Research Associate Professor
Department of Anatomy and Cell Biology
Ph.D.: 1989, University of Kansas Medical Center
Postdoctoral: University of Kansas Medical Center
Ovarian cancer is the most frequent cause of death from gynecologic malignancies. Although advances have been made in treatment strategies, little change in the survival rate has occurred. One series of studies is aimed at understanding the biology of ovarian cancer and in that understanding, test novel methods for treatment. The objectives of these studies are to establish an adenoviral system of in situ gene transfer using a novel syngeneic mouse model of ovarian cancer and to assess the effects of inhibition of cellular Src kinase activity on progression of the disease. In addition, effects of combined adenoviral-mediated inhibition of tumor Src activity with taxol and cisplatin treatment on the progression of the cancer in the mouse is investigated. In collaboration with medicinal chemists it is our intent to use this model for the discovery of new drugs and drug combinations specific for killing ovarian cancer cells with high and low levels of Src expression.
The peak incidence of ovarian cancer is coincident with menopause and this epidemiological data has lead to the hypothesis that senescence of the female reproductive tract plays a role in the progression of ovarian cancer. Menopause results when the supply of ova in the ovaries is exhausted. Follicle development, and thus production of the ovarian steroids estradiol and progesterone, stops. Hormonal feedback mechanisms then trigger elevated secretion of pituitary gonadotropins. Thus, at the time of menopause in women, when the incidence of ovarian cancer is greatest, multiple hormonal changes occur, including decreased ovarian steroids and increased pituitary gonadotropins. In addition to reproductive senescence, age associated immunosenescence also occurs. Thus, the progression of ovarian cancer around the time of menopause likely may result from both reproductive and immune factors. Studies in the laboratory utilize the mouse model to determine the impact of the age-associated changes in ovarian hormones, pituitary hormones, and immune factors on progression of the disease.
Ovarian follicular development and rupture occur as a result of coordination of several different cell types and functions. The specific roles of each cellular compartment involved in successful ovulation are still under investigation. Studies in the lab assessing follicle development and ovulation make use of a novel model of altered follicle development and blockade of ovulation. Immature hypophysectomized rats treated with a single dose of TCDD (2,3,7,8-tetrachlordibenzo-p-dioxin) followed by standard regimens of gonadotropins (PMSG and hCG) fail to ovulate. The use of TCDD is of particular interest for several reasons. TCDD is a toxicant present in our environment and therefore has the potential to impact multiple aspects of human biology, including reproduction. In addition, TCDD is a compound with estrogenic action. Estrogens are hormones produced by growing ovarian follicles and precise actions of estrogens are critical for successful follicle development and ovulation. Thus, TCDD likely disrupts normal estrogenic actions in the ovary. Our studies assess the impact of TCDD on specific gene expression during follicle development and ovulation.