Full Professor
Affiliation
Université de Montréal
Research Axes
Team
- Bouchra Boujemla
- Karine Boulay
- Caroline Capdevielle
- Schrodinger Cenatus
- Pault Minaya Ferruzo
- Dagmar Glatz
- Véronica Gueye
- Émilie Hingray
- Mylène Laflamme
- Laurence M. Gagné
- Christina Sawchyn
- Sarah St-Amand
- Roxanne St-Georges
- Romain Villot
Frédérick Antoine Mallette, PhD, heads the Chromatin Structure and Cellular Senescence Research Unit. He is also full professor at the Department of Medicine, and affiliated professor at the Department of Biochemistry and Molecular Medicine at Université de Montréal and the Canada Research Chair in Epigenetics of Aging and Cancer (Tier 2).
The research of Frédérick Antoine Mallette and his team aim to elucidate the molecular mechanisms of cancer formation to identify new pathways that limit tumour progression. The team is interested in senescence (a form of premature cell aging), which provides significant anti-tumour protection. The team also studies genetic defects that inactivate the cell's natural cancer defence mechanisms. In 2023, Frédérick Antoine Mallette published a study in the prestigious scientific journal Cell Reports that led to a better understanding of the molecular causes of pediatric leukemia and opened the door to more effective personalized treatments.
Research Unit
Chromatin Structure and Cellular Senescence
Research interests
- Investigate the role of lysine methylation in senescence and cancer by studying the JUMONJI family of lysine demethylases.
- The regulatory mechanisms of lysine demethylases as well as the biological role of demethylation during different cellular processes including proliferation, transcriptional regulation, the DNA damage response, and tumorigenesis.
- Identify new therapeutic targets to treat cancer. To achieve this goal, the laboratory integrates different systems and approaches [in genomics (ChIP-chip, ChIP-seq, RNA-seq and microarray chips), proteomics (MS/MS), cytology (fluorescent microscopy, immunohistochemical markers), and genetics (cell and mouse lines)] to elucidate the role of demethylases in different biological pathways.
- Analyze the effects of the deregulated expression of demethylases on heterochromatin formation during oncogene-induced senescence (a tumour suppression mechanism).
- Determine the signalling pathways regulated by demethylases and their role in cell transformation.
Publications
Voir toutes les publications-
Crespo-Garcia S., Fournier F., Diaz-Marin R., Klier S., Ragusa D., Masaki L., Cagnone G., Blot G., Hafiane I., Dejda A., Rizk R., Juneau R., Buscarlet M., Chorfi S., Patel P., Beltran P.J., Joyal J.-S., Rezende F., Hata M., Nguyen A., Sullivan L., Damanio J., Wilson A.M., Mallette F.A., David N.E., Gosh A., Tsuruda P.R., Dananberg J., Sapieha P. (2024). Therapeutic targeting of cellular senescence in diabetic macular edema: preclinical and phase 1 trial results. Nature Medicine.
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Neault M., Lebert-Ghali C.-É., Fournier M., Capdevielle C., Garfinkle E.A.R., Obermayer A., Cotton A., Boulay K., Sawchyn C., St-Amand S., Ho K., Assaf B., Mercier F.E., Delisle J.S., Drobetsky E.A., Hulea L., Shaw T.I., Zuber J., Gruber T., Melichar H.J.#, Mallette F.A.# (2023). # denotes co-corresponding authors. CBFA2T3-GLIS2-dependent pediatric acute megakaryoblastic leukemia is driven by GLIS2 and sensitive to Navitoclax. Cell Reports, 113084.
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Villot R., Poirier A., Bakan I., Boulay K., Fernandez E., Devillers R., Gama-Braga L., Gagné A., Caron D., Bérubé J.-S., Bérubé J.-C., Coulombe Y., Orain M., Gélinas Y., Gobeil S., Bossé Y., Masson J.-Y., Elowe S., Bilodeau S., Manem V., Joubert P., Mallette F.A. and Laplante M. (2021) ZNF768 links oncogenic Ras to cellular senescence. Nature Communications. NCOMMS-20-10222-T.
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Crespo-Garcia S., Tsuruda P.R.#, Dejda A., Ryan R.D., Fournier F., Chaney S.Y., Pilon F., Dogan T., Cagnone G., Patel P., Buscarlet M., Dasgupta S., Girouard G., Rao S.R., Wilson A.M., O'Brien R., Juneau R., Guber V., Dubrac A., Beauséjour C., Armstrong S., Mallette F.A., Yohn C.B., Joyal J.-S., Marquess D., Beltran P.J., Sapieha P. # (2021). Pathological angiogenesis in retinopathy engages cellular senescence and is amenable to therapeutic elimination through BCL-xL inhibition. # denotes co-corresponding authors. Cell Metabolism, 33, 1-15.
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Binet F., Cagnone G., Crespo-Garcia S., Hata M., Neault M., Dejda A., Wilson A., Buscarlet M., Mawambo G.T., Howard J.P., Diaz-Marin R., Parinot C., Guber V., Pilon F., Juneau R., Laflamme R., Sawchyn C., Boulay K., Leclerc S., Abu-Thuraia A., Côté J.-F., Andelfinger G., Rezende F.A., Sennlaub F., Joyal J.-S.#, Mallette F.A. #, Sapieha P. # (2020). # denotes co-corresponding authors. Neutrophils extracellular traps target senescent vasculature for tissue remodeling in retinopathy. Science, Aug21; 369(6506):aay5356.
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Sapieha P.# and Mallette F.A.# (2018). # denotes co-corresponding authors. Cellular senescence in post-mitotic cells: Beyond growth arrest. Trends in Cell Biology. 28, 595-607.
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M Gagné, L., Boulay K., Topisirovic I., Huot M.-E.*, Mallette F.A.* (2017) * Equal contribution. Oncogenic Activities of IDH1/2 Mutations: From Epigenetics to Cellular Signaling. Trends in Cell Biology. 27, 738-752.
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Oubaha M., Miloudi K., Dejda A., Guber V., Mawambo G., Germain M.-A., Bourdel G., Popovic N., Rezende F., Kaufman R.J., Mallette F.A.*, Sapieha P.*. (2016) * Contribution égale. Therapeutic inhibition of the senescence-associated secretory phenotype prevents pathological retinal angiogenesis. Science Translational Medicine, 8, 362ra144.
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Carbonneau M, M Gagné L, Lalonde ME, Germain MA, Motorina A, Guiot MC, Secco B, Vincent EE, Tumber A, Hulea L, Bergeman J, Oppermann U, Jones RG, Laplante M, Topisirovic I, Petrecca K, Huot MÉ*, Mallette FA*. (2016) The oncometabolite 2-hydroxyglutarate activates the mTOR signalling pathway. Nature Communications, 7, 12700. * Contribution égale.
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Neault, M., Mallette, F.A.*, and Richard, S.* (2016) miR-137 modulates a tumor suppressor network-inducing senescence in pancreatic cancer cells. Cell Reports, 14, 1966-78. * Contribution égale.
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Neault, M.*, Mallette, F.A.*, Vogel, G., Michaud-Levesque, J. and Richard, S. (2012) Ablation of PRMT6 reveals a role as a negative transcriptional regulator of the p53 tumor suppressor. Nucleic Acids Res, 40, 9513-21. * contribution égale.
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Mallette, F.A. and Richard, S. (2012) JMJD2A Promotes Cellular Transformation by Blocking Cellular Senescence through Transcriptional Repression of the Tumor Suppressor CHD5. Cell Reports, 2, 1233-1243.
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Mallette, F.A., Mattiroli, F., Cui, G., Young, L.C., Hendzel, M.J., Mer, G., Sixma, T.K. and Richard, S. (2012) RNF8- and RNF168-dependent degradation of KDM4A/JMJD2A triggers 53BP1 recruitment to DNA damage sites. EMBO J, 31, 1865-1878.
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Mallette, F.A., Gaumont-Leclerc, M.F. and Ferbeyre, G. (2007) The DNA damage signaling pathway is a critical mediator of oncogene-induced senescence. Genes Dev, 21, 43-48.
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Education
Postdoctoral fellowship
Lady Davis Institute for Medical Research and the Segal Cancer Proteomics Centre, McGill University
PhD
Université de Montréal
Awards
- 2022 Early Career Investigator Award (fundamental research) (University of Montreal / Department of Medicine)
- 2016 Canada Research Chair in Epigenetics of Aging and Cancer (Canadian Institutes of Health Research / CRC))
- 2013 Junior 1 Research Scholar (FRQS)
- 2009 Postdoctoral fellowship (Canadian Institutes of Health Research)
- 2008 Postdoctoral fellowship (National Cancer Institute of Canada / Terry Fox Foundation)
- 2007 Postdoctoral fellowship (FRQS)