Novel chromatin Effects of Oncogenic EZH2 mutations

In the last few years the cancer genome atlas (TCGA), has allowed us to identify numerous cancer-associated mutations. This information is critical, both in terms of disease prognosis, but also in the identification of novel therapeutic targets and for fulfilling the promises of personalized medicine. Sequencing studies from the TCGA have also highlighted the central role of epigenetic processes in cancer causation and progression and treatment. This presents us with a remarkable opportunity in translational medicine because, unlike DNA mutations, these epigenetic modifications are reversible and can be targeted by small molecule inhibitors.

Dr. Souroullas and his lab focus on molecular mechanisms and mutations in epigenetic regulators that contribute towards cancer development and which are also potential therapeutic targets. More specifically, Dr. Souroullas proposes to focus on the chromatin modifying enzyme EZH2 and to use basic scientific approaches to uncover how misregulation of EZH2 changes cells and allows them to become cancerous. The proposal will also investigate how misregulation of EZH2 cooperates with genetic mutations in other chromatin modifying genes, with the overall goal of understanding how changes in chromatin dynamics lead to the development of cancer.