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B.S., Banaras Hindu University, India
M.S., Banaras Hindu University, India
Ph.D., Banaras Hindu University, India
Postdoctoral Research Fellow, Academia Sinica, Taiwan
Postdoctoral Fellow, Morehouse School of Medicine
My research focus on a broad spectrum of cellular, molecular and physiological approaches to investigate the mechanisms underlying hormone signaling and action in the hypothalamic-pituitary-ovarian axis. Ovarian folliculogenesis in mammals is a complex process involving interactions between germ and somatic cells. Gonadotropins dependent orchestrated expression of transcription factors, cell adhesion molecules and growth factors are required for success of development of ovarian follicles and ovulation. We have recently identified a novel epidermal growth factor (EGF) family member, Neuregulin-1 (NRG1) in the rat pre-ovulatory granulosa cells (PO-GC) and follicles. We also have located the accumulation of NRG1 in the preovulatory follicular fluid. Our unpublished data also demonstrated that the mRNA and protein levels of NRG1 in the PO-GC and follicles were differentially expressed in relation to gonadotropin stimulation. LH-induced ovulation is similar to an inflammatory response. NRG1 is known to have neuroprotective and anti-inflammatory properties. NRG1 and its tyrosine kinase receptor (ErbB-2, -3 and -4) signaling are best known for their indispensable role in proliferation, differentiation, and survival of cardiac and neuronal development. The function of NRG1 during follicular development is yet to be defined. The gonadotropin induced NRG1 accumulation in the follicular fluid suggests a possible role as an autocrine and/or paracrine mechanism of action as an anti-inflammatory factor in granulosa cells survival. Furthermore, our in vitro studies using a chemotherapy-induced apoptotic model revealed that exogenous NRG1 treatment suppressed the cleavage of caspase-3 and delayed the onset of apoptosis in PO-GCs. Moreover, our unpublished studies also demonstrated that mice with NRG1 gene knockout are sexually immature. Taken together these results provide novel evidence that NRG1 may play an important role in PO-GC differentiation and survival in pre-ovulatory follicle. On the basis of these findings, currently, we are focusing our research to understand the ovarian NRG1-ErbB receptor signaling mediates PO-GCs survival, which affects follicular maturation.
Moreover, understanding the intracellular signaling pathways utilized by the NRG1 in governing folliculogenesis is likely to help identify strategies to overcome ovarian dysfunction. Infertility is a significant and prevalent health problem, affecting approximately 12% of the reproductive age population. More than 1 out of 10 couples experience infertility and about a third of infertility problems are due to ovarian dysfunction. Ovulation is the unique biological process by which a mature oocyte and surrounding cumulus cells are released from the surface of the ovary. This LH-induced process is similar to an inflammatory response and requires the expression of specific genes (the EGF-like factors (Areg, Ereg, Btc), matrix factors and cytokines) including NRG1. The use of NRG1 as a cellular protective agent in ovarian dysfunction may prevent follicular/ovarian disorders. Ultimately, create a framework for developing new strategies to better understand NRG1 and receptor ErbB1-4 signaling in ovarian dysfunction.
- Understand the molecular basis of program cell death
- Understand the molecular basis of gametogenesis (folliculogenesis)
- Understand the molecular basis of ovarian and breast cancer progression
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