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. Subramanian S, Hardt M, Choe Y, Niles RK, Johansen EB, Legac J, Gut J, Kerr ID, Craik CS, Rosenthal PJ. Hemoglobin cleavage site-specificity of the Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3. PLoS One. 2009; 4(4):e5156.
  2. Lilla JN, Joshi RV, Craik CS, Werb Z. Active plasma kallikrein localizes to mast cells and regulates epithelial cell apoptosis, adipocyte differentiation, and stromal remodeling during mammary gland involution. J Biol Chem. 2009 May 15; 284(20):13792-803.
  3. Schneider EL, Craik CS. Positional scanning synthetic combinatorial libraries for substrate profiling. Methods Mol Biol. 2009; 539:59-78.
  4. Raorane DA, Lim MD, Chen FF, Craik CS, Majumdar A. Quantitative and label-free technique for measuring protease activity and inhibition using a microfluidic cantilever array. Nano Lett. 2008 Sep; 8(9):2968-74.
  5. O'Brien TC, Mackey ZB, Fetter RD, Choe Y, O'Donoghue AJ, Zhou M, Craik CS, Caffrey CR, McKerrow JH. A parasite cysteine protease is key to host protein degradation and iron acquisition. J Biol Chem. 2008 Oct 24; 283(43):28934-43.
  6. O'Donoghue AJ, Mahon CS, Goetz DH, O'Malley JM, Gallagher DM, Zhou M, Murray PG, Craik CS, Tuohy MG. Inhibition of a secreted glutamic peptidase prevents growth of the fungus Talaromyces emersonii. J Biol Chem. 2008 Oct 24; 283(43):29186-95.
  7. Dolecková K, Kasný M, Mikes L, Cartwright J, Jedelský P, Schneider EL, Dvorák J, Mountford AP, Craik CS, Horák P. The functional expression and characterisation of a cysteine peptidase from the invasive stage of the neuropathogenic schistosome Trichobilharzia regenti. Int J Parasitol. 2009 Jan; 39(2):201-11.
  8. Lucas JJ, Hayes GR, Kalsi HK, Gilbert RO, Choe Y, Craik CS, Singh BN. Characterization of a cysteine protease from Tritrichomonas foetus that induces host-cell apoptosis. Arch Biochem Biophys. 2008 Sep 15; 477(2):239-43.
  9. Debela M, Beaufort N, Magdolen V, Schechter NM, Craik CS, Schmitt M, Bode W, Goettig P. Structures and specificity of the human kallikrein-related peptidases KLK 4, 5, 6, and 7. Biol Chem. 2008 Jun; 389(6):623-32.
  10. Farady CJ, Egea PF, Schneider EL, Darragh MR, Craik CS. Structure of an Fab-protease complex reveals a highly specific non-canonical mechanism of inhibition. J Mol Biol. 2008 Jul 04; 380(2):351-60.
  11. DuBois KN, Abodeely M, Sakanari J, Craik CS, Lee M, McKerrow JH, Sajid M. Identification of the major cysteine protease of Giardia and its role in encystation. J Biol Chem. 2008 Jun 27; 283(26):18024-31.
  12. Lim MD, Craik CS. Using specificity to strategically target proteases. Bioorg Med Chem. 2009 Feb 01; 17(3):1094-100.
  13. Darragh MR, Bhatt AS, Craik CS. MT-SP1 proteolysis and regulation of cell-microenvironment interactions. Front Biosci. 2008 Jan 01; 13:528-39.
  14. Stack CM, Caffrey CR, Donnelly SM, Seshaadri A, Lowther J, Tort JF, Collins PR, Robinson MW, Xu W, McKerrow JH, Craik CS, Geiger SR, Marion R, Brinen LS, Dalton JP. Structural and functional relationships in the virulence-associated cathepsin L proteases of the parasitic liver fluke, Fasciola hepatica. J Biol Chem. 2008 Apr 11; 283(15):9896-908.
  15. Lazic A, Goetz DH, Nomura AM, Marnett AB, Craik CS. Substrate modulation of enzyme activity in the herpesvirus protease family. J Mol Biol. 2007 Nov 02; 373(4):913-23.
  16. Hostetter DR, Loeb CR, Chu F, Craik CS. Hip is a pro-survival substrate of granzyme B. J Biol Chem. 2007 Sep 21; 282(38):27865-74.
  17. Goetz DH, Choe Y, Hansell E, Chen YT, McDowell M, Jonsson CB, Roush WR, McKerrow J, Craik CS. Substrate specificity profiling and identification of a new class of inhibitor for the major protease of the SARS coronavirus. Biochemistry. 2007 Jul 31; 46(30):8744-52.
  18. Liu GL, Rosa-Bauza YT, Salisbury CM, Craik C, Ellman JA, Chen FF, Lee LP. Peptide-nanoparticle hybrid SERS probes for optical detection of protease activity. J Nanosci Nanotechnol. 2007 Jul; 7(7):2323-30.
  19. Meléndez-López SG, Herdman S, Hirata K, Choi MH, Choe Y, Craik C, Caffrey CR, Hansell E, Chávez-Munguía B, Chen YT, Roush WR, McKerrow J, Eckmann L, Guo J, Stanley SL, Reed SL. Use of recombinant Entamoeba histolytica cysteine proteinase 1 to identify a potent inhibitor of amebic invasion in a human colonic model. Eukaryot Cell. 2007 Jul; 6(7):1130-6.
  20. Farady CJ, Sun J, Darragh MR, Miller SM, Craik CS. The mechanism of inhibition of antibody-based inhibitors of membrane-type serine protease 1 (MT-SP1). J Mol Biol. 2007 Jun 15; 369(4):1041-51.
  21. Bhatt AS, Welm A, Farady CJ, Vásquez M, Wilson K, Craik CS. Coordinate expression and functional profiling identify an extracellular proteolytic signaling pathway. Proc Natl Acad Sci U S A. 2007 Apr 03; 104(14):5771-6.
  22. Sojka D, Hajdusek O, Dvorák J, Sajid M, Franta Z, Schneider EL, Craik CS, Vancová M, Buresová V, Bogyo M, Sexton KB, McKerrow JH, Caffrey CR, Kopácek P. IrAE: an asparaginyl endopeptidase (legumain) in the gut of the hard tick Ixodes ricinus. Int J Parasitol. 2007 Jun; 37(7):713-24.
  23. Chu F, Mahrus S, Craik CS, Burlingame AL. Isotope-coded and affinity-tagged cross-linking (ICATXL): an efficient strategy to probe protein interaction surfaces. J Am Chem Soc. 2006 Aug 16; 128(32):10362-3.
  24. Park K, Kuechle MK, Choe Y, Craik CS, Lawrence OT, Presland RB. Expression and characterization of constitutively active human caspase-14. Biochem Biophys Res Commun. 2006 Sep 08; 347(4):941-8.
  25. Loeb CR, Harris JL, Craik CS. Granzyme B proteolyzes receptors important to proliferation and survival, tipping the balance toward apoptosis. J Biol Chem. 2006 Sep 22; 281(38):28326-35.