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Translational Proteomics Laboratory, IRCM

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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.

News From our Lab

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"We are developing cell-based interceptive medicine, which aims at identifying and treating disease at the first signs of molecular perturbations in the cell."

Benoit Coulombe

 

TOWARDS CELL-BASED INTERCEPTIVE MEDICINE

Combining proteome profiling and phage display 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 (PHAGE-SCP) 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 and cancers.

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.

Cell-based interceptive medicine

We are part of the 37TrillionCells Initiative

The 37TrillionCells Initiative.png

RECENT PUBLICATIONS (2018-21)

Interactome Analysis of KIN (Kin17) Shows New Functions of This Protein

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.

Discovery of antivirals using phage display

Sokullu E, Gauthier MS, Coulombe B

Viruses. 2021 Jun 10;13(6):1120.

Recurrent chromosomal translocations in sarcomas create a mega-complex that mislocalizes NuA4/TIP60 to Polycomb target loci

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

https://doi.org/10.1101/2021.03.26.436670

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.

POLR3-related leukodystrophy: How do mutations affecting RNA polymerase III subunits cause hypomyelination?

Coulombe B, Derksen A, La Piana R, Brais B, Gauthier MS, Bernard G.

Fac Rev. 2021 Feb 5;10:12.

De novo variants in POLR3B cause ataxia, spasticity, and demyelinating neuropathy

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.

Upstream ORF-Encoded ASDURF Is a Novel Prefoldin-like Subunit of the PAQosome

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.

The leukodystrophy mutation Polr3b R103H causes homozygote mouse embryonic lethality and impairs RNA polymerase III biogenesis

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.

Leukodystrophy-associated POLR3A mutations down-regulate the RNA polymerase III transcript and important regulatory RNA BC200

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.

Role of the PAQosome in Regulating Arrangement of Protein Quaternary Structure in Health and Disease

Gauthier MS, Cloutier P, Coulombe B.

Adv Exp Med Biol. 2018;1106:25-36.

How do our cells build their protein interactome?

Coulombe B, Cloutier P, Gauthier MS.

Nat Commun. 2018 Jul 27;9(1):2955.

Posttranslational modification of proprotein convertase subtilisin/kexin type 9 is differentially regulated in response to distinct cardiometabolic treatments as revealed by targeted proteomics

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.

Bi-allelic Mutations in EPRS, Encoding the Glutamyl-Prolyl-Aminoacyl-tRNA Synthetase, Cause a Hypomyelinating Leukodystrophy

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.

The PAQosome, an R2TP-Based Chaperone for Quaternary Structure Formation

Houry WA, Bertrand E, Coulombe B.

Trends Biochem Sci. 2018 Jan;43(1):4-9.

 
 

ÉQUIPE

Dr. Benoit Coulombe
Dr. Benoit Coulombe
Directeur
Dr. Marie-Soleil Gauthier
Dr. Marie-Soleil Gauthier
Senior Associate Researcher
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Dr. Maxime Pinard
Associate Researcher
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Dr. Esen Sokullu
Postdoctoral Fellow
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Asmae Moursli
PhD student
Christian Poitras
Christian Poitras
Systems Analyst
Golden Marble
Vijaya Madhoo
Administrative Assistant
Diane Forget
Diane Forget
Honorary Lab Member

2020-06-26 :

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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