Grant: Operating Grant

Reproductive dysfunction is a common medical condition that affects the lives of many Canadians. Examples range from abnormalities of sexual development to male and female infertility. Research into these areas is essential for us to understand, diagnose, treat, and hopefully prevent these problems that, for many, can be devastating. Understanding how genes get turned on or off in a correct spatiotemporal manner (being expressed at the right place and at the right time) is central to the study of biological processes in both health and disease. We have been studying the role of a family of transcription factors, called GATA factors, known for their essential function in regulating the development and function of blood cells, the heart, and the immune system. Transcription factors are proteins that bind to specific sequences on DNA where they modulate the expression of target genes. Interestingly, GATA factors are also prominently found in reproductive organs such as the testis and ovary. However, what these factors do in these tissues remain poorly understood. For the past several years, we have focused on the role played by the GATA4 factor. Due to its crucial role in other systems, our hypothesis is that GATA4 is equally important for normal reproductive development and function. Thus, the present research project proposes to study the role of GATA4 in reproductive function by defining its mechanism of action (e.g., identifying its target genes) and by understanding how its expression and activity is regulated in gonadal cells. Moreover, since human GATA4 gene mutations have recently been identified as causative for congenital heart defects, a particular emphasis will be placed on demonstrating a link between GATA4 and human reproductive function. Our ultimate goal is to use this knowledge as groundwork for developing novel therapies that can be used to improve the reproductive health, and therefore the quality of life, of all Canadians.