Donoghue AJ, Ivry SL, Chaudhury C, Hostetter DR, Hanahan D, Craik CS. Procathepsin E is highly abundant but minimally active in pancreatic ductal adenocarcinoma tumors. Biol Chem. 2016 09 01; 397(9):871-81.
- Goupil LS, Ivry SL, Hsieh I, Suzuki BM, Craik CS, O'Donoghue AJ, McKerrow JH. Cysteine and Aspartyl Proteases Contribute to Protein Digestion in the Gut of Freshwater Planaria. PLoS Negl Trop Dis. 2016 08; 10(8):e0004893.
- Duan C, Alibakhshi MA, Kim DK, Brown CM, Craik CS, Majumdar A. Label-Free Electrical Detection of Enzymatic Reactions in Nanochannels. ACS Nano. 2016 08 23; 10(8):7476-84.
- Lentz CS, Ordonez AA, Kasperkiewicz P, La Greca F, O'Donoghue AJ, Schulze CJ, Powers JC, Craik CS, Drag M, Jain SK, Bogyo M. Design of Selective Substrates and Activity-Based Probes for Hydrolase Important for Pathogenesis 1 (HIP1) from Mycobacterium tuberculosis. ACS Infect Dis. 2016 11 11; 2(11):807-815.
- Homer CM, Summers DK, Goranov AI, Clarke SC, Wiesner DL, Diedrich JK, Moresco JJ, Toffaletti D, Upadhya R, Caradonna I, Petnic S, Pessino V, Cuomo CA, Lodge JK, Perfect J, Yates JR, Nielsen K, Craik CS, Madhani HD. Intracellular Action of a Secreted Peptide Required for Fungal Virulence. Cell Host Microbe. 2016 Jun 08; 19(6):849-64.
- Le Gall SM, Szabo R, Lee M, Kirchhofer D, Craik CS, Bugge TH, Camerer E. Matriptase activation connects tissue factor-dependent coagulation initiation to epithelial proteolysis and signaling. Blood. 2016 06 23; 127(25):3260-9.