Denise C. Connolly, PhD
Office Phone: 215-728-1004
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 only partially understood. Our laboratory is interested in defining molecular mechanisms that contribute to peritoneal dissemination of ovarian cancer cells to identify 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 with the ultimate goal of identifying therapeutic agents that inhibit the spread of ovarian cancer.
To facilitate our studies, we have developed a variety of mouse models of EOC, including 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. Female MISIIR-TAg mice develop spontaneous EOC that share pathological and molecular features with human EOC. We also use human ovarian carcinoma cells line xenograft models, and more recently have begun to develop novel xenograft models from patient-derived tumor tissue. These mouse models, as well as tissues and cell lines developed from them are currently being used to study the mechanisms of EOC tumor progression and metastasis.Description of research projects
- Liu, H.*, Xiao, F.*, Serebriiskii, I.G., O’Brien, S.W., Maglaty, M.A., Astsaturov, I., Martin, L.P., Litwin, S., Proia, D.A., Golemis, E.A. and Connolly, D.C. Network analysis identifies an HSP90-central hub susceptible in ovarian cancer. Clin. Cancer Res. 2013 Jul 30. doi: 10.1158/1078-0432. CCR-13-1115 [Epub ahead of print]. PubMed
*Indicates co-first authorship.
- Do, T.-V., Xiao, F., Bickel, L.E., Klein-Szanto, A.J., Pathak, H.B., Hua, X., Howe, C., O’Brien, S. W., Maglaty, M., Ecsedy, J.A., Golemis, E.A., Schilder, R.J., Godwin, A.K., and Connolly, D.C. Aurora kinase A mediates epithelial ovarian cancer migration and adhesion. Oncogene. 2013 Jan 21. doi: 10.1038/onc.2012.632. [Epub ahead of print]. PubMed
- Hensley, H.H., Roder, N.A., O’Brien, S.W., Bickel, L.E., Xiao, F., Litwin S., and Connolly, D.C. 2012. Combined in vivo molecular and anatomic imaging for detection of ovarian carcinoma-associated protease activity and integrin expression in mice. Neoplasia 14:451-462 , PubMed
- Ratushny, V., Pathak, H.B., Beharry, N. Tikhmyanova, N., Xiao, F., Li, T., Litwin, S. Connolly, D.C., Yen, T.J. Weiner, L.M., Godwin, A.K. and Golemis, E.A. 2012. Dual inhibition of SRC and Aurora kinases induces postmitotic attachment defects and cell death. Oncogene, 31:1217-1227. , PubMed
- Quinn, B.A., Xiao, F, Bickel, L., Marin, L., Hua, X., Klein-Szanto, A. and Connolly, D.C. 2010. Development of a syngeneic mouse model of epithelial ovarian cancer. Journal of Ovarian Research 3:24. , PubMed
- Quinn, B.A., Brake, T., Hua, X., Baxter-Jones, K., Ellenson, L.H., Litwin, S., Connolly, D.C. Induction of ovarian leiomyosarcomas in mice by conditional inactivation of Brca1 and p53. PLoS One 4(12):e8404, 2009. PMID:20046879, PubMed
- Hensley, H., Quinn, B.A., Wolf. R.L., Litwin, S., Mabuchi, S., Williams, S.J., Williams, C., Hamilton, T.C., Connolly, D.C. Magnetic resonance imaging for detection and determination of tumor volume in a genetically engineered mouse model of ovarian cancer. Cancer Biol. Ther. 6:1717-1725, 2007. PubMed
- Connolly, D.C., Bao, R., Nikitin, A.Y., Stephens, K.C., Poole, T., Hua, X., Harris, S.S., Vanderhyden, B.C., Hamilton, T.C. Female mice chimeric for the expression of the SV40 TAg under control of the MISIIR promoter develop epithelial ovarian cancer. Cancer Res. 63:1389-1397, 2003. PubMed