Dr. Carlos Stocco
The goal of this R01 application entitled “Regulation of CREB transcriptional activity by AKT downstream pathways in granulosa cells” is to identify the molecular interactions between FSHR and IGF1R signaling downstream of PKA and AKT. Specifically, I would like to elucidate the interactions between CREB, a transcription factor directly downstream of FSH and PKA, and the pathway activated by the IGF1R and AKT. I am a reproductive physiologist with extensive training and broad background in ovarian function. For the last decade, the focus of my research centered on the processes controlling ovarian granulosa cell (GC) function mainly on hormone signaling and activation of genomic pathways regulating female fertility. I believe my work has significantly contributed to the understanding of ovarian physiology in mammals. For these previous studies, I obtained the support of four NIH grants that allowed me to build the groundwork and knowledge for the development of this proposal. My laboratory has gained experience in techniques and methodologies to study ovarian function in vivo using conditional knockout animals and in vitro using molecular tools such as highly efficient silencing and expression systems in primary cultures of human and rodent GCs. I supervised the personnel and administered the budget during the execution of previous grants while simultaneously I performed experiments, carried out data analysis, and wrote manuscripts. I passionately perform these activities which have contributed to building the expertise in ovarian physiology that uniquely qualifies me to lead the research team of this application. In particular, I recruited Dr. Guda, an expert in bioinformatics and biostatistician, who will be instrumental in the development of this project. Novel findings from my laboratory demonstrated that IGFs signaling is obligatory for FSH stimulation of GC differentiation. The current application is the logical continuation of previous and ongoing studies on the interaction between the transcription factors regulated by FSH and IGFs. By elucidating these mechanisms, this proposal will identify indicators of normal follicle development and factors involved in the maintenance of ovarian function and aging.