Jean-Bernard Denault, Ph. D.

Investigator Jean-Bernard Denault
Cancer : Biology, Prognosis, and Diagnosis Axis
Centre de recherche du CHUS

Associate professor
Department of Pharmacology
Faculty of Medicine and Health Sciences
Université de Sherbrooke

Contact Information
Phone | 819 346-1110 ext. 12789

E-Mail | Jean-Bernard.Denault@USherbrooke.ca

  

Research relevance

Mechanisms of caspase activation, regulation and activity

Cell death by apoptosis is used on a daily basis to prevent the apparition of cancer cells. This process involves the proteolytic activity of a family of peptidases named caspases. Apoptosis is also required during embryogenesis, for immune system education, during tissues remodeling, for immuno-surveillance and to remove infected and damaged cells. Inflammatory processes required for a healthy response towards infections also employ caspases for the production of cytokines that are important for the immune system. Because the consequences of a deregulation of caspase biology are enormous, the mechanisms leading to their activation and the ones that control caspases once they are activated must be finely tuned.

The investigator Jean-Bernard Denault’s laboratory is particularly interested in the roles of caspases during the inflammatory response to influenza A infection, and in the fight against cancer appearance. His projects take advantage of protein engineering, enzymological characterization of caspases, genetic manipulation of cells, animal models of infection, structural biology and other approaches to understand how caspases work, and how these findings can lead to the development of new therapeutic strategies.

 

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Representative Achievements

  • Research program currently supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) and  the Fonds de recherche du Québec- Nature et technologies (FRQ-NT)
  • Boucher, D., Blais, V., and Denault, J.-B. (2012). Caspase 7 uses an exposited to promote poly(ADP ribose) polymerase 1 proteolysis. Proc. Natl. Acad. Sci. U.S.A. 109:5669-5674
  • Oberst, A., Pop. C., Tremblay, A.G., Blais, V., Denault, J.-B., Salvesen, G.S. and Green, D.R. (2010) Inducible dimerization and inducible cleavage reveal a requirement for both processes in caspase-8 activation. J. Biol. Chem. 285:16632-16642
  • Scott, F.L., Fuchs, G.J., Boyd, S.E., Denault, J.-B., Hawkins, C.J., Dequiedt, F., and Salvesen, G.S. (2008). Caspase-8 cleaved histone deacetylase 7 and abolishes its transcription repressor function. J. Biol. Chem. 283:19499-19510
  • Denault, J.-B., Drag, M. et Salvesen, G.S.; Alves, J., Heidt, A., Deveraux, Q. et Harris, J.L. (2007) Small molecules not direct activator of caspases. Nat. Chem. Biol. 3:519
  • Denault, J.-B., Békés, M., Scott, F.L., Boatright, K.M., Bogyo, M. and Salvesen, G.S. (2006). Engineered Hybrid Dimers: Tracking the Activation Pathway of Caspase-7. Mol. Cell 23:523-533

             

Know-How & Opportunities for Collaboration

  • Enzymology, protein biochemistry, proteolytic enzymes
  • Protein biochemistry techiques, molecular biology, protein expression, purification and characterization of proteolytic enzymes

         

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