A number of enzyme catalyzed processes have been identified which modify the DNA molecule and its associated chromatin. These epigenetic processes modulate gene expression.  In some cases, drugs can modulate epigenetic processes and "rescue" the epigenetic status of diseased tissue. Despite the increasing link between epigenetic status at a molecular level and human disease and treatment, there are a surprisingly limited number of tools that allow researchers to directly probe epigenetic processes in vivo. New technologies for human molecular imaging that can report on enzymes which catalyze epigenetic transformations will revolutionize our ability to translate basic research to human therapy. To address this critical need, we are developing radiotracers for positron emission tomography (PET) that can provide molecular-level epigenetic information about the human brain. Our group is working on a series of radiotracers for a number of epigenetic targets including histone deacetylases,lysine demethylases, and DNA methyltransferases.  As we develop these imaging tools, we are using them to probe mechanisms of disease in the brain, heart, and in cancer.