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. 
Combined FMT and MRI of ovarian tumors in mice.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. To facilitate our studies, we have developed a variety of transgenic and novel patient-derived mouse models of EOC. 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.
Gabbasov R, Xiao F, Howe CG, Bickel LE, O'Brien SW, Benrubi D, Do TV, Zhou Y, Nicolas E, Cai KQ, Litwin S, Seo S, Golemis EA, Connolly DC. NEDD9 promotes oncogenic signaling, a stem/mesenchymal gene signature, and aggressive ovarian cancer growth in mice. Oncogene, 2018. PubMed
Tyner J.W., Tognon C.E., Bottomly D., Wilmot B., Kurtz S.E., Savage S.L., Long N., Schultz A.R., Traer E., Abel M., Agarwal A., Blucher A., Borate U., Bryant J., Burke R., Carlos A., Carpenter R., Carroll J., Chang B.H., Coblentz C., d'Almeida A., Cook R., Danilov A., Dao K.T., Degnin M., Devine D., Dibb J., Edwards D.K.t., Eide C.A., English I., Glover J., Henson R., Ho H., Jemal A., Johnson K., Johnson R., Junio B., Kaempf A., Leonard J., Lin C., Liu S.Q., Lo P., Loriaux M.M., Luty S., Macey T., MacManiman J., Martinez J., Mori M., Nelson D., Nichols C., Peters J., Ramsdill J., Rofelty A., Schuff R., Searles R., Segerdell E., Smith R.L., Spurgeon S.E., Sweeney T., Thapa A., Visser C., Wagner J., Watanabe-Smith K., Werth K., Wolf J., White L., Yates A., Zhang H., Cogle C.R., Collins R.H., Connolly D.C., Deininger M.W., Drusbosky L., Hourigan C.S., Jordan C.T., Kropf P., Lin T.L., Martinez M.E., Medeiros B.C., Pallapati R.R., Pollyea D.A., Swords R.T., Watts J.M., Weir S.J., Wiest D.L., Winters R.M., McWeeney S.K., Druker B.J., Functional genomic landscape of acute myeloid leukaemia. Nature. 562(7728): 526-531, 2018. PMC6280667. 43.070
Perales-Puchalt A., Svoronos N., Rutkowski M.R., Allegrezza M.J., Tesone A.J., Payne K.K., Wickramasinghe J., Nguyen J.M., O'Brien S.W., Gumireddy K., Huang Q., Cadungog M.G., Connolly D.C., Tchou J., Curiel T.J., Conejo-Garcia J.R., Follicle-stimulating hormone receptor is expressed by most ovarian cancer subtypes and is a safe and effective immunotherapeutic target. Clin Cancer Res. 23(2): 441-453, 2017. PMC5241180. 8.911
Gritsina G, Xiao F, O'Brien SW, Gabbasov R, Maglaty MA, Xu RH, Thapa RJ, Zhou Y, Nicolas E, Litwin S, Balachandran S, Sigal LJ, Huszar D, Connolly DC. Targeted Blockade of JAK/STAT3 Signaling Inhibits Ovarian Carcinoma Growth. Mol Cancer Ther 2015;14:1035-47. PubMed
Liu H, Xiao F, Serebriiskii IG, O'Brien SW, Maglaty MA, Astsaturov I, Litwin S, Martin LP, Proia DA, Golemis EA, Connolly DC. Network Analysis Identifies an HSP90-Central Hub Susceptible in Ovarian Cancer. Clinical Cancer Research 2013;Published OnlineFirst July 30, 2013; doi:10.1158/1078-0432. CCR-13-1115.abstract. PubMed
Do TV, Xiao F, Bickel LE, Klein-Szanto AJ, Pathak HB, Hua X, Howe C, O'Brien SW, Maglaty M, Ecsedy JA, Litwin S, Golemis EA, Schilder RJ, Godwin AK, Connolly DC. Aurora kinase A mediates epithelial ovarian cancer cell migration and adhesion. Oncogene 2014;33:539-49. PubMed
Hensley HH, Roder NA, O'Brien SW, Bickel LE, Xiao F, Litwin S, Connolly DC. Combined in vivo molecular and anatomic imaging for detection of ovarian carcinoma-associated protease activity and integrin expression in mice. Neoplasia 2012;14:451-62. PubMed
Quinn BA, Xiao F, Bickel L, Martin L, Hua X, Klein-Szanto A, Connolly DC. Development of a syngeneic mouse model of epithelial ovarian cancer. J Ovarian Res 2010;3:24. PubMed
Quinn BA, Brake T, Hua X, Baxter-Jones K, Litwin S, Ellenson LH, Connolly DC. Induction of ovarian leiomyosarcomas in mice by conditional inactivation of Brca1 and p53. PLoS One 2009;4:e8404. PubMed
Connolly DC, Hensley HH. Xenograft and Transgenic Mouse Models of Epithelial Ovarian Cancer and Non Invasive Imaging Modalities to Monitor Ovarian Tumor Growth In situ -Applications in Evaluating Novel Therapeutic Agents. Curr Protoc Pharmacol 2009;45:14 2 1- 2 26. PubMed
Hensley H, Quinn BA, Wolf RL, Litwin SL, 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. PubMed
Connolly DC, Bao, R., Nikitin, A.Y., Stephens, K.C., Poole, T.W., Hua, X., Harris, S.S., Vanderhyden, B.C., Hamilton, T.C. Female mice chimeric for expression of the SV40 TAg under control of the MISIIR promoter develop epithelial ovarian cancer. Cancer Research 2003;63:1389-97.
Denise.Connolly@fccc.edu
Office Phone: 215-728-1004
215-728-2741
Office: W 310
Denise.Connolly@fccc.edu
Office Phone: 215-728-1004
215-728-2741
Office: W 310
Associate Professor
Director, Biosample Repository Facility
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. Combined FMT and MRI of ovarian tumors in mice.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. To facilitate our studies, we have developed a variety of transgenic and novel patient-derived mouse models of EOC. 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.
Gabbasov R, Xiao F, Howe CG, Bickel LE, O'Brien SW, Benrubi D, Do TV, Zhou Y, Nicolas E, Cai KQ, Litwin S, Seo S, Golemis EA, Connolly DC. NEDD9 promotes oncogenic signaling, a stem/mesenchymal gene signature, and aggressive ovarian cancer growth in mice. Oncogene, 2018. PubMed
Tyner J.W., Tognon C.E., Bottomly D., Wilmot B., Kurtz S.E., Savage S.L., Long N., Schultz A.R., Traer E., Abel M., Agarwal A., Blucher A., Borate U., Bryant J., Burke R., Carlos A., Carpenter R., Carroll J., Chang B.H., Coblentz C., d'Almeida A., Cook R., Danilov A., Dao K.T., Degnin M., Devine D., Dibb J., Edwards D.K.t., Eide C.A., English I., Glover J., Henson R., Ho H., Jemal A., Johnson K., Johnson R., Junio B., Kaempf A., Leonard J., Lin C., Liu S.Q., Lo P., Loriaux M.M., Luty S., Macey T., MacManiman J., Martinez J., Mori M., Nelson D., Nichols C., Peters J., Ramsdill J., Rofelty A., Schuff R., Searles R., Segerdell E., Smith R.L., Spurgeon S.E., Sweeney T., Thapa A., Visser C., Wagner J., Watanabe-Smith K., Werth K., Wolf J., White L., Yates A., Zhang H., Cogle C.R., Collins R.H., Connolly D.C., Deininger M.W., Drusbosky L., Hourigan C.S., Jordan C.T., Kropf P., Lin T.L., Martinez M.E., Medeiros B.C., Pallapati R.R., Pollyea D.A., Swords R.T., Watts J.M., Weir S.J., Wiest D.L., Winters R.M., McWeeney S.K., Druker B.J., Functional genomic landscape of acute myeloid leukaemia. Nature. 562(7728): 526-531, 2018. PMC6280667. 43.070
Perales-Puchalt A., Svoronos N., Rutkowski M.R., Allegrezza M.J., Tesone A.J., Payne K.K., Wickramasinghe J., Nguyen J.M., O'Brien S.W., Gumireddy K., Huang Q., Cadungog M.G., Connolly D.C., Tchou J., Curiel T.J., Conejo-Garcia J.R., Follicle-stimulating hormone receptor is expressed by most ovarian cancer subtypes and is a safe and effective immunotherapeutic target. Clin Cancer Res. 23(2): 441-453, 2017. PMC5241180. 8.911
Gritsina G, Xiao F, O'Brien SW, Gabbasov R, Maglaty MA, Xu RH, Thapa RJ, Zhou Y, Nicolas E, Litwin S, Balachandran S, Sigal LJ, Huszar D, Connolly DC. Targeted Blockade of JAK/STAT3 Signaling Inhibits Ovarian Carcinoma Growth. Mol Cancer Ther 2015;14:1035-47. PubMed
Liu H, Xiao F, Serebriiskii IG, O'Brien SW, Maglaty MA, Astsaturov I, Litwin S, Martin LP, Proia DA, Golemis EA, Connolly DC. Network Analysis Identifies an HSP90-Central Hub Susceptible in Ovarian Cancer. Clinical Cancer Research 2013;Published OnlineFirst July 30, 2013; doi:10.1158/1078-0432. CCR-13-1115.abstract. PubMed
Do TV, Xiao F, Bickel LE, Klein-Szanto AJ, Pathak HB, Hua X, Howe C, O'Brien SW, Maglaty M, Ecsedy JA, Litwin S, Golemis EA, Schilder RJ, Godwin AK, Connolly DC. Aurora kinase A mediates epithelial ovarian cancer cell migration and adhesion. Oncogene 2014;33:539-49. PubMed
Hensley HH, Roder NA, O'Brien SW, Bickel LE, Xiao F, Litwin S, Connolly DC. Combined in vivo molecular and anatomic imaging for detection of ovarian carcinoma-associated protease activity and integrin expression in mice. Neoplasia 2012;14:451-62. PubMed
Quinn BA, Xiao F, Bickel L, Martin L, Hua X, Klein-Szanto A, Connolly DC. Development of a syngeneic mouse model of epithelial ovarian cancer. J Ovarian Res 2010;3:24. PubMed
Quinn BA, Brake T, Hua X, Baxter-Jones K, Litwin S, Ellenson LH, Connolly DC. Induction of ovarian leiomyosarcomas in mice by conditional inactivation of Brca1 and p53. PLoS One 2009;4:e8404. PubMed
Connolly DC, Hensley HH. Xenograft and Transgenic Mouse Models of Epithelial Ovarian Cancer and Non Invasive Imaging Modalities to Monitor Ovarian Tumor Growth In situ -Applications in Evaluating Novel Therapeutic Agents. Curr Protoc Pharmacol 2009;45:14 2 1- 2 26. PubMed
Hensley H, Quinn BA, Wolf RL, Litwin SL, 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. PubMed
Connolly DC, Bao, R., Nikitin, A.Y., Stephens, K.C., Poole, T.W., Hua, X., Harris, S.S., Vanderhyden, B.C., Hamilton, T.C. Female mice chimeric for expression of the SV40 TAg under control of the MISIIR promoter develop epithelial ovarian cancer. Cancer Research 2003;63:1389-97.
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