Les cellules normales possèdent des mécanismes intrinsèques de suppression tumorale permettant d’éviter l’apparition de mutations génétiques contribuant à la formation de cancers. La sénescence cellulaire s’oppose au processus de transformation et se définit comme un arrêt permanent du cycle cellulaire durant lequel la cellule demeure métaboliquement active mais insensible aux stimuli de prolifération. La méthylation des histones joue un rôle crucial lors de la sénescence en permettant la répression stable de gènes impliqués dans la progression du cycle cellulaire.

Nous proposons donc d’investiguer la fonction biologique des déméthylases des histones lors de différents processus cellulaires dont le cycle cellulaire, la régulation de l’expression génique la réponse aux dommages à l’ADN ainsi que la tumorigénèse. L’objectif de nos recherches est d’élucider le rôle des modifications épigénétiques dans le cancer afin de développer de nouvelles thérapies contre le cancer.

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.