I completed a PhD in virology at the National Institute for Medical Research, London, UK. I then did postdoctoral work in Pierre Chambon’s lab in Strasbourg, France, where I developed an interest in transcription regulation before taking up a position at the Marie Curie Research Institute, Oxted, UK, to continue working on gene regulation, both in S. cerevisiae, as well as in melanocytes and melanoma. In 2008 I moved to the Ludwig Institute, Oxford, where I continue to examine the role of signaling and transcription in melanoma biology, with the aim of developing novel and anti-cancer therapies that take tumor phenotypic heterogeneity into account.
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, tumor-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 tumor initiation
• The molecular mechanisms underpinning dormancy
• The role of MITF-related factors in non-melanoma cancers
Ludwig Institute for Cancer Research, Oxford
Nuffield Department of Clinical Medicine
Old Road Campus Research Building
off Roosevelt Drive, Headington, Oxford, OX3 7DQ, UK
T +44 (0) 1865 617507