Frédérick Antoine Mallette

Office Phone: (514)252-3400 poste 3341
Fax: (514)252-3430
Lab Phone: (514)252-3400 poste 3338
fa.mallette@umontreal.ca

Research Axis  Immunology-Oncology
Research Unit  Chromatin structure and cellular senescence

TitLE

    • Assistant Professor

EDucation

    • Postdoctoral Fellowship  2008-2012, Lady Davis Institute and Segal Cancer, McGill University 
    • Ph.D. 2001-2008, Université de Montréal  

DISTINCTIONS and Achievements

    • Canada Research Chair in Epigenetics of Aging and Cancer, 2016-2021
    • Research Scholar Junior I, Fonds de recherche du Québec - Santé, 2013-2016
    • Postdoctoral Fellowship, Canadian Institutes of Health Research, 2009-2012
    • Postdoctoral Fellowship, National Cancer Instituteof Canada/ Terry Fox Foundation, 2008-2009
    • Postdoctoral Fellowship, Fonds de recherche en santé du Québec, 2007-2008

      RESEARCH TEAM

      Ph.D Student

      • Erlinda Fernández-Diáz, M.Sc.
      • Christina Sawchyn, M.Sc.

      Research Assistant

      • Marine Regnier, M.Sc.

      Research Agent

      • Florence Couteau, Ph.D.

      Research Interests

      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. We now propose to investigate the role of chromatin structure and histone lysine methylation during senescence and cancer by studying the JUMONJI family of lysine demethylases.

      The focus of my research program is to examine the regulation of histone demethylases and the biological role of histone demethylation 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 of protein demethylation in cancer leading to the development of potential therapeutics in the treatment of cancer. To this end, the laboratory will integrate several different approaches and systems to elucidate the crucial roles of histone demethylases in biological pathways. Using genomic (ChIP-chip, ChIP-seq, RNA-seq and microarrays), proteomic (MS-MS), cytological (fluorescence microscopy, immunohistochemistry), and genetic (cell lines and mouse) approaches, we will further investigate the role of histone demethylases in the DNA damage response and their impact on the recruitment of different DNA repair factors. Furthermore, the impact of the deregulated expression of demethylases in heterochromatin formation and oncogene-induced senescence (a tumor suppressive cell response) will be studied. I am also interested in the signaling pathways regulating activity of histone demethylases and their role in cellular transformation.

      This research will shed light not only on chromatin modifications underlying tumor suppression and cellular transformation, but also lead to the development of promising therapeutic strategies against cancer.

      Selected Papers  

      • 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.

      Complete list of Dr F.A. Mallette's publication (PubMed)   

      ADDITIONAL INFORMATIONS 

      Grants

        • Hôpital Maisonneuve-Rosemont Foundation  
        • Cole Foundation
        • Fonds de Recherche du Québec - Santé (FRQS)
        • Cancer Research Society
        • Canadian Institutes of Health Research (CIHR)
        • Canada Research Chairs program