Our lab exploits the power of proteomics to advance the development of cures for various disorders, including some rare diseases and microbial infections
One of our main focus is to understand the mechanisms and regulation of RNA polymerases, the enzymes that make RNA copies of the information encoded in genomes (DNA). Transcription by RNA polymerases is the first, often the main site where gene expression is regulated. Human and bacterial RNA polymerases are privileged targets for drug discovery.
We have recently become extremely concerned by microbial infections, more particularly the emergence of novel viruses (SARS-CoV-2) and the bacterial resistance to antibiotics, which are both major threats to human health. We have initiated efforts aimed at targeting key microbial proteins, including RNA polymerases and coat proteins, to discover inhibitors of microbial infections.
Unraveling the molecular basis of novel forms of hypomyelinating leukodystrophies (CIHR, Lead G. Bernard MUHC).
A biomarker discovery pipeline for precision medicine (Government of Quebec/IRCM, Lead B. Coulombe IRCM).
A patient-derived iPSC platform of disease relevant cell models for biological studies (ALS Canada and Brain Canada, Lead G. Rouleau MNIH).
Deciphering breast cancer HER2-negativity with regard to HER2-targeted therapy (CIHR, Lead F. Durocher, U Laval).
A machine learning approach to decipher protein-protein interactions in human plasma (IVADO and Genome Québec, Lead B. Coulombe IRCM).
Modulation of protein interactions by the Superoxide Dismutase 1 (SOD1) (supported by Atomwise Inc, Lead B. Coulombe IRCM).
The soluble fragment of neuroligin-1 as a blood biomarker of prodromal Alzheimer’s disease (Weston Brain Institute, Lead J. Brouillette HSCM).
Characterization of neuro-muscular junctions in ALS patients (ALS Canada, Lead R. Robitaille, U Montreal).
Reducing the activity of the phosphatase STEP to improve memory performance during aging (CIHR, Lead J. Brouillette HSCM).
Screening of chemical compounds that correct assembly defects of RNA polymerase III carrying a leukodystrophy-causing mutation (Leukodystrophy’s Foundation, Lead B. Coulombe IRCM).
(Available as cost-shared collaborations)
Protein Affinity Purification coupled to Mass Spectrometry (AP-MS)
Proximity-Dependent Protein Identification (BioID)
Tandem Mass Tag (TMT)-Based Discovery Proteomics
Protein Affinity Capture coupled to quantitative Mass Spectrometry (PAC-qMS)
Phage Display Peptide/Protein Library Screening (PhD)
Chromatin Immunoprecipitation-PCR/Sequencing (ChIP-PCR/Seq)
Crosslinking coupled to Mass Spectrometry (XL-MS)
WHERE TO MEET US
February 29, 2020: Rare Disease Day, Ste-Justine CHU Research Centre, Montreal
April 4-7, 2020: ASBMB Annual Meeting, San Diego, USA (cancelled, abstracts published)
July 13-16, 2020: Splicing 2020, Caparica, Portugal
August 24-26, 2020: World Orphan Drug Congress USA 2020, National Harbor, Maryland, USA
PUBLICATIONS (past 3 years)
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.
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. 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). 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 C, Willis IM, Gauthier MS, Coulombe B, Brais B. The leukodystrophy mutation Polr3b R103H causes homozygote mouse embryonic lethality and impairs RNA polymerase III biogenesis. 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. Leukodystrophy-associated POLR3A mutations down-regulate the RNA polymerase III transcript and important regulatory RNA BC200. J Biol Chem. 2019 Mar 21. pii: jbc.RA118.006271.
Gauthier MS, Cloutier P, Coulombe B. Role of the PAQosome in Regulating Arrangement of Protein Quaternary Structure in Health and Disease. Adv Exp Med Biol. 2018;1106:25-36. doi: 10.1007/978-3-030-00737-9_3.
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.
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. Bi-allelic Mutations in EPRS, Encoding the Glutamyl-Prolyl-Aminoacyl-tRNA Synthetase, Cause a Hypomyelinating Leukodystrophy. Am J Hum Genet. 2018 Apr 5;102(4):676-684.
Lavallée-Adam M, Cloutier P, Coulombe B, Blanchette M. Functional 5' UTR motif discovery with LESMoN: Local Enrichment of Sequence Motifs in biological Networks. Nucleic Acids Res. 2017 Oct 13;45(18):10415-10427.
Cloutier P, Poitras C, Durand M, Fiola-Masson E, 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;8:15615.
Choquet K, Yang S, Moir RD, Forget D, Larivière R, Bouchard A, Poitras C, Sgarioto N, Dicaire MJ, Noohi F, Kennedy TE, Rochford J, Bernard G, Teichmann M, Coulombe B, Willis IM, Kleinman CL, Brais B. Absence of neurological abnormalities in mice homozygous for the Polr3a G672E hypomyelinating leukodystrophy mutation. Mol Brain. 2017 Apr 13;10(1):13.
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