Professor of Oncology
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, where I continue to examine the role of signalling and transcription in melanoma biology, with the aim of developing novel and anti-cancer therapies that take tumour 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, 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
Starvation and Pseudo-Starvation as Drivers of Cancer Metastasis through Translation Reprogramming.
García-Jiménez C. and Goding CR., (2019), Cell Metab, 29, 254 - 267
BRN2 suppresses apoptosis, reprograms DNA damage repair, and is associated with a high somatic mutation burden in melanoma.
Herbert K. et al, (2019), Genes Dev, 33, 310 - 332
Targeting MC1R depalmitoylation to prevent melanomagenesis in redheads.
Chen S. et al, (2019), Nat Commun, 10
A TFEB nuclear export signal integrates amino acid supply and glucose availability
Li L. et al, (2018), Nature Communications, 9
Translation reprogramming is an evolutionarily conserved driver of phenotypic plasticity and therapeutic resistance in melanoma
Falletta P. et al, (2017), Genes & Development, 31, 18 - 33
Paradoxical activation of AMPK by glucose drives selective EP300 activity in colorectal cancer.
Gutiérrez-Salmerón M. et al, (2020), PLoS biology, 18
Organotypic Models in Drug Development "Tumor Models and Cancer Systems Biology for the Investigation of Anticancer Drugs and Resistance Development".
de Oliveira ÉA. et al, (2020)