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 metabolism, 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 & development, 33, 310 - 332
Targeting MC1R depalmitoylation to prevent melanomagenesis in redheads.
Chen S. et al, (2019), Nature communications, 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
The integrated stress response effector ATF4 is an obligatory metabolic activator of NRF2.
Kreß JKC. et al, (2023), Cell reports, 42
DNA damage-induced interaction between a lineage addiction oncogenic transcription factor and the MRN complex shapes a tissue-specific DNA Damage Response and cancer predisposition.
Binet R. et al, (2023), bioRxiv