Translational Proteomics Laboratory, IRCM
Director: Benoit Coulombe PhD
Bell-Bombardier Research Chair, IRCM
Professor, Department of Biochemistry & Molecular Medicine, U of Montréal
Person in charge of Responsible Conduct of Research (RCR) at IRCM
Leader of the 37TrillionCells initiative
We are looking for exceptional people with expertise in proteomics, bioinformatics and/or single-cell technologies to join our lab. Please send a motivation letter and a complete CV by email directly to Benoit.Coulombe@ircm.qc.ca.
Information available soon
"We are developing cell-based interceptive medicine, which aims at identifying and treating disease at the first signs of molecular perturbations in the cell."
TOWARDS CELL-BASED INTERCEPTIVE MEDICINE
Combining proteome profiling, phage display and artificial intelligence to track the phenotypic trajectory of cells in disease
The cell is the fundamental unit of life. An interconnected and integrated amalgamation of 37.2 trillion cells with various functions make up the human body. Although the existence of the cell was revealed over 100 years ago, our knowledge of cells, their functions, molecular contents and interactions remains very limited. Only this knowledge, however, can provide an advanced understanding of how the human body works and the changes that lead to disease.
Our cells physically interact and communicate through a network of proteins located at their surface. These proteins regulate cell function and act like tags that together specify the identity of each cell. Moreover, in disease conditions, the activity and abundance of these receptor proteins is often altered, leading to modifications in cell-cell interactions and communications that result in aberrant gene expression programs and consequent cell dysfunction.
Our laboratory combines phage display and proteome profiling to decipher gene expression programs at single-cell resolution. We harness the power of phage display to discover fragment antibodies (FABs) that recognize antigens at the surface of disease cells in a specific manner. In collaboration with colleagues from the IRCM Cardiometabolic Health Research Centre, we are currently developing a FAB panel that will be used to apply Cytometry by Time of Flight (CyTOF) to quicky phenotype disease cells. To further define single-cell gene expression programs during the progression of disease, the FABs are also being used to isolate cell sub-populations that are then processed for single-cell proteomics (SCP) using a sensitive LC-MS/MS procedure.
The reliability of our LC-MS/MS procedure does not only allow to identify and classify cell sub-populations, but to go beyond this obviously descriptive analysis. Accurate quantification for thousands of single cells may provide sufficient data for deciphering both transcriptional and post-transcriptional regulation in single cells and for inferring direct causal mechanisms in biological systems and diseases. Proteins are the functional actors of the cell and multiple studies have shown that their level do not always correlate with cognate RNA level, making direct quantification of proteins a more reliable measurement of gene expression than RNA-seq.
Our research effort is located upstream of the development of a novel medical paradigm, “Cell-based Interceptive Medicine”, which is rapidly spreading in Europe (“LifeTime Initiative”; see Rajewski 2020 Nature) and which aims at treating diseases at the first sign of disruption of gene expression networks in cells that branch from health to disease. To accelerate the development of cell-based interceptive medicine in Québec/Canada, we have set up the 37TrillionCells initiative (www.37trillioncells.com) which brings together several laboratories using single-cell multiomic technologies.
Our PHAGE-Single Cell Proteomics-Artificial Intelligence (PHAGE-SCP-AI) pipeline, which is a central element of the 37TrillionCells initiative, promises to revolutionize the understanding, diagnosis and treatment of many diseases within 10 years. Diabetes, which affects more than 500 million people worldwide and can cause serious complications, is at the heart of our studies which extend to certain neurodegenerative diseases such as leukodystrophies.
As a member of 37TrillionCells, our lab is committed to openness, diversity and inclusion, trust, and national and international partnerships with academic and industrial groups, all conditions required to accelerate the discovery of medical treatments and the creation of wealth for the economy of Quebec/Canada.
RECENT PUBLICATIONS (2018-21)
Gaspar VP, Ramos AC, Philippe Cloutier, Pattaro Júnior JR, Duarte Junior FF, Bouchard A, Seixas FAV, Coulombe B, Fernandez MA
Curr. Issues Mol. Biol. 2021 Jul 22; 43(2), 767-781.
Sokullu E, Gauthier MS, Coulombe B
Viruses. 2021 Jun 10;13(6):1120.
Sudarshan D, Avvakumov N, Lalonde ME, Alerasool N, Jacquet K, Mameri A, Rousseau J, Lambert JP, Paquet E, Thonta Setty S, Loehr J, Gingras AC, Coulombe B, Taipale M, Doyon Y, Cote J
Biallelic pathogenic variants in LSM7impair assembly of LSM complexes, impairs neurodevelopment in zebrafish and may be associated with an ultra rare neurodevelopmental and neurodegenerative disorder
Derksen A, Shih HY, Forget D, Darbelli L, Tran LT, Poitras C, Guerrero K, Tharun S, Alkuraya FS, Kurdi WI, Nguyen CTE, Laberge AM, Si Y, Gauthier MS, Bonkowsky J*, Coulombe B*, Bernard G*. (*Co-senior authors)
HGG Adv. 2021. In Press.
Sokullu E, Pinard M, Gauthier MS, Coulombe B.
Expert Opin Drug Discov. 2021 Aug;16(8):881-895.
Pinard M, Cloutier P, Poitras C, Gauthier MS, Coulombe B.
Coulombe B, Derksen A, La Piana R, Brais B, Gauthier MS, Bernard G.
Fac Rev. 2021 Feb 5;10:12.
Djordjevic D, Pinard M, Gauthier MS, Smith-Hicks C, Hoffman TL, Wolf NI, Oegema R, van Binsbergen E, Baskin B, Bernard G, Fribourg S, Coulombe B, Yoon G.
Am J Hum Genet. 2021 Jan 7;108(1):186-193.
Cloutier P, Poitras C, Faubert D, Bouchard A, Blanchette M, Gauthier MS, Coulombe B.
J Proteome Res. 2020 Jan 3;19(1):18-27.
Ser-Phosphorylation of PCSK9 (Proprotein Convertase Subtilisin-Kexin 9) by Fam20C (Family With Sequence Similarity 20, Member C) Kinase Enhances Its Ability to Degrade the LDLR (Low-Density Lipoprotein Receptor)
Ben Djoudi Ouadda A, Gauthier MS, Susan-Resiga D, Girard E, Essalmani R, Black M, Marcinkiewicz J, Forget D, Hamelin J, Evagelidis A, Ly K, Day R, Galarneau L, Corbin F, Coulombe B, Çaku A, Tagliabracci VS, Seidah NG.
Arterioscler Thromb Vasc Biol. 2019 Oct;39(10):1996-2013.
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.
Mol Brain. 2019 Jun 20;12(1):59.
Choquet K, Forget D, Meloche E, Dicaire MJ, Bernard G, Vanderver A, Schiffmann R, Fabian MR, Teichmann M, Coulombe B, Brais B, Kleinman CL.
J Biol Chem. 2019 May 3;294(18):7445-7459.
Gauthier MS, Cloutier P, Coulombe B.
Adv Exp Med Biol. 2018;1106:25-36.
Coulombe B, Cloutier P, Gauthier MS.
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.
J Clin Lipidol. 2018 Jul-Aug;12(4):1027-1038.
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.
Am J Hum Genet. 2018 Apr 5;102(4):676-684.
Houry WA, Bertrand E, Coulombe B.
Trends Biochem Sci. 2018 Jan;43(1):4-9.
Honorary Lab Member
Diane Forget prend sa retraite après 27 ans de service dévoué pour le laboratoire. Elle a eu une contribution exceptionnelle pour nos publications, la formation de personnel, l'administration des fonds de recherche et la planification des espaces de laboratoire. Avec toute notre reconnaissance, merci et bonne continuation.
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