Research Project: UTX: A Novel Regulator of Decidualization?
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- Ivanov, Ivan
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During pregnancy, endometrial stromal cells transdifferentiate into decidual cells, a process known as decidualization, to support the implanting embryos. The development of decidua with full functionality requires coordinated cell proliferation, differentiation, and apoptosis. Despite a series of elegant studies that have made breakthroughs in progesterone receptor signaling, transcription factors, and growth factor signaling in uterine decidualization, the role of epigenetic regulators remains poorly defined. Defective decidualization leads to pregnancy complications such as miscarriage, intrauterine growth restriction, and pregnancy loss. Therefore, identification of molecular mechanisms underpinning decidualization is of fundamental importance. Built on novel preliminary findings using conditional knockout mouse model of UTX in the uterus, this proposal will identify the function of a lysine demethylase, UTX, in the development of an integral decidua and decipher how UTX regulates endometrial stromal cell differentiation. A multipronged approach incorporating genetic, cellular, and molecular tools has been proposed. The findings are anticipated to establish a new paradigm in understanding the role of epigenetic regulators in uterine biology. Thus, completion of the proposed studies will have a substantial impact, with potential translational implications in the treatment of endometrial dysfunction and pregnancy loss associated with decidualization defects.
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