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.
Yinu Wang, PhD, is a postdoctoral fellow in Dr. Daniela Matei’s laboratory in the Department of Obstetrics and Gynecology at Northwestern University. Yinu received her BS degree in Pharmacy from Shenyang Pharmaceutical University in 2006, an MS in Biology from Western Kentucky University in 2011 and a PhD in Pharmacology in 2017 from Indiana University. As a graduate student working with Dr. Ken Nephew, she studied the mechanisms contributing to the emergence of chemoresistant recurrent tumors and focused on the functions of cancer stem cells (CSCs) driving tumor relapse. This work defined key signaling pathways contributing to the maintenance of ovarian CSCs. She also laid the groundwork for investigating epigenetic targeting of ovarian CSCs, by using DNMT methytransferase inhibitors. At Northwestern University, her research focuses on defining epigenetic signatures and the 3D chromatin nanoarchitecture of ovarian CSCs. She will link the physical properties of chromatin in ovarian CSCs with epigenetic mechanisms regulating gene transcription, to discover specific vulnerabilities of OCSCs. The ultimate goal is to target and eradicate CSCs, prevent tumor relapse, and improve survival rates of women with ovarian cancer.