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Viger

Robert S. Viger, Ph.D.

Professor

Laval University

Department of Obstetrics, Gynecology and Reproduction

2705 Laurier Blvd., Room T3-67

Centre de recherche du CHU de Québec

Québec (Québec) G1V 4G2

CANADA

Tel.: (418) 656-4141 x46159

Fax: (418) 654-2783

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Research Interests:

  • Molecular endocrinology
  • Gene expression and regulation
  • Transcriptional regulation
  • Gonadal development
  • Sex determination and differentiation
  • Testicular physiology
  • Sertoli cell function

 

Description of research:

Reproductive dysfunction is a common medical condition. Problems range from differences in the sex determination and differentiation pathways to male and female infertility. Research in these areas is therefore essential for us to understand, diagnose, treat, and hopefully prevent these problems that for many individuals and couples can be devastating. My laboratory seeks to understand the molecular and genetic mechanisms involved in human and animal 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 reproductive health and therefore the quality of life of those affected.

My laboratory is specifically interested in defining the transcriptional regulatory pathways that are involved in establishing mammalian sex determination (i.e., the formation of a testis or an ovary) and sex differentiation (i.e., the development of internal and external genitalia and therefore the male or female phenotype). We are also interested in understanding the transcriptional control of gonadal gene expression, especially in the somatic cell types of the testis (Sertoli cell, Leydig cell) where we have the most expertise. Over the past several years, our main focus has been to understand the physiological roles played by members of the GATA family of transcription factors. 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 now the gonads. Using basic molecular biology methodologies (promoter characterization studies) and various cell line models, we have contributed significantly to better understanding what genes and gene networks these factors target and regulate. Indeed, the scope of GATA action has broadened to include early gonadal development, sex differentiation, and steroidogenesis. GATA factors and in particular GATA4 regulate a plethora of genes that play essential roles throughout gonadal ontogeny. These include those expressed early in gonadal development (Sry, Sox9, Amh, Dmrt1) and those acting later in the fetal and adult gonads (Inha, Star, Cyp11a1, Cyp19a1, and many others). We have recent evidence that GATA4 is a master regulator of steroidogenesis where its actions are akin to that of the nuclear receptor SF-1/NR5A1. Interestingly, aberrant GATA function is known to be linked with some human diseases, and we believe that the reproductive system will be no exception. 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.

Moving forward, we are now keenly interested in defining 1) the subset of GATA regulated genes that are direct targets for GATA factors (i.e., those that require direct GATA binding) and 2) how the GATA genes themselves are regulated both at the transcriptional (GATA gene structure and promoter activity) and post-translational levels. The classical molecular biology techniques that we have relied upon in the past have imposed severe limitations on addressing our new set of questions. My laboratory has recently adopted and employed the CRISPR/Cas9 genome editing technology to generate a series of novel point mutations in the mouse that target either GATA4 post-translational modifications or specific GATA-binding motifs in select target genes. The application of genome-editing technology using CRISPR/Cas9 has opened the door to move beyond simple gene regulation studies in reproduction by allowing for the direct analysis of target genes and more importantly, the establishment of more precise hierarchical gene regulatory networks.

 

Current Lab Members:

Marie-France Bouchard Research Assistant This email address is being protected from spambots. You need JavaScript enabled to view it.
Francis Bergeron Research Assistant This email address is being protected from spambots. You need JavaScript enabled to view it.
Vanessa Théberge Grad Student This email address is being protected from spambots. You need JavaScript enabled to view it.

 

List of publications (since 2003) :

Bergeron F, Nadeau G, and Viger RS. 2015 GATA4 knockdown in MA-10 Leydig cells identifies multiple target genes in the steroidogenic pathway. Reproduction 149:245-257.

George RM, Hahn KL, Rawls A, Viger RS, Wilson-Rawls J. 2015 Notch signaling represses GATA4-induced expression of genes involved in steroid biosynthesis. Reproduction 150:383-94.

Mazaud-Guittot S, Prudhomme B, Bouchard MF, Bergeron F, Daems C, Tevosian SG, Viger RS. 2014 GATA4 autoregulates its own expression in gonadal cells via its distal 1b promoter. Biol Reprod 90:25.

Boulende Sab A, Bouchard MF, Béland M, Prud'homme B, Souchkova O, Viger RS, Pilon N.An Ebox element in the proximal Gata4 promoter is required for Gata4 expression in vivo.PLoS One. 2011;6(12):e29038.

Martin LJ, Bergeron F, Viger RS, Tremblay JJ. Functional cooperation between GATA factors and cJUN on the star promoter in MA-10 Leydig cells.J Androl. 2012;33:81-7.

Nel-Themaat L, Jang CW, Stewart MD, Akiyama H, Viger RS, Behringer RR. Sertoli cell behaviors in developing testis cords and postnatal seminiferous tubules of the mouse.Biol Reprod. 2011;84:342-50.

Mazaud Guittot S, Bouchard MF, Robert-Grenon JP, Robert C, Goodyer CG, Silversides DW, Viger RS. Conserved usage of alternative 5' untranslated exons of the GATA4 gene.PLoS One. 2009;4(12):e8454.

Taniguchi H, Komiyama J, Viger RS, Okuda K. The expression of the nuclear receptors NR5A1 and NR5A2 and transcription factor GATA6 correlates with steroidogenic gene expression in the bovine corpus luteum. Mol Reprod Dev. 2009;76:873-80.

Bouchard MF, Taniguchi H, Viger RS. The effect of human GATA4 gene mutations on the activity of target gonadal promoters. J Mol Endocrinol. 2009;42:149-60.

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