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. Stoop AA, Craik CS. Engineering of a macromolecular scaffold to develop specific protease inhibitors. Nat Biotechnol. 2003 Sep; 21(9):1063-8.
  2. Shimba N, Serber Z, Ledwidge R, Miller SM, Craik CS, Dötsch V. Quantitative identification of the protonation state of histidines in vitro and in vivo. Biochemistry. 2003 Aug 05; 42(30):9227-34.
  3. Bell JK, Goetz DH, Mahrus S, Harris JL, Fletterick RJ, Craik CS. The oligomeric structure of human granzyme A is a determinant of its extended substrate specificity. Nat Struct Biol. 2003 Jul; 10(7):527-34.
  4. Raymond WW, Ruggles SW, Craik CS, Caughey GH. Albumin is a substrate of human chymase. Prediction by combinatorial peptide screening and development of a selective inhibitor based on the albumin cleavage site. J Biol Chem. 2003 Sep 05; 278(36):34517-24.
  5. Leiting B, Pryor KD, Wu JK, Marsilio F, Patel RA, Craik CS, Ellman JA, Cummings RT, Thornberry NA. Catalytic properties and inhibition of proline-specific dipeptidyl peptidases II, IV and VII. Biochem J. 2003 Apr 15; 371(Pt 2):525-32.
  6. Mackewicz CE, Craik CS, Levy JA. The CD8+ cell noncytotoxic anti-HIV response can be blocked by protease inhibitors. Proc Natl Acad Sci U S A. 2003 Mar 18; 100(6):3433-8.
  7. Shimba N, Stern AS, Craik CS, Hoch JC, Dötsch V. Elimination of 13Calpha splitting in protein NMR spectra by deconvolution with maximum entropy reconstruction. J Am Chem Soc. 2003 Mar 05; 125(9):2382-3.
  8. Sun J, Pons J, Craik CS. Potent and selective inhibition of membrane-type serine protease 1 by human single-chain antibodies. Biochemistry. 2003 Feb 04; 42(4):892-900.
  9. Bhatt AS, Takeuchi T, Ylstra B, Ginzinger D, Albertson D, Shuman MA, Craik CS. Quantitation of membrane type serine protease 1 (MT-SP1) in transformed and normal cells. Biol Chem. 2003 Feb; 384(2):257-66.
  10. Barrios AM, Craik CS. Scanning the prime-site substrate specificity of proteolytic enzymes: a novel assay based on ligand-enhanced lanthanide ion fluorescence. Bioorg Med Chem Lett. 2002 Dec 16; 12(24):3619-23.
  11. Singh A, Shenai BR, Choe Y, Gut J, Sijwali PS, Craik CS, Rosenthal PJ. Critical role of amino acid 23 in mediating activity and specificity of vinckepain-2, a papain-family cysteine protease of rodent malaria parasites. Biochem J. 2002 Nov 15; 368(Pt 1):273-81.
  12. Wang X, Choe Y, Craik CS, Ellman JA. Design and synthesis of novel inhibitors of gelatinase B. Bioorg Med Chem Lett. 2002 Aug 19; 12(16):2201-4.
  13. Lecaille F, Choe Y, Brandt W, Li Z, Craik CS, Brömme D. Selective inhibition of the collagenolytic activity of human cathepsin K by altering its S2 subsite specificity. Biochemistry. 2002 Jul 02; 41(26):8447-54.
  14. Salter JP, Choe Y, Albrecht H, Franklin C, Lim KC, Craik CS, McKerrow JH. Cercarial elastase is encoded by a functionally conserved gene family across multiple species of schistosomes. J Biol Chem. 2002 Jul 05; 277(27):24618-24.
  15. Mathieu MA, Bogyo M, Caffrey CR, Choe Y, Lee J, Chapman H, Sajid M, Craik CS, McKerrow JH. Substrate specificity of schistosome versus human legumain determined by P1-P3 peptide libraries. Mol Biochem Parasitol. 2002 Apr 30; 121(1):99-105.
  16. Laboissière MC, Young MM, Pinho RG, Todd S, Fletterick RJ, Kuntz I, Craik CS. Computer-assisted mutagenesis of ecotin to engineer its secondary binding site for urokinase inhibition. J Biol Chem. 2002 Jul 19; 277(29):26623-31.
  17. Reiling KK, Endres NF, Dauber DS, Craik CS, Stroud RM. Anisotropic dynamics of the JE-2147-HIV protease complex: drug resistance and thermodynamic binding mode examined in a 1.09 A structure. Biochemistry. 2002 Apr 09; 41(14):4582-94.
  18. Wang B, Brown KC, Lodder M, Craik CS, Hecht SM. Chemically mediated site-specific proteolysis. Alteration of protein-protein interaction. Biochemistry. 2002 Feb 26; 41(8):2805-13.
  19. Maly DJ, Leonetti F, Backes BJ, Dauber DS, Harris JL, Craik CS, Ellman JA. Expedient solid-phase synthesis of fluorogenic protease substrates using the 7-amino-4-carbamoylmethylcoumarin (ACC) fluorophore. J Org Chem. 2002 Feb 08; 67(3):910-5.
  20. Pray TR, Reiling KK, Demirjian BG, Craik CS. Conformational change coupling the dimerization and activation of KSHV protease. Biochemistry. 2002 Feb 05; 41(5):1474-82.
  21. Dauber DS, Ziermann R, Parkin N, Maly DJ, Mahrus S, Harris JL, Ellman JA, Petropoulos C, Craik CS. Altered substrate specificity of drug-resistant human immunodeficiency virus type 1 protease. J Virol. 2002 Feb; 76(3):1359-68.
  22. Person MD, Brown KC, Mahrus S, Craik CS, Burlingame AL. Novel inter-protein cross-link identified in the GGH-ecotin D137Y dimer. Protein Sci. 2001 Aug; 10(8):1549-62.
  23. Harris JL, Niles A, Burdick K, Maffitt M, Backes BJ, Ellman JA, Kuntz I, Haak-Frendscho M, Craik CS. Definition of the extended substrate specificity determinants for beta-tryptases I and II. J Biol Chem. 2001 Sep 14; 276(37):34941-7.
  24. Castro HC, Silva DM, Craik C, Zingali RB. Structural features of a snake venom thrombin-like enzyme: thrombin and trypsin on a single catalytic platform? Biochim Biophys Acta. 2001 Jun 11; 1547(2):183-95.
  25. Eggers CT, Wang SX, Fletterick RJ, Craik CS. The role of ecotin dimerization in protease inhibition. J Mol Biol. 2001 May 18; 308(5):975-91.