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. Brown CM, Ray M, Eroy-Reveles AA, Egea P, Tajon C, Craik CS. Peptide length and leaving-group sterics influence potency of peptide phosphonate protease inhibitors. Chem Biol. 2011 Jan 28; 18(1):48-57.
  2. Farady CJ, Craik CS. Mechanisms of macromolecular protease inhibitors. Chembiochem. 2010 Nov 22; 11(17):2341-6.
  3. Swenerton RK, Zhang S, Sajid M, Medzihradszky KF, Craik CS, Kelly BL, McKerrow JH. The oligopeptidase B of Leishmania regulates parasite enolase and immune evasion. J Biol Chem. 2011 Jan 07; 286(1):429-40.
  4. Na BK, Bae YA, Zo YG, Choe Y, Kim SH, Desai PV, Avery MA, Craik CS, Kim TS, Rosenthal PJ, Kong Y. Biochemical properties of a novel cysteine protease of Plasmodium vivax, vivapain-4. PLoS Negl Trop Dis. 2010 Oct 12; 4(10):e849.
  5. Raymond WW, Trivedi NN, Makarova A, Ray M, Craik CS, Caughey GH. How immune peptidases change specificity: cathepsin G gained tryptic function but lost efficiency during primate evolution. J Immunol. 2010 Nov 01; 185(9):5360-8.
  6. Cruz CE, Fogaça AC, Nakayasu ES, Angeli CB, Belmonte R, Almeida IC, Miranda A, Miranda MT, Tanaka AS, Braz GR, Craik CS, Schneider E, Caffrey CR, Daffre S. Characterization of proteinases from the midgut of Rhipicephalus (Boophilus) microplus involved in the generation of antimicrobial peptides. Parasit Vectors. 2010 Jul 27; 3:63.
  7. Barkan DT, Hostetter DR, Mahrus S, Pieper U, Wells JA, Craik CS, Sali A. Prediction of protease substrates using sequence and structure features. Bioinformatics. 2010 Jul 15; 26(14):1714-22.
  8. Duriseti S, Goetz DH, Hostetter DR, LeBeau AM, Wei Y, Craik CS. Antagonistic anti-urokinase plasminogen activator receptor (uPAR) antibodies significantly inhibit uPAR-mediated cellular signaling and migration. J Biol Chem. 2010 Aug 27; 285(35):26878-88.
  9. He C, Nora GP, Schneider EL, Kerr ID, Hansell E, Hirata K, Gonzalez D, Sajid M, Boyd SE, Hruz P, Cobo ER, Le C, Liu WT, Eckmann L, Dorrestein PC, Houpt ER, Brinen LS, Craik CS, Roush WR, McKerrow J, Reed SL. A novel Entamoeba histolytica cysteine proteinase, EhCP4, is key for invasive amebiasis and a therapeutic target. J Biol Chem. 2010 Jun 11; 285(24):18516-27.
  10. Stoop AA, Joshi RV, Eggers CT, Craik CS. Analysis of an engineered plasma kallikrein inhibitor and its effect on contact activation. Biol Chem. 2010 Apr; 391(4):425-33.
  11. LeBeau AM, Kostova M, Craik CS, Denmeade SR. Prostate-specific antigen: an overlooked candidate for the targeted treatment and selective imaging of prostate cancer. Biol Chem. 2010 Apr; 391(4):333-43.
  12. Ohol YM, Goetz DH, Chan K, Shiloh MU, Craik CS, Cox JS. Mycobacterium tuberculosis MycP1 protease plays a dual role in regulation of ESX-1 secretion and virulence. Cell Host Microbe. 2010 Mar 18; 7(3):210-20.
  13. Sun C, Su KH, Valentine J, Rosa-Bauza YT, Ellman JA, Elboudwarej O, Mukherjee B, Craik CS, Shuman MA, Chen FF, Zhang X. Time-resolved single-step protease activity quantification using nanoplasmonic resonator sensors. ACS Nano. 2010 Feb 23; 4(2):978-84.
  14. Darragh MR, Schneider EL, Lou J, Phojanakong PJ, Farady CJ, Marks JD, Hann BC, Craik CS. Tumor detection by imaging proteolytic activity. Cancer Res. 2010 Feb 15; 70(4):1505-12.
  15. Camerer E, Barker A, Duong DN, Ganesan R, Kataoka H, Cornelissen I, Darragh MR, Hussain A, Zheng YW, Srinivasan Y, Brown C, Xu SM, Regard JB, Lin CY, Craik CS, Kirchhofer D, Coughlin SR. Local protease signaling contributes to neural tube closure in the mouse embryo. Dev Cell. 2010 Jan 19; 18(1):25-38.
  16. Jun YW, Sheikholeslami S, Hostetter DR, Tajon C, Craik CS, Alivisatos AP. Continuous imaging of plasmon rulers in live cells reveals early-stage caspase-3 activation at the single-molecule level. Proc Natl Acad Sci U S A. 2009 Oct 20; 106(42):17735-40.
  17. Sathler PC, Craik CS, Takeuchi T, Zingali RB, Castro HC. Engineering ecotin for identifying proteins with a trypsin fold. Appl Biochem Biotechnol. 2010 Apr; 160(8):2355-65.
  18. Shahian T, Lee GM, Lazic A, Arnold LA, Velusamy P, Roels CM, Guy RK, Craik CS. Inhibition of a viral enzyme by a small-molecule dimer disruptor. Nat Chem Biol. 2009 Sep; 5(9):640-6.
  19. Kerr ID, Lee JH, Farady CJ, Marion R, Rickert M, Sajid M, Pandey KC, Caffrey CR, Legac J, Hansell E, McKerrow JH, Craik CS, Rosenthal PJ, Brinen LS. Vinyl sulfones as antiparasitic agents and a structural basis for drug design. J Biol Chem. 2009 Sep 18; 284(38):25697-703.
  20. McKerrow JH, Doyle PS, Engel JC, Podust LM, Robertson SA, Ferreira R, Saxton T, Arkin M, Kerr ID, Brinen LS, Craik CS. Two approaches to discovering and developing new drugs for Chagas disease. Mem Inst Oswaldo Cruz. 2009 Jul; 104 Suppl 1:263-9.
  21. Mahon CS, O'Donoghue AJ, Goetz DH, Murray PG, Craik CS, Tuohy MG. Characterization of a multimeric, eukaryotic prolyl aminopeptidase: an inducible and highly specific intracellular peptidase from the non-pathogenic fungus Talaromyces emersonii. Microbiology. 2009 Nov; 155(Pt 11):3673-82.
  22. Dvorák J, Mashiyama ST, Sajid M, Braschi S, Delcroix M, Schneider EL, McKerrow WH, Bahgat M, Hansell E, Babbitt PC, Craik CS, McKerrow JH, Caffrey CR. SmCL3, a gastrodermal cysteine protease of the human blood fluke Schistosoma mansoni. PLoS Negl Trop Dis. 2009 Jun 02; 3(6):e449.
  23. Farady CJ, Sellers BD, Jacobson MP, Craik CS. Improving the species cross-reactivity of an antibody using computational design. Bioorg Med Chem Lett. 2009 Jul 15; 19(14):3744-7.
  24. Liz MA, Fleming CE, Nunes AF, Almeida MR, Mar FM, Choe Y, Craik CS, Powers JC, Bogyo M, Sousa MM. Substrate specificity of transthyretin: identification of natural substrates in the nervous system. Biochem J. 2009 Apr 15; 419(2):467-74.
  25. Lee GM, Craik CS. Trapping moving targets with small molecules. Science. 2009 Apr 10; 324(5924):213-5.