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ALIGNED RESEARCH FOCUS
Children’s health and women’s health
ORGAN SYSTEM/DISEASE FOCUS
My research focuses on elucidating the function of GnRH neurons and the mechanism of puberty onset. Because it is difficult to conduct cellular and molecular studies in humans, some years ago we developed an excellent non-human primate model with a primary cell culture system in vitro and a direct measurement of GnRH in vitro. More recently, we have established a reliable method to generate human GnRH neurons from stem cells. Those approaches are powerful, highly technical, and unique in the field of neuroendocrine research. GnRH cell cultures derived from both embryonic olfactory placode and stem cells provide tools to study the mechanism of GnRH pulse-generation, the rapid action of steroid hormones, and epigenetic control of GnRH neuronal maturation. Furthermore, the in vivo measurements of GnRH, neuropeptides and neurotransmitters allows assessment of hypothalamic function under various physiological conditions, including the events across puberty. We have shown that an accelerated increase in body weight impacts the timing of puberty by epigenetic modification of the GnRH neurosecretory system. Current goals are to determine the role of “neuroestradiol” (synthesized locally in the hypothalamus) in regulation of the preovulatory GnRH surge, and to further clarify the developmental changes in the neurocircuitry involved in pubertal increase in GnRH release.