Bouchard, Maxime - McGill University - Department of Biochemistry

研究领域

Development and cancer of the urogenital system The formation of the renal and genital systems during embryonic development involves complex molecular and cellular events. A failure to perform these cellular functions is responsible for the high frequency of urogenital malformations found in newborn (about 1:500). Interestingly, the genes involved in key steps of embryonic development are often also involved in tumor formation later on. We are interested in the molecular networks regulating processes such as cell lineage specification, epithelialization and epithelial integrity, tubular extension, apoptotic morphogenesis and proliferation control. We tackle these important questions using a combination of mouse genetics, tissue and cell culture as well as molecular and biochemical assays. 1- Transcriptional network of urogenital system (UGS) development. A number of transcription factors have been involved in the formation of the urogenital system. We are focusing on the transcriptional network controlled by Gata3, Pax2 and Pax8 at different steps of UGS development. We have previously shown the role of Pax genes in nephric lineage specification, branching morphogenesis and nephron differentiation. We also demonstrated the requirement for Gata3 in proliferation control, duct elongation and guidance as well as tubular homeostasis. We are pursuing these studies to identify the key molecules mediating these cellular functions downstream of Pax and Gata factors. 2- Receptor protein tyrosine phosphatases in distal ureter maturation. We have recently described the process by which the ureter connects to the bladder during embryonic development (distal ureter maturation). Interestingly, this process involves the elimination of a cell population by programmed cell death. We further identified LAR-family receptor protein phosphatases (PTPRF and PTPRS) as necessary for this process. We are currently pursuing the characterization of the role of LAR-family phosphatases in apoptosis-mediated morphogenesis. 3- Urogenital cancer. Over the years, it has become clear that several genes required for normal embryonic development are also involved in tumor formation after birth. Another ongoing interest of the lab is to understand the contribution of Pax and Gata transcription factors and their transcriptional targets in urogenital tissue neoplasia.

近期论文

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Uetani, N., Bertozzi, K., Chagnon, M.J., Hendriks, W., Tremblay, M.L. and Bouchard, M. (2009) Maturation of ureter-bladder connection by LAR receptor protein-tyrosine phosphatases. Journal of Clinical Investigation. 119(4):924-35. Dydensborg, A.B., Rose, A., Grote, D., Paquet, M., Siegel, P. and Bouchard, M. (2009) GATA3 prevents breast cancer growth and metastasis to the lung. Oncogene 28(29):2634-42. Nguyen, A.H., Béland, M., Gaitan, Y. and Bouchard, M. (2009) A novel CalcineurinA binding protein is overexpressed in Wilms’ tumor and promotes cell migration. Molecular Cancer Research 7(6):821-31. Grote, D., Souabni, A., Merkel, C., Chi, X., Boualia, S.K., Costantini, F., Carroll, T. and Bouchard, M. (2008) Gata3 Acts Downstream of beta-Catenin Signaling to Prevent Ectopic Metanephric Kidney Induction. PLOS Genetics Dec;4(12):e1000316. Epub 2008 Dec 26. Cadieux, C., Harada, R., Paquet, M., Côté, O., Trudel, M., Nepveu, A. and Bouchard M. (2008) Polycystic kidneys caused by sustained expression of CUX1 isoform p75. Journal of Biological Chemistry 283(20):13817-13824. Narlis, M., Grote, D., Boualia, S.K., Gaitan, Y. and Bouchard, M. (2007). Pax2 and Pax8 regulate branching morphogenesis and nephron differentiation in the developing kidney. Journal of the American Society of Nephrology 18(4):1121-1129 Gaitan, Y., Bouchard, M. (2006) Expression of the delta-protocadherin Pcdh19 in the developing mouse embryo. Gene Expression Patterns. 6, 893-899. Grote, D., Souabni, A, Busslinger, M. and Bouchard, M. (2006) Pax2/8-regulated Gata3 expression is necessary for morphogenesis and guidance of the nephric duct in the developing kidney. Development 133, 53-61.