Translational Ovarian Cancer Research Program

Translational Ovarian Cancer Research Program
Ovarian cancer is the most lethal of the gynaecological cancers, yet over the last decade very little progress has been made to improve the overall survival of women with this disease. To try to buck this current trend, we at the LRCP are using an integrated, multidisciplinary team approach to quickly develop focused, clinically-relevant research endeavours.

ID genes in ovarian cancer

The Inhibitors of DNA-binding (ID) genes encode negative-regulatory helix-loop-helix transcription factors. Id proteins typically act to block cell differentiation, and if overexpressed in cancer cells may help to promote tumorigenesis. In fact, ID1 and ID3 genes are overexpressed in epithelial ovarian cancer cells compared to normal ovarian surface epithelial cells. Thus, a major research focus of my laboratory is to uncover the functional implications of Id1 and Id3 expression in ovarian cancer cells.

Mouse models of ovarian cancer

Great strides have been made in our understanding of initiation and progression of specific cancers through the development of accurate mouse models of the human disease. Up until very recently, however, there have not been any transgenic or knockout mice that heritably develop ovarian cancer. In close collaboration with Dr. Gabriel DiMattia, we are rapidly developing multiple novel strains of transgenic mice to better understand the initiating genetic events of epithelial ovarian cancer.

Modeling ovarian cancer metastasis

The majority of ovarian cancer patients are first diagnosed with the disease when it has already spread from the primary site, or metastasized. Ovarian cancer is quite unique among the different types of carcinomas in that it very rarely leads to blood-borne metastasis; rather, ovarian cancer cells likely utilize alternative mechanisms to disseminate directly throughout the peritoneal cavity. Since most post-surgical treatment stratagies are to target and kill metastatic ovarian cancer cells hidden within the abdominal cavity, my laboratory is developing a cell culture and xenograft model system to dissect the underlying mechanisms controlling ovarian cancer metastasis.

BMP signalling in ovarian cancer

Bone morphogenetic protein (BMP) signalling is critically implicated very early in embryonic development to control the fate of cells and tissues. There is growing evidence that BMP signalling may be involved in several human cancers. We have demonstrated that epithelial ovarian cancer cells possess an intact autocrine BMP4 signalling pathway which influences the metastatic phenotype.