Benoit Coulombe, PhD
Director, Department of Translational Proteomics, IRCM
Bell-Bombardier Research Chair, IRCM
Professor, Department of Biochemistry & Molecular Medicine, U of Montréal
Our lab is harnessing the power of recombinant antibody- and mass spectrometry-based proteomics to map protein/gene expression programs at single-cell resolution in health and disease
We are part of the 37TrillionCells Initiative
Our goal is to integrate single-cell (sc) proteomics to sc transcriptomics and sc epigenomics to track, understand and target human cells at different stages of disease progression, and analyse their response to drug treatment. We seek to characterize modulations of gene expression programs that accompany deviations of cell trajectories from health to disease. Our focus is currently on leukodystrophies, COVID-19, Alzheimer’s, cardiometabolic conditions and cancer.
For the past decades, technical limitations have forced scientists to focus their analysis of the transcriptome on measurements made on cell populations that can mask significant differences between individual cells. With the development of single-cell RNA-seq, it is now possible to profile the transcriptome of individual cells with unprecedented depth and thereby uncover, transcriptome-wide, the heterogeneity that exists within these populations. As a consequence, the specific function of each individual cell can be revealed. Because proteins are more often directly involved in gene regulation, single-cell proteome profiling represents a main challenge that also faces technical limitations, as mass spectrometry is currently not sensitive enough to profile the proteome of individual cells. Alternative proteomic methods are needed to overcome this important challenge.
Our group adopts a resolutely innovative modus operandi, which contributes to shaking up our classic methods by creating a transdisciplinary and open ecosystem where totally distinct approaches collide to allow both the study of the atomic structure of proteins and their organization in complex networks, both the analysis of microscopic model systems and of patient cohorts, both the screening of small molecules and their development to create affordable drugs.
To join the Coulombe lab as a graduate student or a postdoctoral fellow, please send a motivation letter and a complete CV by email directly to Benoit.Coulombe@ircm.qc.ca. Only candidates of interest will be contacted.
10 MOST SIGNIFICANT DISCOVERIES FROM OUR LAB
Robert F, Douziech M, Forget D, Egly JM, Greenblatt J, Burton ZF, Coulombe B.
Wrapping of promoter DNA around the RNA polymerase II initiation complex induced by TFIIF.
Mol Cell. 1998 Sep;2(3):341-51.
Jeronimo C, Forget D, Bouchard A, Li Q, Chua G, Poitras C, Thérien C, Bergeron D, Bourassa S, Greenblatt J, Chabot B, Poirier GG, Hughes TR, Blanchette M, Price DH, Coulombe B.
Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme.
Mol Cell. 2007 Jul 20;27(2):262-74.
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.
Thiffault I, Wolf NI, Forget D, Guerrero K, Tran LT, Choquet K, Lavallée-Adam M, Poitras C, Brais B, Yoon G, Sztriha L, Webster RI, Timmann D, van de Warrenburg BP, Seeger J, Zimmermann A, Máté A, Goizet C, Fung E, van der Knaap MS, Fribourg S, Vanderver A, Simons C, Taft RJ, Yates JR 3rd, Coulombe B, Bernard G.
Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III.
Nat Commun. 2015 Jul 7;6:7623.
Cloutier P, Poitras C, Durand M, Hekmat O, Fiola-Masson É, Bouchard A, Faubert D, Chabot B, Coulombe B.
R2TP/Prefoldin-like component RUVBL1/RUVBL2 directly interacts with ZNHIT2 to regulate assembly of U5 small nuclear ribonucleoprotein.
Nat Commun. 2017 May 31;8:15615.
Houry WA, Bertrand E, Coulombe B.
The PAQosome, an R2TP-Based Chaperone for Quaternary Structure Formation.
Trends Biochem Sci. 2018 Jan;43(1):4-9.
Coulombe B, Cloutier P, Gauthier MS.
How do our cells build their protein interactome?
Nat Commun. 2018 Jul 27;9(1):2955.
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.
Cloutier P, Poitras C, Faubert D, Bouchard A, Blanchette M, Gauthier MS, Coulombe B.
Upstream ORF-Encoded ASDURF Is a Novel Prefoldin-like Subunit of the PAQosome.
J Proteome Res. 2020 Jan 3;19(1):18-27.
Djurdja Djordjevic, Maxime Pinard, Marie-Soleil Gauthier, Constance Smith-Hicks, Trevor L. Hoffman, Nicole I. Wolf, Renske Oegema, Ellen van Binsbergen, Berivan Baskin, Geneviève Bernard, Sébastien Fribourg, Benoit Coulombe, Grace Yoon.
De novo variants in POLR3B cause ataxia, spasticity, and demyelinating neuropathy.
The American Journal of Human Genetics. 2021 Jan 7; 186–193.
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