The Translational Proteomics research unit of Dr. Benoit Coulombe exploits the power of proteomics to understand how mutations that cause rare genetic diseases alter the function of their target proteins. In recent years, this team has mainly focused on hypomyelinating leukodystrophies, amyotrophic lateral sclerosis (ALS), some cardiometabolic conditions and rare cancers.
The identification of mutations causing rare diseases and the concomitant identification of the genes they target has become the norm in medical research, but these advances say little about the mechanism of disease onset and progression. Really useful clues, more difficult to obtain but also more informative, come from characterizing the defects caused by these mutations to the normal function of their target protein and downstream pathways. This information on disease mechanisms is a gold mine for biomarker and drug discovery, and the development of new treatments.
The Coulombe laboratory focuses more specifically on rare disease-causing gene products involved in protein-protein interactions. Indeed, it is estimated that an important proportion of rare diseases target protein-protein interactions, protein complexes and protein networks. The Coulombe laboratory being a pioneer in the study of the PAQosome, a molecular machine involved in the assembly and the maturation of protein complexes, this group is well positioned to characterize the organization and the biogenesis of the human interactome, and the faulty connections that cause diseases. Differential interactome data is presented at OpenForRare.com as part of an Open Science initiative.
- Director, Translational Proteomics Research Unit, IRCM
- Director, Biomarker Pipeline for Precision Medicine Strategic Initiative
- Full IRCM Research Professor
- Full Research Professor, Department of Biochemistry and Molecular Medicine (accreditation for the Molecular Biology Programs), Université de Montréal
- Holder of the Bell-Bombardier Chair of Excellence
Degrees and relevant experience
- PhD in molecular biology, Université de Montréal (1988)
- Postdoctoral fellowship, Banting and Best Department of Medical Research, University of Toronto (1990-1992)
- Postdoctoral fellowship, Free University of Brussels, Belgium (1992-1993)
- Assistant professor, Department of Biology, Université de Sherbrooke (1993-1996)
- Associate professor, Department of Biology, Université de Sherbrooke (1996-1999)
- Full professor, Department of Biology, Université de Sherbrooke (1999-2001)
- Full professor, Department of Biochemistry, Université de Montréal (since 2001)
Forget D, Lacombe AA, Cloutier P, Al-Khoury R, Bouchard A, Lavallée-Adam M, Faubert D, Jeronimo C, Blanchette M, Coulombe B. The protein interaction network of the human transcription machinery reveals a role for the conserved GTPase RPAP4/GPN1 and microtubule assembly in nuclear import and biogenesis of RNA polymerase II Mol Cell Proteomics. 2010 Dec;9(12):2827-39. doi: 10.1074/mcp.M110.003616. Epub 2010 Sep 20. PMID: 20855544
Seibold SA, Singh BN, Zhang C, Kireeva M, Domecq C, Bouchard A, Nazione AM, Feig M, Cukier RI, Coulombe B, Kashlev M, Hampsey M, Burton ZF. Conformational coupling, bridge helix dynamics and active site dehydration in catalysis by RNA polymerase Biochim Biophys Acta. 2010 Aug;1799(8):575-87. doi: 10.1016/j.bbagrm.2010.05.002. Epub 2010 May 15. PMID: 20478425
Cloutier P, Al-Khoury R, Lavallée-Adam M, Faubert D, Jiang H, Poitras C, Bouchard A, Forget D, Blanchette M, Coulombe B. High-resolution mapping of the protein interaction network for the human transcription machinery and affinity purification of RNA polymerase II-associated complexes Methods. 2009 Aug;48(4):381-6. doi: 10.1016/j.ymeth.2009.05.005. Epub 2009 May 18. PMID: 19450687
Krueger BJ, Jeronimo C, Roy BB, Bouchard A, Barrandon C, Byers SA, Searcey CE, Cooper JJ, Bensaude O, Cohen EA, Coulombe B, Price DH. LARP7 is a stable component of the 7SK snRNP while P-TEFb, HEXIM1 and hnRNP A1 are reversibly associated Nucleic Acids Res. 2008 Apr;36(7):2219-29. doi: 10.1093/nar/gkn061. Epub 2008 Feb 16. PMID: 18281698
Génome Québec - The projects of Benoit Coulombe and Éric Lécuyer received financial support under the IVADO Fundamental Research Funding Program.
- Ministère de l’Économie, des Sciences et de l’Innovation du Québec
- Leducq Foundation
- Canadian Institutes for Health Research (CIHR)
- Brain Canada
- ALS Canada
- Fondation Leucodystrophie
- Montreal Clinical Research Institute (IRCM)
- Génome Québec
Support biomedical research
Montreal Clinical Research Institute (IRCM)
110, des Pins Avenue West
Montréal, Québec H2W 1R7