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Frédérick Antoine Mallette
- Professeur titulaire
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Faculté de médecine - Département de médecine
- Professeur accrédité
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Faculté de médecine - Département de biochimie et médecine moléculaire
Profile
Research expertise
Normal cells possess intrinsic mechanisms to avoid genetic mutations that contribute to the formation of cancer. One of these mechanisms is cellular senescence, defined as a permanent cell cycle arrest where the cell remains metabolically active but no longer capable to respond to proliferation stimuli. Methylation of histones plays an important role during senescence by contributing to the stable repression of genes involved in cell cycle progression.
The focus of my research program is to examine the biological role of histone demethylases in different cellular processes including cell cycle, gene regulation, DNA damage response and tumorigenesis. The long-term objective will be to provide a better understanding of the role epigenetic modifications in cancer leading to the development of potential therapeutics in the treatment of cancer.For more information…
Affiliations and responsabilities
Research affiliations
Research units
Titulaire
Membre
- CRHMR — Centre de recherche de l'Hôpital Maisonneuve-Rosemont
- GRUM — Groupe de recherche universitaire sur le médicament
Affiliated institutions
- CIUSSS de l'Est-de-l'Île-de-Montréal – Hôpital Maisonneuve-Rosemont (HMR)
Teaching and supervision
Student supervision
Theses and dissertation supervision (Papyrus Institutional Repository)
Travaux préalables à l’investigation fonctionnelle de la cholestérol-25-hydroxylase (CH25H)
Cycle : Master's
Grade : M. Sc.
Histone lysine methylation reinforces heterochromatin-mediated gene silencing and proliferation arrest during oncogene-induced senescence
Cycle : Doctoral
Grade : Ph. D.
R-2-hydroxyglutarate modulates DNA Replication via Integrated Stress Response
Cycle : Master's
Grade : M. Sc.
Analyzing KDM4A protein interaction network using proximity-dependent biotin identification assay
Cycle : Master's
Grade : M. Sc.
A novel purification method for binder of SPerm proteins and characterization of the protein interaction network of BSPH1
Cycle : Doctoral
Grade : Ph. D.
Knockout mouse model generated by CRISPR technology to study the function of BSP proteins on male fertility in vivo
Cycle : Doctoral
Grade : Ph. D.
Activation de la voie oncogénique mTOR par les formes mutées de l'isocitrate déshydrogénase 1/2 retrouvées chez les gliomes
Cycle : Master's
Grade : M. Sc.
Projects
Research projects
Cholesterol metabolism and regulation of the senescence-associated secretory phenotype in retinopathy
Identifying novel therapeutic vulnerabilities in pediatric acute megakaryoblastic leukemia
Exploiting translational reprogramming in neoplasia to devise unique strategies to eliminate cancer and cancer-promoting senescent cells
Les mécanismes liant la dynamique mitochondriale à l'état de quiescence et à l'activation des cellules souches musculaires
Canada Research Chair in Epigenetics of aging and cancer
Targeting SMOC2-induced epithelial-to-mesenchymal transition inhibits senescence in mouse models of kidney fibrosis
The Terry Fox New Frontiers Program Project Grant in Targeting Metabolic Vulnerabilities in Cancer
Novel function of DEPTOR in regulating the formation of spliceosome in multiple myeloma
Identification of therapeutic targets for pediatric acute megakaryoblastic leukemia
Regulation of chromatin modifiers by metabolites of the Krebs cycle
Les mécanismes liant la dynamique mitochondriale à l'état de quiescence et à l'activation des cellules souches musculaires
Establishing a new class of senolytics to treat age-related pathologies and extending lifespan
Cholesterol metabolism and regulation of the senescence-associated secretory phenotype in retinopathy
Supplément COVID-19 CRSNG_Regulation of chromatin modifiers by metabolites of the Krebs cycle
Oncometabolite-induced chromatin modifications and DNA replication stress in brain cancer
Chaire du Canada - Epigenetics of aging and cancer
THE ROLE OF THE JMJD2 FAMILY OF LYSINIE DEMETHYLASES IN SENESCENCE AND CANCER
FGR-CRSNG_2018-2019
The role of cholesterol metabilsm in cellular senescence and liver cancer
Deciphering the oncogenic properties of cancer-associated IDH1/2 mutations
BINDER OF SPERM (BSP) GENES AND PROTEINS : ROLE OF HUMAN AND MOUSE BSP PROTEINS IN SPERM FUNCTION AND FERTILIZATION
A microcalorimetry system to define the biochemical parameters of molecular interactions
LE ROLE DES DEMETHYLASES DE LYSINES DE LA FAMILLE JUMONJI LORS DE LA SENESCENCE ET DU CANCER
LE ROLE DES DEMETHYLASES DE LYSINES DE LA FAMILLE JUMONJI LORS DE LA SENESCENCE ET DU CANCER
THE ROLE OF LYSINE METHYLATION IN TELOMERE MAINTENANCE
TRANSITION GRANT - COLE FOUNDATION
Publications and presentations
Publications
PUBLICATIONS CHOISIES
- Hajj-Boutros G., Faust A., Muscedere J., Kim P., Amburad N., Chevalier S., Aubertin-Leheudre M., Bergman H., Bowdish D., Burford J., Carrington-Lawrence S., Côté H., Barreto P.d.S., Farrelly C., Fowler R., Gouspillou G., Harrington L., Lautrup S.H., Howlett S., Imani M., Kirkland J., Kuchel G., Mallette F.A., Morais J., Newman J., Pullamn D., Sierra F., Van Raamsdonk J., Rylett J., Duque G. (2024). Navigating the landscape of translational geroscience in Canada: A comprehensive evaluation of current progress and future directions. The Journals of Gerontology - Biological Sciences & Medical Sciences.
- 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.
- 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.
- Pinedo-Carpio E., Dessapt J., Beyneton A., Sacre L., Bérubé M.-A., Villot R., Lavoie E.G., Coulombe Y., Blondeau A., Boulaiw J., Malina A., Luo V., Lazaratos A.-M., Côté J.-F., Mallette F.A., Guarné A., Masson J.-Y., Fradet-Turcotte A., Orthwein A. FIRRM cooperates with FIGNL1 to promote RAD51 disassembly during DNA repair. Science Advances. adf4082
- Bélanger F., Roussel C., Sawchyn C., St-Hilaire E., Gezzar-Dandashi S., Kimenyi Ishimwe A.B., Mallette F.A., Wurtele H., Drobetsky E.A. (2023) A genome-wide screen reveals that Dyrk1A kinase promotes nucleotide excision repair by preventing aberrant overexpression of cyclin D1 and p21. Journal of Biological Chemistry JBC-D-22-02725R1
- Mawambo G., Oubaha M., Crespo-Garcia S., Dejda A., Binet F., Sawchyn C., Sergeev M., Juneau R., Kaufman R.J., Affar E.B., Mallette F.A., Wilson A., Sapieha P. (2023) HIF1a-dependent hypoxia response in myeloid cells requires IRE1a. Journal of Neuroinflammation
- Barbour H., Nkwe N.S., Estavoer B., Messmer C., Gushul-Leclaire M., Villot R., Uriarte M., Boulay K., Hlayhel S., Farhat B., Milot E.#, Mallette F.A.#, Daou S.#, Affar E.B.# (2023) An inventory of crosstalk between ubiquitination and other post-translational modifications in orchestrating cellular processes. # denotes co-corresponding authors. iScience.
- Fournier F., Diaz-Marin R., Pilon F., Neault M., Juneau R., Girouard G., Wilson A.M., Larrivée B., Mallette F.A., Crespo-Garcia S., Sapieha P. (2023) Obesity triggers tumoral senescence and renders poorly immunogenic malignancies amenable to senolysis. PNAS 2022-09973RR
- Lemay J.-F., St-Hilaire E., Gezzar-Dandashi S., McQuaid M., Ronato D.A., Gao Y., Sawchyn C., Bélanger F., Kimenyi Ishimwe A.B., Fortier E., Mallette F.A., Masson J.-Y., Drobetsky E.A., Wurtele H. (2022) A genome-wide screen identifies ScaI as a modulator of the replicative stress response in human cells. PLoS Biology
- Uriarte M., Nkwe N.S., Tremblay R., Ahmed O., Messmer C., Mashtalir N., Barbour H., Masclef L., Voide M., Viallard C., Daou S., Abdelhadi D., Ronato D., Paydar M., Darracq A., Boulay K., Desjardins-Lecavalier N., Sapieha P., Masson J.-Y., Sergeev M., Kwok B.H., Hulea L., Mallette F.A., Milot E., Larrivée B., Wurtele H., Affar E.B. (2021) Liquid phase separation of the mammalian nuclear proteasome links amino acids supply to apoptosis. Nature Communications.
- 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.
- 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.
- 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.
- 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.
- Fernandez E. and Mallette FA. (2016) The rise of FXR1 : escaping cellular senescence in heand and neck squamous cell carcinoma. PLoS Genetics, 12, e1006344.
- 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.
- 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.
- Deschenes-Simard, X., Gaumont-Leclerc, M.F., Bourdeau, V., Lessard, F., Moiseeva, O., Forest, V., Igelmann, S., Mallette, F.A., Saba-El-Leil, M.K., Meloche, S., Mes-Masson, A.M., and Ferbeyre, G. (2013) Tumor suppressor activity of the ERK/MAPK pathway by promoting selective protein degradation. Genes Dev, 27, 900-915.
- 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.
- 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.
- 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.
- Calabrese, V.*, Mallette, F.A.*, Deschenes-Simard, X., Ramanathan, S., Gagnon, J., Moores, A., Ilangumaran, S. and Ferbeyre, G. (2009) SOCS1 links cytokine signaling to p53 and senescence. Molecular Cell, 36, 754-767. * contribution égale.
- 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.
Disciplines
- Biochemistry
- Molecular Biology
- Cell Biology
- Genomics
Areas of expertise
- Genomics
- Cell Signaling and Cancer