• Current Projects

    Characterization of nongenomic uterine actions of natural estrogen and xenoestrogens without involving the nuclear ERa and ERb.

    For more than 60 years, scientists have recognized “early” and “late” phase uterine responses to estrogen, though the mechanisms behind these changing responses remain unclear. Researchers commonly assume that estrogenic responses depend on interaction with one of two estrogen receptors (ER-alpha or ER-beta).

    Research that involved the injection of estrogenic ligands in mice null for ERa (or in which ER activity has been silenced by antiestrogens) suggests that estrogenic compounds can affect the regulation of uterine genes that are not mediated by ER-dependent mechanisms. We have identified several downstream target genes regulated early in the uterus by estrogens via a nonclassical pathway.

    The primary goal of our current research is to demonstrate that early estrogen-responsive nonclassical genes cooperate with late-responsive actions via ERa, producing a full complement of estrogenic growth response in the uterus.

    Aspects of uterine cell cycle regulation of decidualization in implantation.

    Uterine stromal cell decidualization is critical to the success of embryo implantation and subsequent pregnancy. The decidualization process is characterized by stromal cell proliferation and differentiation into a specialized type of cells (decidual cells) with the acquisition of polyploidy. The onset of this transformation is believed to occur in a tightly regulated manner in the cell cycle at two particular checkpoints: G1-S and G2-M. Our earlier research showed that cyclin D3 (a G1 phase cell cyclin) is associated with the onset of decidualization in the mouse uterus. The objective of this research is to define, in mouse models, the cycle regulatory mechanisms associated with decidualization and polyploidization in embryo implantation.

  • A model for canonical WNT signaling in the regulation of E2-dependent uterine growth.

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  • Model for stromal cell decidualization and polyploidy.

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