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The overall goal of our research is to discover ways to improve the treatment of epithelial ovarian cancer (EOC). Most cases of EOC are diagnosed at advanced stage when disease has spread beyond the ovary. From a clinical standpoint, EOC metastases and ascites production are perhaps the most significant cause of morbidity and mortality in patients because they can affect multiple vital organs in the abdominal cavity. At present, the cellular mechanisms regulating EOC metastasis remain poorly understood. Our laboratory is interested in defining the precise molecular mechanisms of peritoneal dissemination of ovarian cancer cells to identify specific molecular targets for therapeutic intervention in patients. Using a combination of in vitro and in vivo approaches, we hope to better understand EOC tumor biology at the cellular level as well as disease development and progression in animals. Several projects in our laboratory are focused on the cellular pathways involved in ovarian cancer cell migration, attachment and invasion. Specifically, we are interested in the understanding the role of focal adhesion signaling in EOC migration and invasion with the ultimate goal of identifying therapeutic agents that inhibit the spread of ovarian cancer.

To facilitate our studies, we have developed immunocompetent mouse models of EOC. We developed the first transgenic model of spontaneous EOC by expressing the SV40 TAg under transcriptional control of the Müllerian inhibiting substance type II receptor (MISIIR) gene promoter. One transgenic line of MISIIR-Tag mice develop spontaneous EOC with pathological features of serous EOC. Like human EOC, female with significant tumor burden exhibit no symptoms of illness, disease dissemination is typically restricted to the peritoneum and tumor cells share many molecular features with human tumors. We have also isolated a transgenic line of mice that express the transgene at low levels, but do not develop ovarian tumors. These mice can serve as syngeneic recipients for orthotopic implantation of murine ovarian carcinoma (MOVCAR) cells isolated from MISIIR-Tag mice. These transgenic mice, as well as tissues and cell lines developed from them are currently being utilized in conjunction with established human ovarian carcinoma cell lines to study the mechanisms of EOC tumor progression and metastasis.

1. Liang S, Yang N, Pan Y, Deng S, Lin X, Katsaros KF, Hamilton TC, Connolly DC, Coukos G, Zhang L. Expression of activated PIK3CA in ovarian surface epithelium results in hyperplasia but not tumor formation. PLoS ONE 4(1):e4295. Epub 2009 Jan 27. PubMed
2. Choi YS, Hoory T, Monie A, Wu A, Connolly D, Hung, C-F. α-Galactosylceramide enhances the protective and therapeutic effects of tumor cell based vaccines for ovarian tumors. Vaccine. 2008;26(46):5855-5863. PubMed
3. Melikechi N, Ding H, Rock S, Marcano OA, Connolly D. Laser-induced breakdown spectroscopy of whole blood and other liquid organic compounds. In: Optical Diagnostic and Sensing VIII (Cote G, Priezzhev AV, eds.). Proceeding of SPIE 6863, 68630O1-7, 2008;DOI: 10.1117/12.761901.
4. Melikechi N, Ding H, Marcano OA, Rock S, Connolly D. Laser-induced breakdown spectroscopy of alcohols and proteins solutions. AIP Proceedings: Atomic, Molecular, and Optical Physics. 2008;992:1177-1182.
5. Hensley H, Quinn BA, Wolf RL, Litwin S, Mabuchi S, Williams SJ, Williams C, Hamilton TC, Connolly DC. Magnetic resonance imaging for detection and determination of tumor volume in a genetically engineered mouse model of ovarian cancer. Cancer Biol Ther. 2007;6:1717-1725. PubMed
6. Mabuchi S, Altomare DA, Connolly DC, Klein Szanto A, Litwin S, Hoelzle MK, Hensley HH, Hamilton TC, Testa JR. RAD001 delays tumor onset and progression in a transgenic mouse model of ovarian cancer. Cancer Res. 2007;67:2408-2413. PubMed
7. Pieretti-Vanmarcke R, Donahoe PK, Pearsall L, Connolly DC, Dinulescu DM, Halpern EF, Seiden MV, McLaughlin DT. MIS enhances subclinical doses of chemotherapeutic agents to inhibit human and mouse ovarian cancer. Proc Natl Acad Sci USA. 2006;103:17426-17431. PubMed
8. Connolly DC, Bao R, Nikitin AY, Stephens KC, Poole T, Hua X, Harris SS, Vanderhyden BC, Hamilton TC. Female mice chimeric for the expression of the SV40 TAg under control of the MISIIR promoter develop epithelial ovarian cancer. Cancer Res. 2003;63:1389-1397. PubMed