Grant: Project Grant

Background. DNA methylation is an "epigenetic" chemical mark on DNA that punctuates and "programs" the "book of life". The Szyf lab pioneered the idea that different environmental experiences change DNA methylation and that changes in DNA methylation are involved in cancer and other diseases and that "epigenetic" drugs could cure cancer. The question and its importance. Although drugs that target DNA methylation are currently used in the clinic to treat certain blood cancers the currently available drugs are rather crude and nonspecific. After 40 years of research in this field we still don't know which methylation events in the genome are critical and should be used for diagnosis or targeted for epigenetic therapy. To rationally design epigenetic drugs, we need to understand what are our targets. Objectives of the research. The project will use gene editing technologies to alter the state of methylation of specific sites in genes to demonstrate their specific role in gene action and pathology. Impact on health and significance: These studies will guide new approaches to DNA methylation targeted drugs, will test the feasibility of using gene editing technology to alter DNA methylation in specific genes for treating diseases such as cancer or diabetes and will define important "functional" DNA methylation sites in the genome for designing new DNA methylation based diagnostics.