The considerable research effort in my laboratory has been directed to identifying the factors that play crucial roles in these periovulatory processes and delineating their specific actions in the ovary using rodents and human models. The periovulatory process is initiated by the midcycle gonadotropin (LH/FSH) surge that induces the extensive reprogramming of gene expression in periovulatory follicles. Transcription factors induced by the LH surge in the preovulatory follicles play a central role in these processes by directly controlling the expression of periovulatory genes.
Of particular interest in our laboratory has been on a group of transcription factors, such as Core Binding Factor (CBF/RUNX), Activator Protein-1 (AP-1), Progesterone receptor (PGR), and Glucocorticoid receptor (NR3C1). Research in my laboratory has revealed that the expression of these transcription factors is highly up-regulated in ovulatory follicles after the LH surge that initiates the ovulatory cascade in the ovary of rodents and humans. To determine the functional impact of these transcription factors, we have generated several lines of tissue-specific mutant mice deficient in these genes in the ovary. Importantly, we found that mice deficient of Runx transcription factors (Cbfbflox/flox;Esr2Cre/+;Runx2flox/flox)(See below) and the AP-1 transcription factors (Fosflox/flox; Junbflox/flox; Esr2Cre/+) exhibited complete blockage of ovulation and corpus luteum formation, resulting in infertility. These results demonstrated the physiological significance of these transcription factors in normal ovarian function, specifically in the ovulatory process and corpus luteum formation.
We have several exciting projects in the laboratory. These projects include the investigation of:
1) The role of the AP-1 transcription factors in the ovary.
2) The role of progesterone receptors in the ovary.
3) The role of Glucocorticoid and its receptors in the ovary.
4) The role of immune cells in the ovulatory process and corpus luteum formation
5) Regulatory mechanisms involved in progesterone and glucocorticoid production and metabolism in the periovulatory follicle.
The identification of novel mechanism(s) regulating steroid production and metabolism and the actions of their nuclear receptors (e.g., progesterone receptor and glucocorticoid receptor) will greatly improve our understanding of steroidogenesis and tissue-specific regulation of steroids.