As a group, genes encoding epigenetic regulators are among the most mutated genes in cancer.
The prevalence of these mutations across all cancer types is one of the most surprising findings from recent cancer genomics studies, yet our understanding of how they promote the disease is still limited.
We are investigating how disruption of epigenetic control - at the network level - favours phenotypic plasticity, enabling cancer cells to escape tumour-protective mechanisms and adapt to variable, and often challenging, environmental conditions. To do so, we combine CRISPR-based approaches to mimic the genetic alterations often observed in patients, in vitro and in vivo functional assays to examine cancer cell behaviour, and single cell transcriptomic analysis to dissect the molecular basis of cellular plasticity. We are particularly interested in understanding (i) the basis of epigenetic robustness in normal cells and how this is compromised in cancer; (ii) the functional consequences of destabilizing the network of epigenetic regulators at various stages of the disease; (iii) whether we can predict epigenetic vulnerabilities based on how the regulatory network is disrupted in a patient.