Hugh S. Taylor MD
Anita O'Keeffe Young Professor of Obstetrics, Gynecology, and Reproductive Sciences and Professor of Molecular, Cellular, and Developmental Biology; Chief of Obstetrics and Gynecology, Yale-New Haven Hospital; Anita O'Keeffe Young Professor of Women's Health, Yale University
Endometriosis; Stem Cells; Embryo Implantation; Asherman's Syndrome; Menopause; Uterine Development; Endorcrine Disruption; Developmental Programming
Extensive Research Description
Endometriosis is characterized by the ectopic growth of endometrium outside of the uterus. It is a common and debilitating disease, causing pain or infertility in approximately 10% of reproductive age women. We have identified several novel mechanisms that lead to and regulate this disease. Our group has demonstrated a role for stem cells, epigenetics and micro RNA in this disease. We have also identified several novel markers of endometriosis and therapies to treat the disease.
Endometrial renewal in each menstrual cycle depends on a small pool of tissue-specific stem cells. These endogenous stem cells allow the rapid regeneration of the endometrium necessary to support pregnancy. My laboratory continues to explore the role of adult stem cells from the endometrium and their role in pathophysiology. We were the first to identify an exogenous source of stem cells that contribute to endometrial regeneration. Bone marrow and other tissues contribute stem cells to the circulation that can engraft and repair the uterus; these cells have proven to be useful in the treatment of Asherman’s syndrome in an animal model. Further, some of these cells remain as multipotent stem cells in the uterine endometrium and can be readily obtained in a simple office biopsy. The cells display remarkable plasticity and we have been able to differentiate them into insulin producing cells, neuronal cells, cartilage as well as other cell types. We have used these differentiated cells in regenerative medicine and have demonstrated their effectiveness in animal models of diseases including diabetes and Parkinson’s disease.
The laboratory also studies uterine development. We were the first to describe the molecular mechanism by which the Mullerian duct differentiates into different components of the adult female reproductive track. Differential expression of HOX genes directs segments of the Mullerian duct to take on distinct developmental identities, resulting in the axial differentiation of the fallopian tubes, uterus, cervix and vagina. Perturbation of this process leads to uterine developmental anomalies and infertility. We have examined the role of endocrine disruptors such as bisphenol A (BPA) and diethylstilbestrol (DES) on the developing female reproductive system. These agents and other environmental estrogens disturb the axial patterning of the female reproductive tract altering development and adult reproductive performance. We have demonstrated that this is largely accomplished by epigenetic reprogramming driven by these compounds.
Many of the same genes that are used in uterine development are subsequently used in cyclic endometrial development in adults. We have characterized the role of HOXA10 in endometrial development and receptivity to embryo implantation. This gene is required for fertility and abnormally expressed in several forms of infertility, leading to failed implantation and pregnancy loss.
We also conduct clinical and translational work on the menopause. We have a particular interest in the effects of menopausal hormone therapies on the endometrium.