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Cardiovascular and Metabolic Diseases

Translational Proteomics

Under the direction of Benoit Coulombe

Research Unit

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.

Benoit Coulombe

Research Unit Director

Phone:
514 987-5662
  • 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)

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Benoit Coulombe
Research Unit Director
Phone:
514 987-5662
Marie-Soleil Gauthier
Research Associate
Maxime Pinard
Research Associate
Esen Sokullu
Postdoctoral Fellow
Christian Poitras
Analyst
Phone:
514 987-5500, ext. 3379
Alexa Derksen
M. Sc. Student (supervisor: Dr. Geneviève Bernard)
Vijaya Madhoo
Administrative Assistant
Phone:
514 987-5632

Major Discoveries

  • In 2007, the Coulombe lab discovered a set of previously uncharacterized proteins that turned out to play a central role in biogenesis of protein complexes and networks in human cells. Among these regulatory proteins, the PAQosome is a multisubunit cochaperone composed of an R2TP core, a PFDL module and the two associated proteins WDR92 and POLR2E/RPB5. Its R2TP core is composed of PIH1D1 and RPAP3 (in light blue) that can be replaced by homologous proteins to form alternative PAQosomes and the hexameric RUVBL1/2 module. The PFDL module contains the canonical prefoldins PFDN2 and 6 and the prefoldin-like proteins URI1, UXT, and PDRG1. Client protein complexes to be assembled by the PAQosome together with chaperones (i.e. HSP70, HSP90 and CCT) can be recruited to the PAQosome directly or indirectly via adaptors.

Publications

Forget D, Lacombe AA, Cloutier P, Lavallée-Adam M, Blanchette M, Coulombe B. Nuclear import of RNA polymerase II is coupled with nucleocytoplasmic shuttling of the RNA polymerase II-associated protein 2 Nucleic Acids Res. 2013 Aug;41(14):6881-91. doi: 10.1093/nar/gkt455. Epub 2013 May 30. PMID: 23723243

 

Cloutier P, Coulombe B. Regulation of molecular chaperones through post-translational modifications: decrypting the chaperone code Biochim Biophys Acta. 2013 May;1829(5):443-54. doi: 10.1016/j.bbagrm.2013.02.010. Epub 2013 Feb 28. Review. PMID: 23459247

 

Krastins B, Prakash A, Sarracino DA, Nedelkov D, Niederkofler EE, Kiernan UA, Nelson R, Vogelsang MS, Vadali G, Garces A, Sutton JN, Peterman S, Byram G, Darbouret B, Pérusse JR, Seidah NG, Coulombe B, Gobom J, Portelius E, Pannee J, Blennow K, Kulasingam V, Couchman L, Moniz C, Lopez MF. Rapid development of sensitive, high-throughput, quantitative and highly selective mass spectrometric targeted immunoassays for clinically important proteins in human plasma and serum Clin Biochem. 2013 Apr;46(6):399-410. doi: 10.1016/j.clinbiochem.2012.12.019. Epub 2013 Jan 8. PMID: 23313081

Cloutier P, Lavallée-Adam M, Faubert D, Blanchette M, Coulombe B. A newly uncovered group of distantly related lysine methyltransferases preferentially interact with molecular chaperones to regulate their activity PLoS Genet. 2013;9(1):e1003210. doi: 10.1371/journal.pgen.1003210. Epub 2013 Jan 17. PMID: 23349634

 

Lavallée-Adam M, Rousseau J, Domecq C, Bouchard A, Forget D, Faubert D, Blanchette M, Coulombe B. Discovery of cell compartment specific protein-protein interactions using affinity purification combined with tandem mass spectrometry J Proteome Res. 2013 Jan 4;12(1):272-81. doi: 10.1021/pr300778b. Epub 2012 Dec 4. PMID: 23157168

Kireeva ML, Opron K, Seibold SA, Domecq C, Cukier RI, Coulombe B, Kashlev M, Burton ZF. Molecular dynamics and mutational analysis of the catalytic and translocation cycle of RNA polymerase BMC Biophys. 2012 Jun 7;5:11. doi: 10.1186/2046-1682-5-11. PMID: 22676913

 

Kireeva ML, Domecq C, Coulombe B, Burton ZF, Kashlev M. Interaction of RNA polymerase II fork loop 2 with downstream non-template DNA regulates transcription elongation J Biol Chem. 2011 Sep 2;286(35):30898-910. doi: 10.1074/jbc.M111.260844. Epub 2011 Jul 5. PMID: 21730074

 

Palangat M, Grass JA, Langelier MF, Coulombe B, Landick R. The RPB2 flap loop of human RNA polymerase II is dispensable for transcription initiation and elongation Mol Cell Biol. 2011 Aug;31(16):3312-25. doi: 10.1128/MCB.05318-11. Epub 2011 Jun 13. PMID: 21670157

Cojocaru M, Bouchard A, Cloutier P, Cooper JJ, Varzavand K, Price DH, Coulombe B.Transcription factor IIS cooperates with the E3 ligase UBR5 to ubiquitinate the CDK9 subunit of the positive transcription elongation factor B J Biol Chem. 2011 Feb 18;286(7):5012-22. doi: 10.1074/jbc.M110.176628. Epub 2010 Dec 2. PMID: 21127351

Lavallée-Adam M, Cloutier P, Coulombe B, Blanchette M. Modeling contaminants in AP-MS/MS experiments J Proteome Res. 2011 Feb 4;10(2):886-95. doi: 10.1021/pr100795z. Epub 2010 Dec 31. PMID: 21117706
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  • 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)
  • IVADO
  • Génome Québec

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Cardiovascular and Metabolic Diseases