CLAUDE PERREAULT, M.D., F.R.C.P.(C)
- Principal Investigator, Immunobiology Laboratory, Institute for Research in Immunology and Cancer
- Full Professor, Department of Medicine, Faculty of Medicine, Université de Montréal
- Hematologist, Maisonneuve-Rosemont Hospital
AWARDS & HONOURS
- 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 as a hematologist, 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 Transplant 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 are the mechanisms responsible for the development of T-lymphocytes? The reason why the thymus is the primary T lymphoid organ in all animals with an adaptive immune system remains largely unknown. This is problematic since progressive thymus atrophy ultimately affects all ageing subjects and can even impinge on younger subjects affected by several serious illnesses. Thymic involution is implicated in the age-related increase in the incidence of infections, autoimmune disorders and cancer. Therefore, we want to determine whether i)T cells produced extrathymically can substitute for canonical T cells and ii) it is possible to enhance thymic function. We have reported that transgenic expression or injection of Oncostatin M (OM) induces a massive production of T cells in lymph nodes (LNs) that ectopically recapitulates all the development stages normally found in the thymus. OM induces a COX-2-dependent angiogenesis of high endothelial venules that entails a massive accumulation of lymphoid progenitors in LNs. Furthermore, OM increases the clonogenic potential of LN-resident lymphoid progenitors. However, even though OM-transgenic mice have no CD4 or CD8 T-cell lymphopenia, their extrathymic T cells are functionally deficient and cannot substitute for thymus-derived T cells. We are now trying to uncover why extrathymic T cells are less fit than classic thymus-derived T cells. In addition, we found that overexpression of Wnt4 in hematopoietic cells of adult mice enhanced thymopoiesis. Thymic cellularity was decreased in Wnt4–/– mice and increased when Wnt4 was overexpressed. In both models, the key effect of Wnt4 was on the numbers of thymic early thymic progenitors (ETPs). The influence of Wnt4 on hematolymphoid progenitors was mediated by the noncanonical pathway. It will therefore be of considerable interest to determine whether impairment of noncanonical Wnt signaling may underlie HSC senescence and thymic involution and whether these processes can be reverted by provision of Wnt4.
• What is the molecular definition of the immune self, How is it molded? And how is it influenced by neoplastic transformation? Studies in mice and humans have clearly shown that the immune system can kill cancer cells, including cancer stem cells that are resistant to chemo and radiotherapy. The goal of this project is to discover how the immune system can distinguish cancer cells from normal cells and to determine how those differences could be exploited to cure cancer. We discovered that each cancer cell presents more than 10 abnormal molecules that can be recognized by the immune system (these molecules are then said to be immunogenic). Most abnormal immunogenic molecules present on cancer cells derive from proteins that contribute to the proliferation and survival of neoplastic cells. First and foremost, our studies will provide us with a rational strategy to develop preventive and therapeutic vaccines against cancer. In addition, they will help us to understand how neoplastic transformation impinges on protein metabolism. Finally, since we have shown that cytotoxic T-lymphocytes–cells can selectively eliminate cancer cells in mice, we are currently setting out to explore the potential of this approach with human beings.
• How does the TGF-beta pathway induce and maintain tolerance. We recently found that SMAD3, a key component of the TGF-beta pathway regulates the induction and maintenance of tolerance to self as well as to transplanted allogeneic cells. Our objectives are now i) to find how SMAD3 orchestrates tolerance and ii) to evaluate whether modulation of SMAD3 can be used to induce transplantation tolerance and to abrogate tolerance to cancer cells.
SELECTED PUBLICATIONS
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 2008; 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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