A functioning DNA methylation system is essential for normal human development and is often disrupted in disease, especially cancer. DNA methylation involves the addition of a molecule, called a methyl group, to the DNA, which results in silencing of gene expression. Precisely how ‘painting’ with DNA methylation regulates gene expression patterns is still unclear. Even more unclear is how DNA methylation contributes to complex diseases, such as cancer, in which it is often disrupted. Understanding the function of DNA methylation in normal human biology, will allow us to understand its role in disease, with the ultimate goal of developing new drugs that target DNA methylation.
My group studies DNA methylation mechanisms in CD4+ T-cells, a type of white blood cell that orchestrates the immune response to external threats such as bacteria and parasites and internal threats, such as cancer. In order to respond to such challenges CD4+ T-cells rapidly change into one of several different cell-types, each with specific but very different roles to play in the immune response. During this process, called differentiation, the CD4+ T-cells change the DNA methylation patterns across the entire genome. How T-cells achieve this feat is unclear, but it is key to their function.
Using state of the art gene-editing approaches combined with genomics analysis we have begun to understand the function of DNA methylation in human T-cell biology. We then use this information to shed light on why DNA methylation is targeted for disruption in many cancers, focusing on the childhood cancer, T-cell acute lymphoblastic leukaemia (T-ALL).
Importantly, as many of the enzymes that control DNA methylation can be targeted with drugs and nutraceuticals (i.e. vitamin C), it is our ultimate aim to use our improved understanding of DNA methylation to guide the use of such compounds in the treatment of T-ALL and other malignancies.