Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

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, acquiring the ability to adapt to a changing environment, which confers resistance to current therapies, and showing self-renewing potential, allowing them to re-establish the tumor post- treatment. Regardless of the size of the dedifferentiated portion of these ovarian and endometrial tumors, the poorer the survival of patients is compared to those suffering with high-grade carcinomas. Despite its aggressive nature and link to patient survival, the exact molecular mechanisms by which cancer cells acquire and maintain stem-cell like properties is not clear. Although some factors that participate in this cancerous cellular event are known, the role of proteins that expose genetic material by remodeling chromatin still remains to be discovered. It has been demonstrated that the mutations that inactivate proteins comprising the chromatin remodeling complex are often found in these aggressive forms of dedifferentiated cancers. The goal of my research project is to discover the interplay between known stem-cell promoting signaling pathways and these mutated proteins. 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 along 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.