Laboratory Research – Reproductive Biology
The Laboratory of Reproductive Biology in the department of Obstetrics and Gynecology at BUMC conducts research on immunology, sexually transmitted infections, and their effects on fertility. Current projects include: defining mechanisms of cell-associated HIV-1 transmission, characterizing genital tract innate immune defense, and studies on HIV replication and drug resistance in the genital tract compartment.
This basic research provides a foundation for the development of microbicides and vaccines to prevent the sexual transmission of HIV-1 and other pathogens. The laboratory also conducts translational research, and enjoys collaborating with clinicians, residents and students on clinically-oriented projects. We have conducted collaborative research on a wide range of clinical topics such as immunological mechanisms of recurrent miscarriage, preeclampsia and infertility, and have pioneered several clinical protocols including:
THE MOLECULAR BASIS OF ESTROGEN-DEPENDENT DISORDERS
Estrogen-dependent gynecological disease, such as breast and endometrial cancer and endometriosis, rarely arise in women who have been castrated at an early age and who have not received hormone replacement. Patients status post oophorectomy who develop these disorders many years later may harbor gain-of-function mutations resulting in overproduction of estrogen. We plan to identify patients who have developed severe estrogen-dependent disorders despite presumed estrogen deficiency to order to screen for mutations. These "experiments of nature" may enable us to identify genes already implicated in disorders of estrogen excess (e.g. aromatase, estrogen receptor alpha), identify new genes involved in these disorders, and establish genotype-phenotype correlations for the genetic defects discovered.
Transsexual female-to male patients are treated with high dose testosterone during the process of gender reassignment. The effects of testosterone at these doses are incompletely studied, including the effects on the female genital tract. In current gynecologic practice, it is recommended that transsexual female to male patients receiving high dose testosterone undergo removal of the uterus due to concerns about the risk of endometrial cancer. This recommendation is not supported by data and is based only on observational models from over 20 years ago. No study has looked closely at endometrial changes caused by testosterone in these patients to justify the practice of hysterectomy solely for cancer prevention. In our project, we intend to examine archival surgical pathology specimens from a specific population of female-to-male trassexual patients who were exposed to testosterone prior to hysterectomy, using immunohistochemistry or real-time PCR to quantify oncogene expression in endometrial cells and evidence of early tumor formation.