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My research focuses on the ovarian cancer microenvironment, understanding and targeting the cancer supporting stromal tissues which are critical to the survival, growth and spread of ovarian cancer. Specifically, I study a critical non-malignant component of the ovarian cancer microenvironment, the carcinoma-associated mesenchymal stem cell (CA-MSC). CA-MSCs are stromal progenitor cells which significantly increase tumor growth. I demonstrated that CA-MSCs form a critical BMP4:hedgehog signaling loop with ovarian cancer cells. Blocking this loop with a hedgehog inhibitor prevents CA-MSC mediated tumor growth, enhancement of cancer stem cell-like cells, and chemotherapy resistance. Indeed, the combination of a hedgehog inhibitor and cisplatin not only decreased growth in naïve tumors but led to regression of well established, chemotherapy resistant tumors in a mouse model. This work provides important information regarding tumor:stromal signaling within the ovarian cancer microenvironment, describes a mechanism for the pro-tumorigenic function of CA-MSCs and potentially presents a novel therapeutic approach.
I am also investigating the role of the tumor microenvironment in ovarian cancer metastasis. New evidence demonstrates high grade serous ovarian cancer, the most common and deadly form of ovarian cancer, likely arises in the fallopian tube and the ovary is a critical initial site of metastasis. I developed three novel mouse models of ovarian cancer metastasis which demonstrate ovarian cancer is capable of hematogenous spread with a unique tropism for the ovary. Further, initial metastasis to the ovary appears to be critical for the development of intra-abdominal metastasis implicating unique aspects of the ovary microenvironment in propagating metastasis.
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