Our laboratory is focused on the mechanisms by which epigenetic processes become mis-regulated in cancer and contribute to the disease phenotype. We focus on the role of DNA methylation in controlling the expression of genes during normal development and in cancer. Our work has shifted to an holistic approach in which we are interested in the interactions between processes such as DNA methylation, histone modification and nucleosomal positioning to structure the epigenome and we want to determine how mutations in the genes which modify the epigenome contribute to the cancer phenotype. We have had a longstanding interest in the mechanism of action of DNA methylation inhibitors both in the lab and in the clinic. In the clinic, we are working with several major institutions to bring epigenetic therapies to the forefront of cancer medicine.
Epigenetics may be defined as mitotically heritable changes in gene expression which are not caused by changes in the DNA sequence itself. Epigenetic processes establish the differentiated state of cells and govern how genes are used in the different cells in our bodies to allow organs and different cell types to function correctly and inherit their properties through cell division. These processes can go wrong during the formation of diseases including cancer and thus change the behavior of cells so that they don’t perform as they should. Importantly, many of these changes are potentially reversible and can be changed by treatment with appropriate drugs. Since epigenetic processes are at the root of biology they have implications in all of human development and disease.