Only about 50% of the cells in ovarian cancer tumors are cancer cells. The rest are normal cells which have been “hijacked” by the cancer cells to promote tumor growth. In the experiments leading to this grant application we found that cancer cells recruit normal fibroblasts by changing the expression of microRNAs, which are small, non-coding RNA molecules that occur normally in human cells. We found that changes in only a few microRNAs are sufficient to reprogram a normal fibroblast to a cancer promoting cell. In this grant we propose to elucidate the mechanism with which microRNAs reprogram fibroblasts into tumor promoting fibroblasts and determine the role these fibroblasts play in the resistance of tumors to the most commonly used chemotherapy agent in ovarian cancer, carboplatin. We will also investigate whether specific genetic changes in ovarian cancer cells lead to differences in the reprogramming of fibroblasts. Our overall goal is to understand the role of microRNAs in ovarian cancer growth and to be able to restore normal microRNA function. Applying this knowledge could lead to novel therapies for patients suffering from ovarian cancer.
Our research team brings together the expertise of a biochemist, Dr. Peter, who has extensive experience in miRNA biology, Dr. Macleod, an expert on genetic mouse models, and Dr. Lengyel a physician and cell biologist.
Chair and Professor, Department of Obstetrics and Gynecology University of Chicago Ernst Lengyel, M.D., Ph.D., a Gynecologic Oncologist, is Chair and a Professor in the Department of Obstetrics and Gynecology at the University of Chicago. He graduated magna cum laude from the University of Munich in 1992 with a doctorate in medicine, followed by a research fellowship at MD Anderson Cancer Center. He completed his residency at the University of Munich and then entered the combined Gynecologic Oncology fellowship program at the University of California/San Francisco (UCSF) and Stanford. In 2004, after one year on the clinical faculty at UCSF, he joined the University of Chicago faculty as a research scientist and clinician. In 2008 he was awarded the Burroughs Wellcome Fund Clinical Scientist Award in Translational Research.
Dr Lengyel directs a translational research laboratory focused on understanding ovarian cancer metastasis and on developing and testing new treatments for ovarian cancer. Specifically, he looks at interactions of ovarian cancer cells with the normal cells surrounding them to understand how the cellular microenvironment affects the growth of cancer cells. The major goal of his laboratory is to translate his research findings into novel therapeutic treatments that will improve the survival of those with this devastating disease. His primary clinical focus is the surgical treatment of patients with ovarian cancer.
For more information on Dr. Lengyel’s research and clinical practice at the University of Chicago see: