In keeping with our long-term interest in developing and applying fluorescent DNA bases, we are developing new molecular tools for studying DNA repair enzymes and their relationships to cancer and inflammation. We are actively designing modified DNAs that yield fluorescent signals to report on repair of specific types of damage; these are being used in vitro in screens of inhibitors, and in measuring enzyme activities in tissue samples of cancer patients. Screening of enzymes in vitro, followed by synthesis and testing of analogs, has led to the development of a number of potent small-molecule modulators of DNA repair pathways. We are collaborating with multiple cancer biology groups on this project. We are working to identify new leads for diagnosis and treatment of some of the more difficult-to-treat malignancies, including lung, colorectal, and pancreatic cancer.