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Our unpublished data also demonstrated that the mRNA and protein levels of NRG1 in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 Moreover, our unpublished studies also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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