Our laboratory, using a systems biology approach, investigates molecular mechanisms underlying: normal and abnormal human endometrial development and function; the human female reproductive tract as a portal of entry for infection; and the exploration of endometrial renewal through stem cell-focused research.
Human endometrium is a steroid hormone responsive tissue in which embryo implantation occurs, or in non-conception cycles is shed and regenerated. It is also a mucosal tissue providing immune surveillance and protection against infectious agents ascending to the upper reproductive tract and systemically. Abnormalities of the endometrium can result in abnormal bleeding, poor regenerative capacity, endometriosis, infertility, implantation disorders (miscarriage, pre-eclampsia, intrauterine fetal growth restriction, pre-term birth), infection, polyps, hyperplasia, and cancer.
Human Endometrium as a Target of Steroid Hormones and Relevance to Health and Disease.
We use whole tissue and in vitro models of human endometrial primary cells to investigate the roles of steroid hormones, IGFs, WNT family members, and epigenetics in endometrial cellular proliferation and differentiation. We have also pursued gene discovery in normal endometrium across the menstrual cycle, in the disorder of endometriosis, in women with HIV, and in women using contraceptive steroids, contraceptive gels and excipients. These studies have resulted in identification of basic biologic processes within the tissue in response to steroid hormones normally and in several disease states and therapies, signaling pathways, and biomarkers of disease and novel therapeutic targets.
Endometrial Stem/Progenitor Cells
The endometrium is a tissue that has potent regenerative properties, capable of shedding each month during menses and subsequently regenerating without scarring. We are interested in identifying populations of mesenchymal, endothelial and epithelial stem cell progenitors responsible for this cyclic regeneration, with the goal of utilizing these cells for therapeutic purposes.
The Human Female Reproductive Tract as a Portal of Entry for Infection
We have pursued a metagenomics approach to defining bacterial flora in human vagina under different steroid hormone conditions and in the setting of preterm delivery. Furthermore, we are investigating the role of the endometrium as a portal of entry for male-to-female HIV-1 transmission. We also participate in an NIH clinical trial group on therapies and prevention of sexually transmitted infections in women and men.
Immune Activation, Inflammation and the Endometrium
Currently, we are exploring the effects of common pelvic, uterine, and systemic disorders on endometrial function, including endometriosis, polycystic ovary syndrome (PCOS), and uterine fibroids. Emerging studies indicate that endometrial cells from women with these disorders exhibit biomarkers associated with inflammation and immune cell recruitment, which may contribute to pathological conditions such as uterine bleeding, pelvic pain, and infertility. To date, we have identified biomarkers of endometriosis using multidimensional genomic data.
The UCSF NIH Human Endometrial Tissue and DNA Bank
The Endometrial Tissue bank was established by Dr. Giudice in 1999 and is a national repository and resource for endometrial/blood specimens. For more information, visit the UCSF NIH Human Endometrial Tissue and DNA Bank.