Using melanoma as a model, we established the key role of the Microphthalmia-associated transcription factor (MITF) in microenvironment-driven phenotype-switching in melanoma biology: MITF-low cells are drug-resistant, slow-cycling, tumour-initiating and invasive, while MITF expression suppresses invasiveness and promotes either proliferation or differentiation. Understanding how MITF is regulated, both transcriptionally and post-translationally, and how it integrates microenvironmental signals to determine melanoma phenotype is a key aim. More broadly, we are interested in how and why invasiveness is imposed and stem cells generated in melanoma, and how similar phenotypic states are produced in non-melanoma cancers.

To explain cancer progression we recently introduced the concept of starvation and pseudo-starvation to explain why cancer cells become invasive.

Our research is therefore aimed at understanding:
The drivers of phenotype-switching and senescence
The role of starvation and pseudo-starvation in cancer progression
The relationship between invasiveness and tumour initiation
The molecular mechanisms underpinning dormancy
The role of MITF-related factors in non-melanoma cancers