Translational
Proteomics
Biomarkers can serve to track the evolution of physiological conditions in normal health and disease conditions, being powerful diagnostic and prognostic tools for precision medicine. The IRCM Biomarker Pipeline integrates a number of leading-edge technologies for monitoring changes in biomarkers, including their amino acid modifications (PTMs and mutations), their interactions with other cellular components, and their relative abundance. We collaborate with many groups both in Canada and abroad on various biomarkers related projects.
OVERVIEW OF THE PIPELINE

DISCOVERY
We privilege three technologies to identify proteins that change in response to disease conditions or as a result of disease-causative mutations:
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Protein affinity purification coupled with mass spectrometry (AP-MS with FLAG tag)
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Proximity-Dependent Protein Identification (BioID)
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Tandem Mass Tag Mass spectrometry (TMT-MS)
For examples, see:
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;294(18):7445-7459.
Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III
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.
Nat Commun. 2015 Jul 7;6:7623.
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.
VALIDATION
For the quantification of biomarkers in biological and clinical samples, we privilege a technology termed Protein Affinity Capture coupled with quantitative Mass Spectrometry (PAC-qMS). PAC-qMS can be operated at medium throughput (100s samples) and is ideal to quantify posttranslational modifications.
For examples, see:
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.
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.
Gauthier MS, Pérusse JR, Awan Z, Bouchard A, Tessier S, Champagne J, Krastins B, Byram G, Chabot K, Garneau P, Rabasa-Lhoret R, Faubert D, Lopez MF, Seidah NG, Coulombe B.
Methods. 2015 Jun 15;81:66-73.
ACTIVE PROJECTS
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Unraveling the molecular basis of novel forms of hypomyelinating leukodystrophies (CIHR, Lead G. Bernard MUHC).
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A biomarker discovery pipeline for precision medicine (Government of Quebec/IRCM, Lead B. Coulombe IRCM).
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A patient-derived iPSC platform of disease relevant cell models for biological studies (ALS Canada and Brain Canada, Lead G. Rouleau The Neuro).
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A machine learning approach to decipher protein-protein interactions in human plasma (IVADO and Genome Québec, Lead B. Coulombe IRCM).
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Modulation of protein interactions by the Superoxide Dismutase 1 (SOD1) (supported by Atomwise Inc, Lead B. Coulombe IRCM).
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The soluble fragment of neuroligin-1 as a blood biomarker of prodromal Alzheimer’s disease (Weston Brain Institute, Lead J. Brouillette HSCM).
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Characterization of neuro-muscular junctions in ALS patients (ALS Canada, Lead R. Robitaille, U Montreal).
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Reducing the activity of the phosphatase STEP to improve memory performance during aging (CIHR, Lead J. Brouillette HSCM).
Institut de recherches cliniques de Montréal (IRCM)
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