Charles Craik

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Charles Craik

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Professor, School of Pharmacy
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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. Lund LR, Green KA, Stoop AA, Ploug M, Almholt K, Lilla J, Nielsen BS, Christensen IJ, Craik CS, Werb Z, Danø K, Rømer J. Plasminogen activation independent of uPA and tPA maintains wound healing in gene-deficient mice. EMBO J. 2006 Jun 21; 25(12):2686-97.
  2. Debela M, Magdolen V, Schechter N, Valachova M, Lottspeich F, Craik CS, Choe Y, Bode W, Goettig P. Specificity profiling of seven human tissue kallikreins reveals individual subsite preferences. J Biol Chem. 2006 Sep 01; 281(35):25678-88.
  3. Castro HC, Monteiro RQ, Assafim M, Loureiro NI, Craik C, Zingali RB. Ecotin modulates thrombin activity through exosite-2 interactions. Int J Biochem Cell Biol. 2006; 38(11):1893-900.
  4. Baird TT, Wright WD, Craik CS. Conversion of trypsin to a functional threonine protease. Protein Sci. 2006 Jun; 15(6):1229-38.
  5. Nomura AM, Marnett AB, Shimba N, Dötsch V, Craik CS. One functional switch mediates reversible and irreversible inactivation of a herpesvirus protease. Biochemistry. 2006 Mar 21; 45(11):3572-9.
  6. Choe Y, Leonetti F, Greenbaum DC, Lecaille F, Bogyo M, Brömme D, Ellman JA, Craik CS. Substrate profiling of cysteine proteases using a combinatorial peptide library identifies functionally unique specificities. J Biol Chem. 2006 May 05; 281(18):12824-32.
  7. Nomura AM, Marnett AB, Shimba N, Dötsch V, Craik CS. Induced structure of a helical switch as a mechanism to regulate enzymatic activity. Nat Struct Mol Biol. 2005 Nov; 12(11):1019-20.
  8. Herter S, Piper DE, Aaron W, Gabriele T, Cutler G, Cao P, Bhatt AS, Choe Y, Craik CS, Walker N, Meininger D, Hoey T, Austin RJ. Hepatocyte growth factor is a preferred in vitro substrate for human hepsin, a membrane-anchored serine protease implicated in prostate and ovarian cancers. Biochem J. 2005 Aug 15; 390(Pt 1):125-36.
  9. Bhatt AS, Erdjument-Bromage H, Tempst P, Craik CS, Moasser MM. Adhesion signaling by a novel mitotic substrate of src kinases. Oncogene. 2005 Aug 11; 24(34):5333-43.
  10. Mahrus S, Craik CS. Selective chemical functional probes of granzymes A and B reveal granzyme B is a major effector of natural killer cell-mediated lysis of target cells. Chem Biol. 2005 May; 12(5):567-77.
  11. Choe Y, Brinen LS, Price MS, Engel JC, Lange M, Grisostomi C, Weston SG, Pallai PV, Cheng H, Hardy LW, Hartsough DS, McMakin M, Tilton RF, Baldino CM, Craik CS. Development of alpha-keto-based inhibitors of cruzain, a cysteine protease implicated in Chagas disease. Bioorg Med Chem. 2005 Mar 15; 13(6):2141-56.
  12. Marnett AB, Craik CS. Papa's got a brand new tag: advances in identification of proteases and their substrates. Trends Biotechnol. 2005 Feb; 23(2):59-64.
  13. Matsumura M, Bhatt AS, Andress D, Clegg N, Takayama TK, Craik CS, Nelson PS. Substrates of the prostate-specific serine protease prostase/KLK4 defined by positional-scanning peptide libraries. Prostate. 2005 Jan 01; 62(1):1-13.
  14. Mahrus S, Kisiel W, Craik CS. Granzyme M is a regulatory protease that inactivates proteinase inhibitor 9, an endogenous inhibitor of granzyme B. J Biol Chem. 2004 Dec 24; 279(52):54275-82.
  15. Shimba N, Kovacs H, Stern AS, Nomura AM, Shimada I, Hoch JC, Craik CS, Dötsch V. Optimization of 13C direct detection NMR methods. J Biomol NMR. 2004 Oct; 30(2):175-9.
  16. Williamson AL, Lecchi P, Turk BE, Choe Y, Hotez PJ, McKerrow JH, Cantley LC, Sajid M, Craik CS, Loukas A. A multi-enzyme cascade of hemoglobin proteolysis in the intestine of blood-feeding hookworms. J Biol Chem. 2004 Aug 20; 279(34):35950-7.
  17. Serber Z, Straub W, Corsini L, Nomura AM, Shimba N, Craik CS, Ortiz de Montellano P, Dötsch V. Methyl groups as probes for proteins and complexes in in-cell NMR experiments. J Am Chem Soc. 2004 Jun 09; 126(22):7119-25.
  18. Ruggles SW, Fletterick RJ, Craik CS. Characterization of structural determinants of granzyme B reveals potent mediators of extended substrate specificity. J Biol Chem. 2004 Jul 16; 279(29):30751-9.
  19. Marnett AB, Nomura AM, Shimba N, Ortiz de Montellano PR, Craik CS. Communication between the active sites and dimer interface of a herpesvirus protease revealed by a transition-state inhibitor. Proc Natl Acad Sci U S A. 2004 May 04; 101(18):6870-5.
  20. Eggers CT, Murray IA, Delmar VA, Day AG, Craik CS. The periplasmic serine protease inhibitor ecotin protects bacteria against neutrophil elastase. Biochem J. 2004 Apr 01; 379(Pt 1):107-18.
  21. Na BK, Shenai BR, Sijwali PS, Choe Y, Pandey KC, Singh A, Craik CS, Rosenthal PJ. Identification and biochemical characterization of vivapains, cysteine proteases of the malaria parasite Plasmodium vivax. Biochem J. 2004 Mar 01; 378(Pt 2):529-38.
  22. Brachyurins. Tsu, C., and Craik, C.S. Handbook of Proteolytic Enzymes . 2004; 2nd Ed.
  23. Shimba, N. Nomura, A.M., Marnett, A.B. and Craik, C.S. Herpesvirus Protease Inhibition by Dimer Disruption. J. Virol. 2004; 12(78):6657-65 .
  24. Brachyurins. Tsu, C., and Craik, C.S. Handbook of Proteolytic Enzymes . 2004; 2nd Ed.
  25. Shimba, N. Nomura, A.M., Marnett, A.B. and Craik, C.S. Herpesvirus Protease Inhibition by Dimer Disruption. J. Virol. 2004; 12(78):6657-65 .