CLAUDE PERREAULT, M.D., F.R.C.P.(C)
- Principal Investigator, Immunobiology research unit, Institute for Research in Immunology and Cancer
- Full Professor, Department of Medicine, Faculty of Medicine, Université de Montréal
- Hematologist, Maisonneuve-Rosemont Hospital
AWARDS & HONOURS
- Léo-Pariseau Award, Acfas, 2011
- Fellow, Canadian Academy of Health Sciences, 2010–
- Canada Research Chair in Immunobiology, 2004–
- Murray Margarit Memorial Award, Leukemia and Lymphoma Society of Canada, 2009
TRAINING
- AEA in immunogenetics, Université Paris VI, 1980
- Residency in Hematology, Université de Montréal, 1979
- Doctor of Medicine, Université de Montréal, 1975
RESEARCH SUPPORT
- Canadian Cancer Society
- Canadian Institutes of Health Research
- Cole Foundation
- Fonds de la recherche en santé du Québec
- Katelyn Bedard Bone Marrow Association
- Leukemia Lymphoma Society
- Terry Fox Foundation
Trained in hematology and immunogenetics, Claude Perreault is one of the founding members of the Institute for Research in Immunology and Cancer (IRIC), the ranks of which he joined as a Principal Investigator in 2005. In addition to his research and training activities at IRIC, Perreault is a clinical practitioner at Maisonneuve-Rosemont Hospital where he set up both the Histocompatibility Laboratory and the Bone Marrow Transplantion Unit.
Before joining IRIC, Dr. Perreault worked at the Maisonneuve-Rosemont Hospital Research Centre, which he also directed from 1992 through to 2001.
Claude Perreault and his team at IRIC focus their research initiatives on three questions:
•What is the molecular definition of the immune self? Self/non-self discrimination is a fundamental requirement of life. While unicellular eukaryotes primarily employ self/nonself discrimination to avoid self-mating and germline parasitism, multicellular organisms use self/nonself discrimination primarily in immune defence. In a remarkable example of convergent evolution, agnathans and jawed vertebrates have evolved adaptive immune systems based on somatically diversified and clonally expressed Ag receptors. Somatic diversification conveys a decisive advantage in recognition of nonself but comes at a price: some Ag receptors on adaptive lymphocytes happen to be self-reactive. Furthermore, recognition of self has a pervasive influence on the development and function of the immune system because the adaptive lymphocytes of jawed vertebrates are eminently self-referential: they are selected on self-molecules, sustained by self-molecules, and activated in the presence of self-molecules. This raises the fundamental question: what is the molecular definition of self for the adaptive immune system? In our effort to understand the genesis of the immune self, we focus mainly on the self recognized by CD8 T cells, that is, peptides presented by MHC I molecules (the immunopeptidome). We have recently discovered that the immunopeptidome is extremely plastic and that it projects at the cell surface a representation of biochemical networks and metabolic events regulated at multiple levels inside the cell. Since perturbation of a single signaling pathway can lead to significant changes in the composition of the immunopeptidome, cells can communicate their metabolic status to the adaptive immune system. The plasticity of the immunopeptidome has important implications in immunobiology. Depending on the context, inclusion of new peptides in the immunopeptidome can initiate tumor rejection or autoimmunity. Ongoing projects seek to understand how different types of proteasomes and genomic polymorphisms (the genomic self) impact the immunopeptidome (the immune self)This multidisciplinary research program is performed in collaboration with the teams of Pierre Thibault and Sébastien Lemieux.
•Adoptive T-cell immunotherapy (ATCI) of cancer. Allogeneic hematopoietic cell transplantation (AHCT) led to the discovery of the allogeneic graft-versus-leukemia (GVL) effect, which remains the most convincing evidence that immune cells can cure cancer in humans. However, despite its great paradigmatic and clinical relevance, induction of GVL by conventional AHCT remains a quite rudimentary form of leukemia immunotherapy. It is toxic and its efficacy is far from optimal. It is therefore sobering that since the discovery of the GVL effect three decades ago, the way GVL is induced and manipulated has practically not changed. Pre-clinical and clinical studies suggest that injection of T cells primed against a single antigen (Ag) present on neoplastic cells could enhance the GVL effect without causing any toxicity to the host. We therefore contend that Ag-targeted ATCI represents the future of cancer immunotherapy and we are evaluating different strategies to reach this goal. Differences between these strategies hinge on two key elements: the nature of the target Ag and the type of Ag receptor expressed on T cells.
•Homeostasis of thymic epithelial cell progenitors. The thymus, the primary T lymphoid organ in all animals with an adaptive immune system, has both its structure and function remarkably conserved. The conservation of the thymus over 450 million years of evolution and the lack of any thymus equivalent or substitute in the animal kingdom is remarkable when one considers, for instance, that about ten different organs have been used as primary sites of hematopoiesis in gnathostomes. No other organ can compensate for defective thymic function. This is problematic since progressive thymus atrophy ultimately affects all ageing subjects and can even impinge on younger subjects affected by several serious illnesses. Thymus senescence is the most common immunopathology in humans. The rapid and irreversible attrition of thymic epithelial cells is very intriguing considering that other epithelia (skin, GI tract) display an enormous self-renewal potential. We therefore seek to understand the biology of thymic epithelial cell progenitor/stem cells and to elaborate strategies to rejuvenate the thymus.
SELECTED PUBLICATIONS
Caron E, Vincent K, Fortier MH, Laverdure JP, Bramoullé A, Hardy MP, Voisin G, Roux PP, Lemieux S, Thibault P, Perreault C (2011). The MHC I immunopeptidome conveys to the cell surface an integrative view of cellular regulation. Mol Syst Biol,
7:533
Vincent K, Roy DC, Perreault (2011). Next-generation leukemia immunotherapy. Blood, 118:2951-2959
de Verteuil,D, Muratore-Schroeder TL, Granados DP, Fortier MH, Hardy MP, Bramoullé A, Caron E, Vincent K, Mader S, Lemieux S, Thibault P, Perreault C (2010). Deletion of immunoproteasome subunits imprints on the transcriptome and has a broad impact on peptides presented by major histocompatibility complex I molecules. Mol Cell Proteomics 9:2034-2047
Louis J, Heinonen K, Chagraoui J, Vainio S, Sauvageau G, Perreault C (2008). The signaling protein Wnt4 enhances thymopoiesis and expands multipotent hematopoietic progenitors through b-catenin-independent signaling. Immunity; 29: 57-67
Fortier MH*, Caron E*, Hardy MP, Voisin G, Lemieux S, Perreault C‡, Thibault P‡ (2008) The MHC I immunopeptidome is molded by the transcriptome. J Exp Med, 205: 595-610 *Equal contribution. ‡ Equal contribution and corresponding authors.
Baron C, Somogyi R, Greller LD, Rineau V, Wilkinson P, Cho CR, Cameron MJ, Kelvin DJ, Chagnon P, Roy DC, Busque L, Sekaly RP, Perreault C (2007) Prediction of graft-versus-host disease in humans by donor gene-expression profiling. PLoS Med 4:e23
Terra R, Louis I, Le Blanc R, Ouellet S, Zuniga-Pflucker JC, Perreault C (2005) T-cell generation by lymph node resident progenitor cells. Blood 106:193-200
Meunier MC, Delisle JS, Bergeron J, Rineau V, Baron C, Perreault C (2005) T cells targeted against a single minor histocompatibility antigen can cure solid tumors. Nat Med 11:1222-1229
Blais ME, Gerard G, Martinic MM, Roy-Proulx G, Zinkernagel RM, Perreault C (2004) Do thymically and strictly extrathymically developing T cells generate similar immune responses? Blood 103:3102-3110
Fontaine P, Roy-Proulx G, Knafo L, Baron C, Roy DC, Perreault C (2001) Adoptive transfer of minor histocompatibility antigen-specific T lymphocytes eradicates leukemia cells without causing graft-versus-host disease. Nat Med 7:789-794
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