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Health Sciences; Natural Sciences and Engineering

Frédérick Antoine Mallette

Professeur titulaire

Faculté de médecine - Département de médecine

Professeur accrédité

Faculté de médecine - Département de biochimie et médecine moléculaire

fa.mallette@umontreal.ca

Secondary numbers: 514 252-3400 #3338 (Laboratoire) 514 252-3400 #3341 (Travail 1)

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.

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Affiliations and responsabilities

Research affiliations

Research units

Titulaire

Membre

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)

Projects

Research projects

2020 - 2027

Cholesterol metabolism and regulation of the senescence-associated secretory phenotype in retinopathy

Lead researcher : Frédérick Antoine Mallette
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXXXXXX-(PJT) Subvention Projet
2024 - 2026

Identifying novel therapeutic vulnerabilities in pediatric acute megakaryoblastic leukemia

Lead researcher : Frédérick Antoine Mallette
2024 - 2026

Exploiting translational reprogramming in neoplasia to devise unique strategies to eliminate cancer and cancer-promoting senescent cells

Lead researcher : Frédérick Antoine Mallette
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXXXXXX-(PJT) Subvention Projet
2023 - 2026

Les mécanismes liant la dynamique mitochondriale à l'état de quiescence et à l'activation des cellules souches musculaires

Lead researcher : Laura Hulea
Co-researchers : Frédérick Antoine Mallette , Mireille Khacho
Funding sources: CRSNG/Conseil de recherches en sciences naturelles et génie du Canada (CRSNG)
Grant programs: PVXXXXXX-Programme NOVA pour chercheur(e)s de la relève (partenariat avec FRQNT)
2021 - 2026

Canada Research Chair in Epigenetics of aging and cancer

Funding sources: SPIIE/Secrétariat des programmes interorganismes à l’intention des établissements
Grant programs: PVX50399-Chaires de recherche du Canada
2020 - 2026

Targeting SMOC2-induced epithelial-to-mesenchymal transition inhibits senescence in mouse models of kidney fibrosis

Lead researcher : Casimiro Gerarduzzi
Co-researchers : Frédérick Antoine Mallette
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXXXXXX-(PJT) Subvention Projet
2019 - 2025

The Terry Fox New Frontiers Program Project Grant in Targeting Metabolic Vulnerabilities in Cancer

Lead researcher : Peter Michael Siegel
Co-researchers : Frédérick Antoine Mallette
Funding sources: TFF/ Terry Fox Foundation/Fondation Terry Fox (La)
Grant programs:
2022 - 2024

Novel function of DEPTOR in regulating the formation of spliceosome in multiple myeloma

Lead researcher : Frédérick Antoine Mallette
Funding sources: SRC/Société de recherche sur le cancer
Grant programs: PVX12154-Subvention de fonctionnement
2018 - 2024

Identification of therapeutic targets for pediatric acute megakaryoblastic leukemia

Lead researcher : Frédérick Antoine Mallette
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXXXXXX-(PJT) Subvention Projet
2017 - 2024

Regulation of chromatin modifiers by metabolites of the Krebs cycle

Lead researcher : Frédérick Antoine Mallette
Funding sources: CRSNG/Conseil de recherches en sciences naturelles et génie du Canada (CRSNG)
Grant programs: PVX20965-(RGP) Programme de subvention à la découverte individuelle ou de groupe
2023

Les mécanismes liant la dynamique mitochondriale à l'état de quiescence et à l'activation des cellules souches musculaires

Lead researcher : Laura Hulea
Co-researchers : Frédérick Antoine Mallette , Mireille Khacho
Funding sources: FRQNT/Fonds de recherche du Québec - Nature et technologies (FQRNT)
Grant programs: PVXXXXXX-Programme NOVA pour chercheur(e)s de la relève (partenariat avec CRSNG)
2019 - 2023

Establishing a new class of senolytics to treat age-related pathologies and extending lifespan

Lead researcher : Frédérick Antoine Mallette
Co-researchers : Ivan Topisirovic
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXX5647-(MOP) Subvention de fonctionnement incluant les subventions de fonctionnement programmatiques (général)
2020 - 2021

Cholesterol metabolism and regulation of the senescence-associated secretory phenotype in retinopathy

Lead researcher : Frédérick Antoine Mallette
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXXXXXX-(PJT) Subvention Projet
2020 - 2021

Supplément COVID-19 CRSNG_Regulation of chromatin modifiers by metabolites of the Krebs cycle

Lead researcher : Frédérick Antoine Mallette
Funding sources: CRSNG/Conseil de recherches en sciences naturelles et génie du Canada (CRSNG)
Grant programs: PVXXXXXX-Supplément à l’appui des étudiants, des stagiaires postdoctoraux et du personnel de soutien à la recherche COVID-19
2019 - 2021

Oncometabolite-induced chromatin modifications and DNA replication stress in brain cancer

Lead researcher : Hugo Wurtele
Co-researchers : Frédérick Antoine Mallette
Funding sources: SRC/Société de recherche sur le cancer
Grant programs: PVX12154-Subvention de fonctionnement
2016 - 2021

Chaire du Canada - Epigenetics of aging and cancer

Lead researcher : Frédérick Antoine Mallette
Funding sources: SPIIE/Secrétariat des programmes interorganismes à l’intention des établissements
Grant programs: PVX50399-Chaires de recherche du Canada
2014 - 2021

THE ROLE OF THE JMJD2 FAMILY OF LYSINIE DEMETHYLASES IN SENESCENCE AND CANCER

Lead researcher : Frédérick Antoine Mallette
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXX5647-(MOP) Subvention de fonctionnement incluant les subventions de fonctionnement programmatiques (général)
2018 - 2019

FGR-CRSNG_2018-2019

Lead researcher : Frédérick Antoine Mallette
Co-researchers : Pierre Belhumeur
Funding sources: CRSNG/Conseil de recherches en sciences naturelles et génie du Canada (CRSNG)
Grant programs: PVXXXXXX-FGR - Subvention de recherche institutionnelle
2017 - 2019

The role of cholesterol metabilsm in cellular senescence and liver cancer

Lead researcher : Frédérick Antoine Mallette
Co-researchers : Subburaj Ilangumamran
Funding sources: SRC/Société de recherche sur le cancer
Grant programs:
2017 - 2019

Deciphering the oncogenic properties of cancer-associated IDH1/2 mutations

Lead researcher : Frédérick Antoine Mallette
Funding sources: Terry Fox Research Institute
Grant programs:
2013 - 2019

BINDER OF SPERM (BSP) GENES AND PROTEINS : ROLE OF HUMAN AND MOUSE BSP PROTEINS IN SPERM FUNCTION AND FERTILIZATION

Lead researcher : Puttaswamy Manjunath , Frédérick Antoine Mallette
Funding sources: IRSC/Instituts de recherche en santé du Canada
Grant programs: PVXX5647-(MOP) Subvention de fonctionnement incluant les subventions de fonctionnement programmatiques (général)
2016 - 2018

A microcalorimetry system to define the biochemical parameters of molecular interactions

Lead researcher : El Bachir Affar
Funding sources: CRSNG/Conseil de recherches en sciences naturelles et génie du Canada (CRSNG)
Grant programs: PVXXXXXX-(OIR) Outils et d'instruments de recherche (de 7 001 $ à 150 000 $)
2013 - 2016

LE ROLE DES DEMETHYLASES DE LYSINES DE LA FAMILLE JUMONJI LORS DE LA SENESCENCE ET DU CANCER

Lead researcher : Frédérick Antoine Mallette
Funding sources: FRQS/Fonds de recherche du Québec - Santé (FRSQ)
Grant programs: PVXXXXXX-Établissement de jeunes chercheurs Juniors 1
2013 - 2016

LE ROLE DES DEMETHYLASES DE LYSINES DE LA FAMILLE JUMONJI LORS DE LA SENESCENCE ET DU CANCER

Lead researcher : Frédérick Antoine Mallette
Funding sources: FRQS/Fonds de recherche du Québec - Santé (FRSQ)
Grant programs: PVXXXXXX-Bourse de chercheur-boursier : Junior 1
2013 - 2015

THE ROLE OF LYSINE METHYLATION IN TELOMERE MAINTENANCE

Lead researcher : Frédérick Antoine Mallette
Funding sources: SRC/Société de recherche sur le cancer
Grant programs:
2013 - 2015

TRANSITION GRANT - COLE FOUNDATION

Lead researcher : Frédérick Antoine Mallette
Funding sources: COLE Foundation/Fondation Cole
Grant programs:

Outreach

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 NavitoclaxCell 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 IRE1aJournal 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 retinopathyScience, 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