Assistant Dean, Essentials Curriculum
Divisions of Reproductive Sciences
Department of Obstetrics and Gynecology
PhD (1987) University of Newcastle upon Tyne
Research Complex 2
12700 East 19th Avenue
Room 3007, MS 8309
Aurora, CO 80045
Phone: (303) 724-3507
Fax: (303) 724-3512
My research interests focus on hormone/growth factor signaling and cancer. Specifically, our laboratory is studying the role of selective protein kinase C (PKC) isoforms in the modulation of cell growth and death in endometrial cancer. Endometrial cancer is the most common invasive gynecological malignancy in the United States. Although the annual incidence of endometrial cancer has remained relatively constant over the past decade, statistics indicate a dramatic increase in mortality, suggesting a higher prevalence of tumors, which are refractory to treatment. Thus, there is an urgent need to identify prognostic markers in endometrial cancer and to develop agents that have greater efficacy and biological specificity in the treatment of gynecological malignancies.
Recent studies from our laboratory and others suggest that members of the protein kinase C (PKC) family play critical roles in the pathogenesis of endometrial tumors, regulating both proliferation and programmed cell death (apoptosis), Moreover, PKC isozyme expression patterns may reflect the invasive or metastatic potential of endometrial cancers. Using endometrial cancer cell lines and specific adenoviral constructs, we have investigated the role of specific PKCs in etoposide-induced cell cycle arrest and apoptosis. Our results suggest that PKCα and δ exert opposing influences on proliferation and apoptosis in endometrial tumors. PKCα appears to promote proliferation and survival of endometrial cancer cells, whereas PKCδ is pro-apoptotic. Thus, PKCs are clearly important factors in the formation and progression of endometrial tumors. However, little is known regarding the molecular mechanisms underlying PKC modulation of proliferation and apoptosis in the endometrium, particularly with respect to the possible differential role of specific PKC isoforms. We postulate that specific transcriptional, mitogenic and/or apoptotic responses to PKC and isoforms may result in a more aggressive, chemotherapy-resistant endometrial tumor phenotype. Further study of PKCs in the endometrium may identify novel diagnostic/ prognostic indicators and provide new potential targets for therapeutic intervention.
We are also investigating the role of growth factor signaling and Ets transcription factors in the pathogenesis of uterine fibroids or leiomyomata.