As part of the Ovarian Epithelial Cancer Pathobiology program in the Department of Pathology at USF, the research focus in my lab is on early molecular changes responsible for ovarian epithelial transformation. In particular, we are interested in the molecular regulation of telomerase, DNA repair and apoptosis associated with a familial risk for ovarian cancer. Our research concerns the signal transduction pathways involved in early stages of ovarian oncogenesis. We are examining the molecular mechanism(s) that regulate telomerase, a ribonucleoprotein expressed in over 90% of all cancers. Studies in this laboratory also indicate that telomerase re-expression appears to confer increased cancer cell survival and resistance to chemotherapeutic-mediated apoptosis associated with elevated levels of anti-apopototic proteins including survivin and Bcl-2. Consequently, a recent translational study revealed Bcl-2 present at levels 10x greater in urine samples from women with ovarian cancer compared to normal controls or women with benign gynecologic disease. Lastly, in agreement with clinical reports that certain women with hereditary ovarian cancer initially respond better to chemotherapy, other studies in this laboratory are directed at understanding the molecular mechanism(s) by which BRCA1 amino-terminal mutations result in enhanced cellular apoptosis following genotoxic stress. Thus, while elevated urinary levels of Bcl-2 may provide a novel, safe, sensitive and economic method ovarian cancer detection, inhibition of the signaling pathways regulating telomerase activity or activation of cellular BRCA1 amino-terminal mutation targets may be beneficial for the treatment of ovarian cancer, an insipid disease with the highest mortality of all gynecological cancers.