Chemotherapy resistance is a major obstacle to the successful treatment of ovarian cancer patients. Initially responsive, most ovarian tumors become drug resistant after successive rounds of standard chemotherapy. Understanding the molecular mechanisms of chemoresistance acquisition is key to develop new drugs that resensitize tumor cells to existing chemotherapy. In preliminary studies, Dr. Garcia-Bassets found that a regimen of cisplatin treatment in cultured ovarian epithelial cancer cells cause significant alterations in the levels of histone lysine methylation throughout the human genome affecting specific gene programs associated to cell survival and predisposition to chemoresistance. Lysine methylation of histones is a type of epigenetic (heritable) regulatory process that influences the levels of gene expression. In his study, Dr. Garcia-Bassets plans to fully characterize this cisplatin-mediated epigenetic response, identify the enzymatic activities that control this process, and test whether their suppression dismantles the drug resistant response. This proposal is expected to determine the value of pharmacologically targeting histone lysine methylation as a promising strategy to resensitize tumor cells to chemotherapy.