MMR deficiency is associated with increased risk of developing ovarian cancer and is the most common cause of hereditary ovarian cancer after Brca1 and Brca2 mutations. A functional MMR system is required for the detection of damaged DNA created by cisplatin. When MMR is deficient, cells can continue to proliferate in spite of DNA damage caused by cisplatin, and are thus resistant. Moreover, when MMR is deficient, unrepaired areas of DNA accumulate, resulting in microsatellite instability (MSI), which is the hallmark lesion of MMR-deficient cancers. However, a significant fraction of MSI-positive cancers express MMR genes at normal levels and do not carry a detectable mutation in or hyper-methylation of known MMR genes. These observations suggest that additional factors in MMR pathway may exist to explain the molecular mechanisms that underlie drug resistance in ovarian cancer. The work proposed here will be significant because when it is complete, we will understand the key components of MMR pathway that are responsible for ovarian cancer development, therapeutic resistance and treatment.
Dr. Gong is currently an Assistant Professor in the Cleveland Clinic Lerner College of Medicine, and Assistant Staff in Department of Cancer Biology of Cleveland Clinic. He received his Ph.D. from Giessen University at Germany. Dr. Gong pursued postdoctoral training in the laboratory of Dr. Junjie Chen at Yale University and MD Anderson Cancer Center, where he studied the DNA damage signaling pathway and DNA replication. Dr. Gong’s current research interests focus on synthetic lethality and synthetic viability: DNA repair pathway choice in ovarian cancer treatment. In addition to the Ovarian Cancer Research Fund Liz Tilberis Early Career Award, Dr. Gong’s work is also supported by NCI RO1 grant.