Epigenetic Control of Gene Expression in Leukaemia and Haematopoiesis

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Acute lymphoblastic leukaemia (ALL) in children used to be a disease that was untreatable. Thankfully, general care for ALL has greatly improved so that ~90% of children are cured. Unfortunately, there are still rare subsets of ALL that have a tendency to relapse and are untreatable. We are trying to understand the molecular details of these rare, incurable ALLs in order to design new therapies. In order to do this, we study how epigenetics impacts gene regulation. Genes are made up DNA, and they reside in the nucleus, where they act as hardware for the cell that needs to be "read" in order to be functional. When genes are read (or what we call "activated")inappropriately, this can cause aberrant behaviour such as cancerous growth. Epigenetics is information that is not stored directly in the DNA itself. For example, some epigenetic information is stored in chemical modifications carried by histone proteins that interact with DNA in a structure called chromatin. It is becoming clear not only that aberrant epigenetic changes are common in many human diseases such as leukaemia, but that these changes by their very nature are reversible. Our goal is to help design therapies that can target these reversible epigenetic changes.