Determining the therapeutic efficacy of epigenetic drugs in ovarian cancer

Because cancer and many diseases arise from a combination of genetic propensity and the response of cells to external factors mediated through changes to the expression of key genes, it is important to understand epigenetic regulation. The epigenome is crucial to the changes of gene expression and there is now strong evidence that epigenetic alterations are key drivers of cancer progression. However, very few drugs targeting epigenetic modifiers have been successful, in part due to the lack of effective means to select the patient group in which they will be most effective. This highlights an urgent need to understand the molecular basis of epigenetic changes in aggressive cancer Therefore, understanding the role of these enzymes in cancer progression using patient-derived samples will aid in improving existing therapies and potentially identify new targets for treatment.

Hypothesis

We hypothesise that:
1.deregulation of epigenetic modifiers is responsible for cancer progression and metastasis
2.inhibiting the activity of epigenetic modifiers will allow re-expression of genes that may improve outcome of cancer patients.

Aim

The overall goal of this study is to develop a novel therapy targeting epigenetic modifiers and validate the epigenetically-suppressed gene signature that predicts outcome in aggressive cancer patient samples to generate a signature-based diagnostic tool that can identify cancer patients at high risk of recurrence and metastasis

Approaches
1.Cellular models and treatments.
2.Characterisation of the epigenetic modifier change by RNA-seq.
3.Promoter methylation analysis.
4.Protein complex purification and proteomics.
5.Immunoprecipitation assays.
6.Characterisation of putative target genes by ChIP-seq.

For more information on this group: http://www.qimrberghofer.edu.au/lab/control-of-gene-expression/