Dr. Jean-Yves Masson is a researcher at the CHU of Quebec-Laval University Research Centre, Oncology axis, and Full Professor in the Department of Molecular Biology, Medical Biochemistry and Pathology at Laval University’s School of Medicine. He joined the CHU of Quebec following a postdoctoral fellowship in the laboratory of Stephen West a world specialist in DNA double-strand break repair by homologous recombination. Since then, he has received numerous awards, including the prestigious title of FRQS National Researcher award, and has published over 125 articles in leading scientific journals, including Nature, Nature Communications, and Molecular Cell. He is holding a FRQS Research Chair until June 2020. In parallel with his research activities, Dr. Masson was acting as fundamental research representative on the planning and coordination committee of the Cancer Research Centre/Oncology Axis in 2011 and was member of the executive committee of the Oncology axis in 2012. He also served as Director of the Department of Molecular Biology, Medical Biochemistry and Pathology from 2013 to 2017.
Dr. Masson’s team is interested in the DNA repair mechanisms that govern the maintenance of the integrity of our genome, in particular homologous recombination (HR), and related therapeutic avenues. The fundamental part of his work is mainly directed towards the in vitro reconstitution of key HR steps (resection by MRN-RPA-BLM-DNA2-EXO1 complexes and strand invasion with BRCA1-BRCA2-PALB2). Furthermore, his lab is heavily involved in the functional characterization of DNA repair genes using proven biochemical assays and innovative molecular and cellular techniques (BioID, molecular DNA combing, CRISPR-Cas9 system). With his collaborators, he discovered a negative regulation mechanism of the DNA resection step by DYNLL1. Several of the genes studied, including BRCA1, BRCA2 and PALB2, are mutated in breast and ovarian cancer and/or Fanconi anemia, a rare genetic disease characterized by a wide variety of congenital malformations and a risk of acute leukemia and cancer. The laboratory performs a precise characterization of DNA double-strand break repair genes, which is critical for understanding the etiology of these diseases. With a more translational focus, the second part of the research involves developing new synthetic lethal strategies based on the function of certain DNA repair enzymes in collaboration with Dr. Guy Poirier’s team. Its primary objective is to selectively kill breast and ovarian cancer cells using small inhibitory molecules identified by screening chemical libraries. Although PARP inhibitors have demonstrated clinical benefit in patients with germline mutation in BRCA1/2, the emergence of resistance to this type of agent highlights the importance of identifying new combinations of inhibitors. The experiments are performed on 2- and 3-dimensional (spheroids) tumor cell models and mouse models of Fanconi anemia.
Recently, Dr. Masson’s discoveries have led him to join several cancer multi-institutional teams. Among others, he is participating with Dr. Jacques Simard in the PERSPECTIVE I&I (Personalized Risk Assessment for Prevention and Early Detection of Breast Cancer: Integration and Implementation) project, an initiative funded by Genome Canada bringing together the expertise of more than 20 researchers, including several world-renowned fundamentalists, clinicians, and biostatisticians. Within this interdisciplinary group, Dr. Masson’s team is dedicated to developing systematic functional tests to reliably assess the impact of genetic variations linked to breast cancer, especially those affecting PALB2, and determine their clinical relevance for the benefit of patients. The data collected will improve the personalized risk assessment for early detection and more appropriate treatment of breast cancer. In collaboration with the CRCHUM, Dr. Masson also acts as one of the principal investigators of the ONCOPOLE project entitled “Targeting genomic instability as an essential vulnerability of ovarian cancer”, which aims to identify the best therapeutic combinations for eliminating ovarian cancer cells.
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The Genetic and Molecular Analyses of RAD51C and RAD51D Identifies Rare Variants Implicated in Hereditary Ovarian Cancer from a Genetically Unique Population
Journal ArticleCancers (Basel), 14 (9), 2022.
Common Variant in ALDH2 Modifies the Risk of Breast Cancer Among Carriers of the p.K3326* Variant in BRCA2
Journal ArticleJCO Precis Oncol, 6 , 2022.
A DNA repair-independent role for alkyladenine DNA glycosylase in alkylation-induced unfolded protein response
Journal ArticleProc Natl Acad Sci U S A, 119 (9), 2022.
RAD51 protects against nonconservative DNA double-strand break repair through a nonenzymatic function
Journal ArticleNucleic Acids Res, 50 (5), 2022.
Addressing the dark matter of gene therapy: technical and ethical barriers to clinical application
Journal ArticleHum Genet, 141 (6), 2022.
Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging
Journal ArticleJ Vis Exp, (170), 2021.
A functionally impaired missense variant identified in French Canadian families implicates FANCI as a candidate ovarian cancer-predisposing gene
Journal ArticleGenome Med, 13 (1), 2021.
Cockayne syndrome group B protein regulates fork restart, fork progression and MRE11-dependent fork degradation in BRCA1/2-deficient cells
Journal ArticleNucleic Acids Res, 49 (22), 2021.
FAN1 exo- not endo-nuclease pausing on disease-associated slipped-DNA repeats: A mechanism of repeat instability
Journal ArticleCell Rep, 37 (10), 2021.
Starvation-induced proteasome assemblies in the nucleus link amino acid supply to apoptosis
Journal ArticleNat Commun, 12 (1), 2021.
Active projects
- Bourse de soutien aux nouveaux détenteurs de Chaire de recherche du Canada, from 2020-07-01 to 2022-06-30
- Canada Research Chair in DNA repair and Cancer Therapeutics, from 2020-07-01 to 2027-06-30
- Characterization of HR-Killer1 and identification of small molecules for cancer therapy and enhanced gene editing using CRISPR/Cas9-based DNA repair strategies, from 2018-04-01 to 2023-03-31
- Decoding the DNA double-strand break repair pathways: from mechanistic insights to human genome instability diseases, from 2018-07-01 to 2025-06-30
- Grand prix scientifique, from 2022-04-01 to 2023-03-31
- Investigating the Role of RECQL in Breast Cancer Susceptibility, from 2017-04-01 to 2024-03-31
- Patient stratification based on DNA repair functionality for cancer precision medicine, from 2020-01-01 to 2022-12-31
- Personalized Risk Assesment for Prevention and Early Detection of Breast Cancer : Integration and Implementation (PERSPECTIVE II), from 2017-11-01 to 2024-03-31
- Poly(ADP-ribose) writers, readers, and erasers: Functions in DNA double-strand break repair and synthetic lethality, from 2019-10-01 to 2024-09-30
Recently finished projects
- Cibler l’instabilité génomique en tant que vulnérabilité essentielle du cancer de l’ovaire, from 2018-10-01 to 2021-09-30
- Infrastructure for a Tier I CRC in DNA repair and cancer therapeutics, from 2020-07-01 to 2022-01-31
- Rôles des protéines de réparation des cassures double-brin dans la stabilité du génome, l'anémie de Fanconi, et le cancer., from 2016-07-01 to 2020-06-30