Chi Lam Au Yeung, PhD

2022 Early Career Investigator Grant

MD Anderson Cancer Center
Cancer-derived Exosomal miRNAs Modulate Ovarian Tumor Microenvironment

Project Summary
Epithelial ovarian cancer (EOC) is the leading cause of gynecologic cancer-related death in the United States. Annually, 21,000 women in the United States are diagnosed with EOC and approximately 14,000 women die from it. Most of the EOC patients are not diagnosed until the development of advanced stage disease. Although majority of these patients respond to chemotherapy after tumor removal surgery, many of them will develop recurrent disease within 1 year, become resistant to chemotherapy, and die from the disease. Survival of EOC has not improved much over the past decade. Thus, the development of new regimens for ovarian cancer treatment and improvement of survival of EOC patients are crucial. Recently, studies showed that various immune cell types play a role in modulating the tumor cells’ behavior and aggressiveness. Therefore, it is important to develop a strategy, which can enhance the ability of a particular immune cell called killer T cell, to kill cancer cells in the tumor tissue. Recent studies showed that ovarian cancer cells produced and secreted small RNA molecules (microRNAs) that can be transported to nearby cells via tiny vesicles shed from cells called exosomes to facilitate cell-cell communication and exchange of biological substances. We identified miR-181c-3p as a potential microRNA that is secreted in exosomes by ovarian cancer cells and is transported to other cell types including blood cells or immune cells in the nearby environment to exert functions. MiR-181c-3p is also expressed at high levels in tumor tissues obtained from long-term EOC survivors (> 8 years) than in short-term EOC survivors (< 5 years), suggesting that tumor cells which can make and secrete more miR-181c-3p can improve the patients’ survival rates. The main objective of the proposed study is to investigate the role of miR-181c-3p in improving EOC patients’ survival rates. We also propose to examine the efficacy of using miR-181c-3p for ovarian cancer treatment using animal models. The anticipated outcomes of the study will demonstrate the tumor-suppressive effect of miR-181c-3p and the effects of miR-181c-3p on suppressing blood vessels’ growth and on activating killer T cells, which will ultimately lead to suppression of ovarian cancer cells’ growth. The findings will provide a new perspective about the inter-relationship between different cell types in the nearby environment of ovarian cancer cells and ovarian cancer progression, and enable us to develop new strategies based on upregulating miR-181c-3p levels in ovarian cancer patients to improve their survival rates.

Bio
Dr. Chi Lam Au Yeung is an instructor in the Department of Gynecologic Oncology and Reproductive Medicine at the University of Texas MD Anderson Cancer Center. She earned her doctoral degree at the Chinese University of Hong Kong, studying the biological significance of the deregulation of microRNA expression in HPV-associated cervical cancer development. Her long-standing experience and expertise in gynecologic oncology has helped prepare her for a career dedicated to ovarian cancer research. Her postdoctoral training under the guidance of Dr. Samuel Mok was to investigate the importance of the omental tumor microenvironment in ovarian cancer progression using advanced technology. Her work was recognized by the Ann Schreiber Mentored Investigator Award from OCRA and multiple ovarian cancer-related fellowships from MD Anderson Cancer Center, including the Lupe C. Garcia Fellowship in Cancer Research and the Diane Denson Tobola Fellowship in Ovarian Cancer Research. As an instructor, Dr. Au Yeung continues to delineate underlying mechanisms that will lead to the development of alternative therapeutic strategies to improve patients’ survival. Dr. Au Yeung’s current research focuses on determining the importance of communication between different cell types in the omental microenvironment and delineating the underlying mechanism by which secretory proteins and exosomal molecules such as microRNAs modulate high-grade serous ovarian cancer progression, metastasis, and chemoresistance.