Milne Group: Epigenetics and Gene Regulation in Leukaemia
Aberrant epigenetic changes are a driving force in many human cancers. The focus of our lab is centred on understanding how epigenetics impacts gene regulation so that this information can potentially be used to develop new therapeutic strategies.
There has been much progress in treating human cancers, especially leukaemias, but most remain resistant to treatment. A potentially exciting approach is the development of small molecule inhibitors that specifically target aberrant processes in cancer cells but leave normal cells unharmed. In order to be successful, such an approach requires highly detailed information about normal and aberrant cellular processes on the molecular level, including better understanding the heterogeneity of leukaemia samples in patients.
Our lab studies epigenetic changes in leukaemia with a specific focus on specialized proteins called histones. Histones can have chemical modifications or “marks” attached to them that can code for gene activation or repression. 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. A great number of epigenetic proteins that have been implicated in human disease have also turned out to be enzymes that are involved in adding (“writing”), removing (“erasing”) or interpreting (“reading”) histone marks. Effective therapies are likely to require a cocktail of different inhibitors and will therefore depend on a clear understanding of how multiple epigenetic proteins cooperate in disease progression.
The focus of our lab is centred on understanding how epigenetics impacts gene activation and repression in normal and leukaemic cells. Enhancers are key regulatory elements that contribute to gene expression. They function in part by acting as docking sites for transcription factors, which can then activate appropriate target genes over long distances through mechanisms which have not been fully elucidated. Our current hypothesis in the lab is that aberrant epigenetic alterations at enhancers impact transcription factor binding patterns thus contributing to aberrant gene expression patterns in immune system cells as well is in leukaemia cells. We are particularly interested in a rare subset of leukaemias cause by mutations in the Mixed Lineage Leukaemia (MLL) gene that cause incurable leukaemias in children.
Our lab is inherently collaborative and uses a range of cutting edge technologies. This includes state of the art techniques for the analysis of gene regulation (ATAC-seq, ChIP-seq, Capture C, nascent RNA-seq), advanced molecular biology, genome editing, and computational biology.
Dr Marta Tapia
Dr Jon Kerry
Dr Ross Thorne
Dr Laura Godfrey
Part of the Milne lab work with OxStem Oncology, a subsidiary company of OxStem Ltd., a spinout company of which Tom Milne is a founding shareholder: