Funding outcome

In Canada, it is estimated that 62% of women diagnosed with ovarian cancer will die from the disease. Just as alarming, 1 in 36 women will develop uterine cancer, making it one of the most common gynecological malignancies in Western nations. Most recently, cancers of the ovaries, endometrium and even lungs have been hypothesized to originate from the unchecked growth of dedifferentiated cells that most closely resemble embryonic stem cells. Specialized cells constituting these organs revert back to a simpler stem cell-like state and this dedifferentiation process is triggered by the switching of various protein signaling pathways. The end result is that the cells gain oncogenic properties. Although some factors that participate in this cancerous cellular event are known, the role of proteins that expose genetic material by remodeling chromatin still remain to be discovered. It has been demonstrated that the mutations that inactivate proteins comprising the chromatin remodeling complex are often found in aggressive forms of cancers affecting the lungs, ovaries and endometrium. The goal of my research project is to discover the interplay between known stem-cell promoting signaling pathways and these mutated proteins. In order to accomplish this goal, I will develop a model of dedifferentiated endometrial cancer in cells and animal models by mutating chromatin remodeling complex proteins. Assays to test for aggressiveness and stem-cell phenotype will be used in conjunction with the procedure of transplanting patient samples from dedifferentiated endometrial cancer cases into mouse models. Through this research, it is my objective to develop targeted therapies against undifferentiated stem-cell like cancers and hopefully improve survival outcomes. The benefits of understanding the biological mechanisms that allow cancer cells to bypass extensive regulation and become stem-cell like are two fold: it provides insight into the microenvironmental triggers of dysregulation and allows for therapeutics to target these dedifferentiated components in addition to the bulk of the tumor. This project has the potential to improve patient outcomes by not only changing therapeutic strategies but also influencing diagnsotic protocols and future cancer research.