Epigenetic heterogeneity in cancer


Tumour initiation entails loss of cellular identity and acquisition of aberrant cellular properties.

We are interested in studying how epigenetics promote this oncogenic reprogramming process. We are currently performing focused CRISPR/Cas9-based, loss-of-function screens targeting proteins involved in the establishment and recognition of DNA methylation patterns, writer, readers and erasers of chromatin marks, chromatin remodelers and proteins controlling the high-order structure of chromatin, in order to identify epigenetic regulators which either prevent (tumour suppressors) or promote (therapeutic targets) tumorigenesis. To do so, we take advantage of a CRISPR library that we have recently generated, which allows targeting of individual epigenetic regulators in an arrayed format (Henser-Brownhill et al. Epigenetics 2017). We are also interested in characterizing how changes in the epigenome mediate the effect of classical oncogenes and understanding how cellular transformation corrupts the function of many wild-type epigenetic regulators and subverts developmental transcriptional programs.