01/29/2010
Each year, OCRF awards millions of dollars in grants to researchers who are working to beat ovarian cancer. Our two newest grantees, Dr. Lin Zhang and Dr. Kathryn Terry, each received a $200,000 renewal, which will enable them to continue their work.
Lin Zhang, MD
Research Assistant Professor
University of Pennsylvania School of Medicine
“MicroRNAs, PI-3 kinase, and Ovarian Cancer Stem Cell Differentiation”
Project Summary
The lack of preventative strategies, early diagnostic methods and effective therapies to treat recurrent ovarian tumors has created a pressing need to understand its origins, and to identify molecular targets for therapy. Research in ovarian cancer has provided strong support for the “cancer stem cell” hypothesis, which proposes that a rare group of tumor cells have the unique ability to initiate and perpetuate tumor growth. These cancer stem cells can renew themselves (like embryonic stem cells do) and therefore contribute to cancer recurrence. Ovarian cancer stem cells may be highly resistant to chemotherapy; therefore, the development of more effective therapies for ovarian cancer requires effective targeting of these cells. MicroRNAs are short pieces of single-stranded RNA which control the expression of genes, and which may play roles in cancer stem cell behavior. This research project looks at microRNAs, and specifically at the role they play in regulating a signaling pathway called the “PI-3 kinase pathway.” Previous research funded by the OCRF enabled us to show that the PI-3 kinase pathway is one of the most critical involved in maintaining ovarian cancer stem cells’ ability to renew. Our current research is to explore whether the restoration of certain microRNA expressions will significantly suppress the PI-3 kinase pathway. Ultimately, we hope this will help us develop targeted ovarian cancer drugs which are directed at specific molecular aspects in signaling pathways of cancer cells.
Bio
Lin Zhang was awarded his medical degree in 1996. He served as Assistant Lecture at Beijing Medical University from 1996 to 2000. In 2000, he joined Dr. George Coukos’ laboratory as a postdoctoral research fellow at the University of Pennsylvania School of Medicine in Philadelphia, focusing on studies of the biology of human ovarian cancer. From 2003 to 2005, he was a Research Associate in Abramson Family Cancer Research Institute, University of Pennsylvania. In 2005, he joined the faculty as a Research Assistant Professor in the Department of Obstetrics & Gynecology and Center for Research on Reproduction and Women’s Health, University of Pennsylvania School of Medicine. He is currently Research Assistant Professor of Obstetrics and Gynecology. Dr. Zhang’s current research interests focus on the function of microRNAs in human ovarian cancer. He hopes to find better cancer molecular therapeutic approaches for potential clinical applications, particularly, in ovarian cancer patients.
Kathryn Terry, ScD
Assistant Professor of Obstetrics, Gynecology, and Reproductive Biology
Harvard Medical School/Brigham and Women’s Hospital
“Role of Genetic and Environmental Influences on Telomere Length in Ovarian Carcinogenesis”
Project Summary
Telomeres are the repeated DNA sequences at the end of chromosomes that serve as a “biological clock.” Each time a cell divides, its telomore length gets a little shorter until it reaches a critical length which signals the cell to stop dividing. Telomeres also help maintain the structural integrity of the DNA by protecting chromosomal ends. An enzyme called telomerase can add DNA back onto the telomeres, allowing the cell to keep dividing. Thus, telomeres have two potential roles in carcinogenesis. First, critically short telomeres can lead to unstable DNA that could initiate cancer growth. Secondly, activation of telomerase could enable cells to divide indefinitely.
Through OCRF funding, we studied whether common genetic changes may influence telomere length or ovarian cancer risk. We evaluated common variants in five genes involved in telomere maintenance in over a thousand women with ovarian cancer and a thousand control women. Based on this data, we have shown that some common genetic changes are associated with telomere length and ovarian cancer risk. Now, we plan to evaluate whether diet, obesity, or lifestyle factors interact with these genetic changes to influence telomere length or ovarian cancer risk. Furthermore, we will determine whether variation in these genes is associated with ovarian cancer survival.
Bio
Kathryn Terry, ScD is an Assistant Professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School and an Associate Epidemiologist at Brigham and Women’s Hospital. Her research on genetic susceptibility to ovarian cancer has focused on hormone receptors, the insulin-like growth factor pathway, and genes involved in telomere maintenance. She received her epidemiologic training at the Harvard School of Public Health and did her postdoctoral research at the Channing Laboratory, working on the Nurse’s Health Study. She continues her ovarian cancer research at the Obstetrics and Gynecology Epidemiology Center at Brigham and Women’s Hospital using data from the New England Case-Control Study.
