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Department of Obstetrics, Gynecology & Women's Health

Douglas D. Taylor, PhD

Dr. Douglas Taylor’s research activities are directed at studies that characterize the interaction between the immune system and components of the female reproductive system. These interactions can define pregnancy success or complications, infertility, and the development of gynecologic cancers over a woman’s lifespan. The lab’s research focuses on three main areas of research:

1. Immunology of pregnancy: Studies are designed to understand immunological factors controlling the normal development of the trophoblast and its interaction with immune cells present at the maternal-fetal interface. The release of placental exosomes into the maternal circulation appears to play a critical role in second and third trimester regulation of maternal anti-fetal immune responses; however, aberrations the exosomal pathways appear to be key determinants of preterm birth, preeclampsia, and intrauterine growth restriction.
2. Immunology of infertility: Studies are designed to understand immunologic alterations linked with specific etiologies leading to a diagnosis of infertility: premature ovarian failure, polycystic ovarian syndrome, and endometriosis. Infertile women commonly exhibit autoantibodies and their infertility also correlates with the presence of autoimmune diseases. These autoantibodies exhibit distinct target recognition based on their etiologies. Thus, identification of their target antigen recognition patterns can serve as diagnostic markers of specific infertilities.
3. Tumor Immunology: Studies are designed to understand the interaction between cancer cells and immune cells. A major focus is to understand immune modulation mediated by tumor-derived exosomes. Tumor exosomes can induce a shift to a predominantly Th2 response leading to the escape of tumors from immune surveillance. Our studies have utilized the shift to an antibody-mediated Th2 response to develop a diagnostic platform for the early detection of gynecologic cancers, based on autologous serologic typing.

Cicek Gercel-Taylor, PhD

Dr. Gercel-Taylor’s research is directed at investigations that define genetic and epigenetic alterations associated with the development of cancer and how these alterations can be modified by hormones and phytohormones as therapeutic agents alone and in combination with conventional therapies. Her lab’s research focuses on four interrelated areas that evolve around the theme of amplifying the efficacy of therapeutic approaches to cancer and chronic diseases associated with aging in women.

1. Prognostic indicators in ovarian cancer. Studies are directed at the identification of prognostic indicators to design and monitor therapy, allowing individualization of therapy. This approach facilitates the identification of therapeutic targets and defines mechanisms regulating drug sensitivity and resistance. The incorporation of molecular markers into the pathologic analysis of ovarian cancer will lead to more appropriate use of drugs, reduced morbidity and optimized efficacy.
2. Cellular response to chemotherapy. Studies are directed to understanding the genetic and epigenetic mechanisms of drug resistance. Use of translational objectives will provide a molecular rationale to guide the choice of therapy and the duration of treatment for individual patients, while defining mechanisms underlying drug resistance will lead to creative approaches for new drug discovery and improved utilization of existing chemotherapies.
3. Hormone therapy in cardiovascular disease (CVD) and cancer. Studies are directed to determining the mechanism through which combination hormone therapy and its individual components can alter the incidence or recurrence of breast and ovarian cancer, as well as the development of CVD. Differential expression of cellular estrogen receptors (ERα, ERβ and GPR30) have been implicated as key determinants in the cellular responses to exogenous estrogens, which can trigger molecular events leading to chronic diseases.
4. Complementary and Alternative medical (CAM) approaches to women’s health. Studies are directed at preclinical and translational studies of CAM approaches to secondary prevention and management of atherosclerosis. In addition to the direct consequences on vascular endothelial cells, CAMs may enhance or inhibit immune responses, including inflammation. Elucidating the underlying mechanisms of CAM therapies will identify key endpoints and strengthen the design of CAM clinical applications.

Zhenmin Lei, MD, PhD

My laboratory is set up to conduct molecular biological experiments using a variety of techniques that involve transgenic, gene knockout, biochemistry, and cell biology. Our work involves the combination of these in vivo and in vitro approaches to determine the mechanisms of endocrine regulation of reproductive organs and gamete development and differentiation, to elucidate the pathophysiology of female and male infertility, to clarify complications of pregnancy, birth defects and aging, and to develop better diagnoses and treatments for these disorders. My current research focus includes the following:

1. To determine the molecular mechanism by which gonadotropins control folliculogenesis and spermatogenesis. Using targeted gene disruption technology, we have successively established LH receptor (LHR) knockout (LHRKO) and double FSH/LHR knockout (FSH/LHRKO) mouse models. These animal models provide us a unique opportunity to dissect the molecular mechanisms by which gonadotropins control folliculogenesis and spermatogenesis, to identify gonadotropin-dependent genes in gonads that are critical for gamete development and differentiation, and to distinguish the role of gonadotropins and sex steroid hormones as well as to differentiate the role of LH and FSH.
2. To determine the mechanism of androgen-dependent inguinoscrotal testicular descent Cryptorchidism, the failure of testes to descend into the scrotum, is a very common birth defect in males. The mechanism that regulates the inguinoscrotal phase is not completely understood, even though the incidence of this defect is commonly seen clinically. Genetic removal of LH receptors in males has exhibited a bilateral cryptorchid phenotype resulting from an arrestment in the stage of inguinoscrotal testis descent, which can be completed by postnatal testosterone replacement therapy. We are currently working on this animal model to determine the signal transduction mechanism and related genes that are critical in controlling inguinoscrotal testicular descent into the scrotum which is induced by androgen.
3. LH and cognitive functions in postmenopausal women and the relevance to Alzheimer's disease The effect of estrogens on protection against Alzheimer’s disease (AD) has been challenged by recent clinical trials that indicated estrogen replacement therapy increases the incidence of dementia in aging women. Several lines of circumstantial evidence indicate that chronically elevated LH levels during reproductive aging act on the brain LHR and contribute to the pathogenesis of AD. We are currently testing this hypothesis by creating a biogenic animal model which over-expresses a mutant amyloid precursor protein that is unambiguously known to associate with AD in LHRKO mice. We are evaluating the effect of lack of LHR in the brain on amyloid-beta deposition, neurological circuit relevant molecules, and cognitive activities. This project will provide crucial insight into the relationship between LH and AD, which may lead to novel preventive and therapeutic strategies for the disease, such as manipulation of age-related increase in LH levels or LH action in the aging brain.
4. Androgen dysregulation in gestational diabetes mellitus (GDM) Our preliminary data demonstrate that GDM patients have higher circulating androgens compared to healthy controls and that there is a strong correlation between insulin and testosterone. The current study is designed to determine the effect of androgen dysregulation on placental development and function which may eventually increase the frequency of maternal and fetal complications associated with GDM as well as the risk of diabetes developing in the offspring.
5. The role of gonadal steroid hormones in pelvic organ prolapse Pelvic organ prolapse (POP) is a common disorder that negatively affects women’s quality of life. The etiology of this distressing condition remains largely unclear. It is known that POP is most frequently seen in the postmenopausal woman, suggesting that a disturbance of gonadal steroid hormones may contribute to the abnormality of the connective tissue in the pelvic cavity. The project is designed to determine aberrant expression of adhesion and connective tissue remodeling molecules that lead to the development of POP and correlate with the changes in sex steroid hormone concentrations and their receptor levels in POP patients. Understanding the relationship of gonadal steroid hormones and POP and the molecular mechanism responsible for the maintenance of the pelvic organ support structures will greatly contribute to the prevention and treatment of POP.