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. O'Donoghue AJ, Jin Y, Knudsen GM, Perera NC, Jenne DE, Murphy JE, Craik CS, Hermiston TW. Global substrate profiling of proteases in human neutrophil extracellular traps reveals consensus motif predominantly contributed by elastase. PLoS One. 2013; 8(9):e75141.
  2. Corvo I, O'Donoghue AJ, Pastro L, Pi-Denis N, Eroy-Reveles A, Roche L, McKerrow JH, Dalton JP, Craik CS, Caffrey CR, Tort JF. Dissecting the active site of the collagenolytic cathepsin L3 protease of the invasive stage of Fasciola hepatica. PLoS Negl Trop Dis. 2013; 7(7):e2269.
  3. Small JL, O'Donoghue AJ, Boritsch EC, Tsodikov OV, Knudsen GM, Vandal O, Craik CS, Ehrt S. Substrate specificity of MarP, a periplasmic protease required for resistance to acid and oxidative stress in Mycobacterium tuberculosis. J Biol Chem. 2013 May 03; 288(18):12489-99.
  4. Raman K, Trivedi NN, Raymond WW, Ganesan R, Kirchhofer D, Verghese GM, Craik CS, Schneider EL, Nimishakavi S, Caughey GH. Mutational tail loss is an evolutionary mechanism for liberating marapsins and other type I serine proteases from transmembrane anchors. J Biol Chem. 2013 Apr 12; 288(15):10588-98.
  5. LeBeau AM, Duriseti S, Murphy ST, Pepin F, Hann B, Gray JW, VanBrocklin HF, Craik CS. Targeting uPAR with antagonistic recombinant human antibodies in aggressive breast cancer. Cancer Res. 2013 Apr 01; 73(7):2070-81.
  6. LeBeau AM, Lee M, Murphy ST, Hann BC, Warren RS, Delos Santos R, Kurhanewicz J, Hanash SM, VanBrocklin HF, Craik CS. Imaging a functional tumorigenic biomarker in the transformed epithelium. Proc Natl Acad Sci U S A. 2013 Jan 02; 110(1):93-8.
  7. Lee GM, Balouch E, Goetz DH, Lazic A, McKerrow JH, Craik CS. Mapping inhibitor binding modes on an active cysteine protease via nuclear magnetic resonance spectroscopy. Biochemistry. 2012 Dec 18; 51(50):10087-98.
  8. O'Donoghue AJ, Eroy-Reveles AA, Knudsen GM, Ingram J, Zhou M, Statnekov JB, Greninger AL, Hostetter DR, Qu G, Maltby DA, Anderson MO, Derisi JL, McKerrow JH, Burlingame AL, Craik CS. Global identification of peptidase specificity by multiplex substrate profiling. Nat Methods. 2012 Nov; 9(11):1095-100.
  9. Nimishakavi S, Besprozvannaya M, Raymond WW, Craik CS, Gruenert DC, Caughey GH. Activity and inhibition of prostasin and matriptase on apical and basolateral surfaces of human airway epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2012 Jul; 303(2):L97-106.
  10. Sojka D, Franta Z, Frantová H, Bartosová P, Horn M, Váchová J, O'Donoghue AJ, Eroy-Reveles AA, Craik CS, Knudsen GM, Caffrey CR, McKerrow JH, Mares M, Kopácek P. Characterization of gut-associated cathepsin D hemoglobinase from tick Ixodes ricinus (IrCD1). J Biol Chem. 2012 Jun 15; 287(25):21152-63.
  11. Wu S, Avila-Sakar A, Kim J, Booth DS, Greenberg CH, Rossi A, Liao M, Li X, Alian A, Griner SL, Juge N, Yu Y, Mergel CM, Chaparro-Riggers J, Strop P, Tampé R, Edwards RH, Stroud RM, Craik CS, Cheng Y. Fabs enable single particle cryoEM studies of small proteins. Structure. 2012 Apr 04; 20(4):582-92.
  12. Ingram JR, Rafi SB, Eroy-Reveles AA, Ray M, Lambeth L, Hsieh I, Ruelas D, Lim KC, Sakanari J, Craik CS, Jacobson MP, McKerrow JH. Investigation of the proteolytic functions of an expanded cercarial elastase gene family in Schistosoma mansoni. PLoS Negl Trop Dis. 2012; 6(4):e1589.
  13. Norbury LJ, Hung A, Beckham S, Pike RN, Spithill TW, Craik CS, Choe Y, Fecondo JV, Smooker PM. Analysis of Fasciola cathepsin L5 by S2 subsite substitutions and determination of the P1-P4 specificity reveals an unusual preference. Biochimie. 2012 May; 94(5):1119-27.
  14. Craik CS, Shahian T. A screening strategy for trapping the inactive conformer of a dimeric enzyme with a small molecule inhibitor. Methods Mol Biol. 2012; 928:119-31.
  15. Jäger S, Cimermancic P, Gulbahce N, Johnson JR, McGovern KE, Clarke SC, Shales M, Mercenne G, Pache L, Li K, Hernandez H, Jang GM, Roth SL, Akiva E, Marlett J, Stephens M, D'Orso I, Fernandes J, Fahey M, Mahon C, O'Donoghue AJ, Todorovic A, Morris JH, Maltby DA, Alber T, Cagney G, Bushman FD, Young JA, Chanda SK, Sundquist WI, Kortemme T, Hernandez RD, Craik CS, Burlingame A, Sali A, Frankel AD, Krogan NJ. Global landscape of HIV-human protein complexes. Nature. 2011 Dec 21; 481(7381):365-70.
  16. Jäger S, Kim DY, Hultquist JF, Shindo K, LaRue RS, Kwon E, Li M, Anderson BD, Yen L, Stanley D, Mahon C, Kane J, Franks-Skiba K, Cimermancic P, Burlingame A, Sali A, Craik CS, Harris RS, Gross JD, Krogan NJ. Vif hijacks CBF-ß to degrade APOBEC3G and promote HIV-1 infection. Nature. 2011 Dec 21; 481(7381):371-5.
  17. Schneider EL, Lee MS, Baharuddin A, Goetz DH, Farady CJ, Ward M, Wang CI, Craik CS. A reverse binding motif that contributes to specific protease inhibition by antibodies. J Mol Biol. 2012 Jan 27; 415(4):699-715.
  18. Kim J, Stroud RM, Craik CS. Rapid identification of recombinant Fabs that bind to membrane proteins. Methods. 2011 Dec; 55(4):303-9.
  19. Ray M, Hostetter DR, Loeb CR, Simko J, Craik CS. Inhibition of Granzyme B by PI-9 protects prostate cancer cells from apoptosis. Prostate. 2012 Jun 01; 72(8):846-55.
  20. de Poot SA, Westgeest M, Hostetter DR, Van Damme P, Plasman K, Demeyer K, Broekhuizen R, Gevaert K, Craik CS, Bovenschen N. Human and mouse granzyme M display divergent and species-specific substrate specificities. Biochem J. 2011 Aug 01; 437(3):431-42.
  21. Zhou Y, Agudelo J, Lu K, Goetz DH, Hansell E, Chen YT, Roush WR, McKerrow J, Craik CS, Amberg SM, Simmons G. Inhibitors of SARS-CoV entry--identification using an internally-controlled dual envelope pseudovirion assay. Antiviral Res. 2011 Nov; 92(2):187-94.
  22. Franta Z, Sojka D, Frantova H, Dvorak J, Horn M, Srba J, Talacko P, Mares M, Schneider E, Craik CS, McKerrow JH, Caffrey CR, Kopacek P. IrCL1 - the haemoglobinolytic cathepsin L of the hard tick, Ixodes ricinus. Int J Parasitol. 2011 Oct; 41(12):1253-62.
  23. Fahey ME, Bennett MJ, Mahon C, Jäger S, Pache L, Kumar D, Shapiro A, Rao K, Chanda SK, Craik CS, Frankel AD, Krogan NJ. GPS-Prot: a web-based visualization platform for integrating host-pathogen interaction data. BMC Bioinformatics. 2011 Jul 22; 12:298.
  24. Lee GM, Shahian T, Baharuddin A, Gable JE, Craik CS. Enzyme inhibition by allosteric capture of an inactive conformation. J Mol Biol. 2011 Sep 02; 411(5):999-1016.
  25. Craik CS, Page MJ, Madison EL. Proteases as therapeutics. Biochem J. 2011 Apr 01; 435(1):1-16.