We are interested in the role of HOX gene expression in reproductive biology. HOX genes are necessary for the normal differentiation of the female reproductive tract. During embryogenesis these genes assign positional identity to segments of the Müllerian duct, determining which adult structure will form at each point along this undifferentiated axis. We have shown that sex steroids regulate HOX genes and that endocrine disruptors alter expression of HOX genes. Endocrine disruption by DES and other xenoestrogens leads to uterine anomalies, at least in part, by disturbing the normal pattern of HOX gene expression.
In the adult endometrium of humans and other mammals, HOXA10 is expressed in a menstrual cycle dependent fashion, where it regulates endometrial receptivity to embryo implantation. Alteration of HOXA10 can effect endometrial receptivity in animals models; similarly, women with low implantation rates often have diminshed or acyclic HOXA10 expression. We are identifying the factors that regulate HOXA10 in this tissue and downstream targets of this transcription factor. Additionally we have identified extra-uterine sources of endometrial stem cells. We are characterizing their contribution to endometrium and the molecular pathways that lead to endometrial cell identity.
Endometriosis is the ectpoic growth of endometrium. This tissue also expresses HOX genes. Women with this condition also show abnormal gene expression in their eutopic endometrum. We are studying the genes involved in regulation of endometriosis as well as its effect on endometrium. We are also exploring the possibility that endometriosis can arise from ectopic differentiation of circulating stem cells.
Finally, clinical research in our laboratory is also focused on menopause and perimenopause. We are interested on the effects of hormone therapy on the heart, bone, skin, brain, uterus, and breast. This includes participation in the KEEPS trial as well as several Yale centered clinical trials.