Ovarian cancer is the leading cause of death from female reproductive tract cancer. While it is considered as a highly chemo-responsive tumor, the majority of women with high-grade serous ovarian cancer experience tumor relapse, associated with chemo-resistance. Ovarian cancer stem cells have been hypothesized to be responsible for poor prognosis, tumor recurrence, and drug resistance of ovarian cancer. Cancer stem cells share some of the normal stem cells’ characteristics, including the ability to self-proliferate, differentiate, and initiate tumor formation. While chemotherapy initially decreases the size of ovarian tumor, residual tumors after treatment are enriched in cancer stem cells. To reverse chemo-resistance and to prevent tumor relapse, new therapies are needed to eradicate the rare tumorigenic cancer stem cells. I hypothesize that the genetic code of ovarian cancer stem cells is modified through unique changes called the epigenome, which play an important role in their survival and tumor initiating properties.
The goal of my study is to define the epigenetic signatures of ovarian cancer stem cells. To achieve my goal, I will use a novel technique applicable to live cells called partial-wave spectroscopic microscopy. This technology is used for the first time in the study of cancer stem cells and in ovarian cancer and will show how the DNA is packaged inside cancer cells. My preliminary data demonstrates that the nuclei of cancer stem cells are much more compact that those of the non-stem cells, suggesting that the epigenome of cancer stem cells has unique characteristics. I will couple this novel imaging technique with a new sequencing method to reveal how gene expression is regulated in ovarian cancer stem cells. To further understand how the reading of the genetic code of stem cells can be modified, I will measure the effects of new drugs targeting the epigenome on the physical and molecular landscape of ovarian cancer stem cells. The long-term goal is to characterize the epigenetic regulation of gene signatures in ovarian cancer stem cells, allowing the rational design of new treatments to eradicate them.