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. Drake CR, Sevillano N, Truillet C, Craik CS, VanBrocklin HF, Evans MJ. Site-Specific Radiofluorination of Biomolecules with 8-[(18)F]-Fluorooctanoic Acid Catalyzed by Lipoic Acid Ligase. ACS Chem Biol. 2016 06 17; 11(6):1587-94.
  2. Julien O, Zhuang M, Wiita AP, O'Donoghue AJ, Knudsen GM, Craik CS, Wells JA. Quantitative MS-based enzymology of caspases reveals distinct protein substrate specificities, hierarchies, and cellular roles. Proc Natl Acad Sci U S A. 2016 Apr 05; 113(14):E2001-10.
  3. Li H, O'Donoghue AJ, van der Linden WA, Xie SC, Yoo E, Foe IT, Tilley L, Craik CS, da Fonseca PC, Bogyo M. Structure- and function-based design of Plasmodium-selective proteasome inhibitors. Nature. 2016 Feb 11; 530(7589):233-6.
  4. Gable JE, Lee GM, Acker TM, Hulce KR, Gonzalez ER, Schweigler P, Melkko S, Farady CJ, Craik CS. Fragment-Based Protein-Protein Interaction Antagonists of a Viral Dimeric Protease. ChemMedChem. 2016 Apr 19; 11(8):862-9.
  5. Bibo-Verdugo B, O'Donoghue AJ, Rojo-Arreola L, Craik CS, García-Carreño F. Complementary Proteomic and Biochemical Analysis of Peptidases in Lobster Gastric Juice Uncovers the Functional Role of Individual Enzymes in Food Digestion. Mar Biotechnol (NY). 2016 Apr; 18(2):201-14.
  6. Jones SK, Clarke SC, Craik CS, Bennett RJ. Evolutionary Selection on Barrier Activity: Bar1 Is an Aspartyl Protease with Novel Substrate Specificity. MBio. 2015 Nov 24; 6(6):e01604-15.
  7. Wong KR, Menendez E, Craik CS, Kavanaugh WM, Vasiljeva O. In vivo imaging of protease activity by Probody therapeutic activation. Biochimie. 2016 Mar; 122:62-7.
  8. Page MJ, Lourenço AL, David T, LeBeau AM, Cattaruzza F, Castro HC, VanBrocklin HF, Coughlin SR, Craik CS. Non-invasive imaging and cellular tracking of pulmonary emboli by near-infrared fluorescence and positron-emission tomography. Nat Commun. 2015 Oct 01; 6:8448.
  9. Dvorák J, Fajtová P, Ulrychová L, Leontovyc A, Rojo-Arreola L, Suzuki BM, Horn M, Mareš M, Craik CS, Caffrey CR, O'Donoghue AJ. Excretion/secretion products from Schistosoma mansoni adults, eggs and schistosomula have unique peptidase specificity profiles. Biochimie. 2016 Mar; 122:99-109.
  10. O'Donoghue AJ, Knudsen GM, Beekman C, Perry JA, Johnson AD, DeRisi JL, Craik CS, Bennett RJ. Destructin-1 is a collagen-degrading endopeptidase secreted by Pseudogymnoascus destructans, the causative agent of white-nose syndrome. Proc Natl Acad Sci U S A. 2015 Jun 16; 112(24):7478-83.
  11. Wermelinger LS, Frattani FS, Carneiro-Lobo TC, Craik CS, Castro HC, Zingali RB. Ecotin: Exploring a feasible antithrombotic profile. Int J Biol Macromol. 2015 Jul; 78:296-303.
  12. LeBeau AM, Sevillano N, Markham K, Winter MB, Murphy ST, Hostetter DR, West J, Lowman H, Craik CS, VanBrocklin HF. Imaging active urokinase plasminogen activator in prostate cancer. Cancer Res. 2015 Apr 01; 75(7):1225-35.
  13. Sharma V, Panwar P, O'Donoghue AJ, Cui H, Guido RV, Craik CS, Brömme D. Structural requirements for the collagenase and elastase activity of cathepsin K and its selective inhibition by an exosite inhibitor. Biochem J. 2015 Jan 01; 465(1):163-73.
  14. Kim J, Wu S, Tomasiak TM, Mergel C, Winter MB, Stiller SB, Robles-Colmanares Y, Stroud RM, Tampé R, Craik CS, Cheng Y. Subnanometre-resolution electron cryomicroscopy structure of a heterodimeric ABC exporter. Nature. 2015 Jan 15; 517(7534):396-400.
  15. Skala W, Utzschneider DT, Magdolen V, Debela M, Guo S, Craik CS, Brandstetter H, Goettig P. Structure-function analyses of human kallikrein-related peptidase 2 establish the 99-loop as master regulator of activity. J Biol Chem. 2014 Dec 05; 289(49):34267-83.
  16. Mahon C, Krogan NJ, Craik CS, Pick E. Cullin E3 ligases and their rewiring by viral factors. Biomolecules. 2014 Oct 13; 4(4):897-930.
  17. Gable JE, Acker TM, Craik CS. Current and potential treatments for ubiquitous but neglected herpesvirus infections. Chem Rev. 2014 Nov 26; 114(22):11382-412.
  18. Tajon CA, Seo D, Asmussen J, Shah N, Jun YW, Craik CS. Sensitive and selective plasmon ruler nanosensors for monitoring the apoptotic drug response in leukemia. ACS Nano. 2014 Sep 23; 8(9):9199-208.
  19. Lucas JM, Heinlein C, Kim T, Hernandez SA, Malik MS, True LD, Morrissey C, Corey E, Montgomery B, Mostaghel E, Clegg N, Coleman I, Brown CM, Schneider EL, Craik C, Simon JA, Bedalov A, Nelson PS. The androgen-regulated protease TMPRSS2 activates a proteolytic cascade involving components of the tumor microenvironment and promotes prostate cancer metastasis. Cancer Discov. 2014 Nov; 4(11):1310-25.
  20. Gable JE, Lee GM, Jaishankar P, Hearn BR, Waddling CA, Renslo AR, Craik CS. Broad-spectrum allosteric inhibition of herpesvirus proteases. Biochemistry. 2014 Jul 22; 53(28):4648-60.
  21. Grove LM, Southern BD, Jin TH, White KE, Paruchuri S, Harel E, Wei Y, Rahaman SO, Gladson CL, Ding Q, Craik CS, Chapman HA, Olman MA. Urokinase-type plasminogen activator receptor (uPAR) ligation induces a raft-localized integrin signaling switch that mediates the hypermotile phenotype of fibrotic fibroblasts. J Biol Chem. 2014 May 02; 289(18):12791-804.
  22. LeBeau AM, Sevillano N, King ML, Duriseti S, Murphy ST, Craik CS, Murphy LL, VanBrocklin HF. Imaging the urokinase plasminongen activator receptor in preclinical breast cancer models of acquired drug resistance. Theranostics. 2014; 4(3):267-79.
  23. Tajon C, Jun YW, Craik CS. Single-molecule sensing of caspase activation in live cells via plasmon coupling nanotechnology. Methods Enzymol. 2014; 544:271-97.
  24. Asmussen J, Lasater EA, Tajon C, Oses-Prieto J, Jun YW, Taylor BS, Burlingame A, Craik CS, Shah NP. MEK-dependent negative feedback underlies BCR-ABL-mediated oncogene addiction. Cancer Discov. 2014 Feb; 4(2):200-15.
  25. Du X, Chen NL, Wong A, Craik CS, Brömme D. Elastin degradation by cathepsin V requires two exosites. J Biol Chem. 2013 Nov 29; 288(48):34871-81.