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)
Djoudi Ouadda AB, Gauthier MS, Susan-Resiga D, Girard E, Essalmani R, Black M, Marcinkiewicz J, Hamelin J, Evagelidis A, Ly K, Day R, Galarneau L, Corbin F, Coulombe B, Çaku A, Tagliabracci V.S., Seidah N.G. Ser-Phosphorylation of PCSK9 (Proprotein Convertase Subtilisin-Kexin 9) by Fam20C Kinase Enhances Its Ability to Degrade the LDLR (Low-Density Lipoprotein Receptor) Arteriosclerosis, Thrombosis, and Vascular Biology, 2019 Oct;39(10):1996-2013. doi: 10.1161/ATVBAHA.119.313247. Epub 2019 Sep 5.
Choquet K, Pinard M, Yang S, Moir RD, Poitras C, Dicaire MJ, Sgarioto N, Larivière R, Kleinman CL, Willis IM, Gauthier MS, Coulombe B, Brais B. The leukodystrophy mutation Polr3b R103H causes homozygote mouse embryonic lethality and impairs RNA polymerase III biogenesis Mol Brain. 2019 Jun 20;12(1):59. doi: 10.1186/s13041-019-0479-7. PMID: 31221184
Choquet K, Forget D, Meloche E, Dicaire MJ, Bernard G, Vanderver A, Schiffmann R, Fabian MR, Teichmann M, Coulombe B, Brais B, Kleinman CL. Leukodystrophy-associated POLR3A mutations down-regulate the RNA polymerase III transcript and important regulatory RNA BC200 J Biol Chem. 2019 May 3;294(18):7445-7459. doi: 10.1074/jbc.RA118.006271. Epub 2019 Mar 21. PMID: 30898877
Gauthier MS, Awan Z, Bouchard A, Champagne J, Tessier S, Faubert D, Chabot K, Garneau PY, Rabasa-Lhoret R, Seidah NG, Ridker PM, Genest J, Coulombe B. Posttranslational modification of proprotein convertase subtilisin/kexin type 9 is differentially regulated in response to distinct cardiometabolic treatments as revealed by targeted proteomics J Clin Lipidol. 2018 Jul - Aug;12(4):1027-1038. doi: 10.1016/j.jacl.2018.03.092. Epub 2018 Apr 3. PMID: 29699916
Mendes MI, Gutierrez Salazar M, Guerrero K, Thiffault I, Salomons GS, Gauquelin L, Tran LT, Forget D, Gauthier MS, Waisfisz Q, Smith DEC, Simons C, van der Knaap MS, Marquardt I, Lemes A, Mierzewska H, Weschke B, Koehler W, Coulombe B, Wolf NI, Bernard G. Bi-allelic Mutations in EPRS, Encoding the Glutamyl-Prolyl-Aminoacyl-tRNA Synthetase, Cause a Hypomyelinating Leukodystrophy Am J Hum Genet. 2018 Apr 5;102(4):676-684. doi: 10.1016/j.ajhg.2018.02.011. Epub 2018 Mar 22. PMID: 29576217
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