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| Robert Viger |
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Research Interests:
Summary of Results: Reproductive dysfunction is a common medical condition that affects the lives of many individuals. Problems range from abnormalities of sexual development to male and female infertility. Research in these areas is essential for us to understand, diagnose, treat, and hopefully prevent these problems that for many can be devastating. My laboratory seeks to understand the molecular and genetic mechanisms involved in human reproduction in both health and disease. Our goal is to provide the necessary groundwork for developing novel therapies that can eventually be used to improve the reproductive health and therefore the quality of life in our society. For the past several years, our research has focused on better understanding the role of the GATA family of transcription factors in gonadal function. The GATA family of factors is composed of six zinc finger DNA-binding proteins (named GATA1 to GATA6) that recognize the consensus DNA sequence WGATAR found in the regulatory region of several genes required for the differentiation and/or morphogenesis of numerous vital organs. These factors were first identified as major developmental determinants of both the hematopoietic and cardiac systems. Today, they are known to be expressed in a wide variety of tissues where they act as critical regulators of developmental- and cell-specific gene expression. This includes multiple endocrine organs such as the pituitary, pancreas, adrenals, and especially the gonads. Due to their well-established developmental roles in other systems, we have proposed that GATA transcription factors play equally important roles in regulating gonadal development and function. Indeed, over the past few years, we have broadened the scope of GATA action to include early testis development, male sex differentiation, and steroidogenesis. Insights into the roles played by GATA factors in the gonads have been greatly aided by the characterization of novel GATA-dependent genes identified by us and other groups. This growing list includes genes that code for hormones and their receptors (AMH/MIS, inhibin a, FSH receptor), components of the steroidogenic pathway (StAR, 3b-HSD, P450 aromatase, 17a-hydroxylase), and transcription factors (SRY, SOX9, DMRT1). Interestingly, aberrant GATA function has now begun to be linked with human disease, and we believe that the reproductive system will be no exception. Our research into the role of the GATA family of transcription factors in reproductive function has already led to the potential implication of these factors in several human syndromes and/or pathologies such as breast cancer, endometriosis, polycystic ovarian syndrome, and phenotypic sex reversal associated with insufficient AMH expression. Our ultimate goal is to hopefully translate our work into promising new therapies for the treatment and prevention of these pathologies and other diseases that affect reproductive health. Lab Members:
List of publications (since 2003) : Bouchard MF, Taniguchi H, Viger RS 2008 The effect of human GATA4 gene mutations on the activity of target gonadal promoters. J Mol Endocrinol, epub Miyamoto Y, Taniguchi H, Hamel F, Silversides DW, Viger RS 2008 A GATA4/WT1 cooperation regulates transcription of genes required for mammalian sex determination and differentiation. BMC Mol Biol 9:44 Pilon N, Raiwet D, Viger RS, Silversides DW 2008 Novel pre- and post-gastrulation expression of Gata4 within cells of the inner cell mass and migratory neural crest cells. Dev Dyn 237:1133-43 Viger RS, Mazaud Guittot S, Anttonen M, Wilson DB, Heikinheimo M 2008 Role of the GATA family of transcription factors in endocrine development, function, and disease. Mol Endocrinol 22:781-98 Mazaud Guittot S, Tetu A, Legault E, Pilon N, Silversides DW, Viger RS 2007 The proximal Gata4 promoter directs reporter gene expression to Sertoli cells during mouse gonadal development. Biol Reprod 76:85-95 Robert NM, Miyamoto Y, Taniguchi H, Viger RS 2006 LRH-1/NR5A2 cooperates with GATA factors to regulate inhibin a-subunit promoter activity. Mol Cell Endocrinol 257-258:65-74 Bouchard MF, Taniguchi H, Viger RS 2005 Protein kinase A-dependent synergism between GATA factors and the nuclear receptor, liver receptor homolog-1 (LRH-1), regulates human aromatase (CYP19) PII promoter activity in breast cancer cells. Endocrinology 146:4905-16 Viger RS, Silversides DW, Tremblay JJ 2005 New insights into the regulation of mammalian sex determination and male sex differentiation. Vitam Horm 70:387-413 Dufresne J, St-Pierre N, Viger RS, Hermo L, Cyr DG 2005 Characterization of a novel rat epithelial cell line to study epididymal function. Endocrinology 146:4710-20. Taniguchi H, Martin LJ, Robert NM, Simard J, Tremblay JJ, Viger RS 2005 GATA factors and the nuclear receptors SF-1/LRH-1 are key mutual partners in the regulation of human HSD3B2 promoter. Mol Endocrinol 19:2358-70 Viger RS, Taniguchi H, Robert NM, Tremblay JJ 2004 Role of the GATA family of transcription factors in andrology. J Androl 25:441-52 Viger RS, Silversides DW 2004 Genes and gene defects affecting gonadal development and sex determination. In: Encyclopedia of Endocrine Diseases, L Martini (ed.), Elsevier Academic Press, vol. 2, pp 135-140 Tremblay JJ, Viger RS 2003 A mutated form of steroidogenic factor 1 (SF-1 G35E) that causes sex reversal in humans fails to synergize with transcription factor GATA-4. J Biol Chem 278:42637-42642 Tremblay JJ, Viger RS 2003 Transcription factor GATA-4 is activated by phosphorylation of serine 261 via the cAMP/protein kinase A signaling pathway in gonadal cells. J Biol Chem 278:22128-22135 Tremblay JJ, Viger RS 2003 Novel roles for GATA transcription factors in the regulation of steroidogenesis. J Steroid Biochem Mol Biol 85:291-8 Pilon N, Daneau I, Paradis V, Hamel F, Lussier JG, Viger RS, Silversides DW 2003 Porcine SRY promoter is a target for steroidogenic factor 1. Biol Reprod 68:1098-106
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