My lab aims to understand the alterations in metabolism that take place in cancer and investigate whether extrinsic factors, such as diet, influence cancer metabolism and disease trajectory. We then want to uncover whether these dependencies can be exploited therapeutically.
My lab aims to understand the alterations in metabolism that take place in cancer and investigate whether extrinsic factors, such as diet, influence cancer metabolism and disease trajectory. We then want to uncover whether these dependencies can be exploited therapeutically and whether dietary modulation can increase their efficacy.
The altered metabolism of tumor cells is not a new concept in cancer biology. In the early 1920s, Otto Warburg established that cancerous tissues have an altered metabolism compared to their non-tumorigenic counterparts and satisfy their bioenergetic demands by shifting from oxidative phosphorylation (OXPHOS) to glycolysis. Although this shift decreases the efficiency of ATP production per molecule of glucose, it favors the shuttling of metabolic intermediates to biosynthetic processes required for macromolecule biosynthesis, i.e. production of proteins, nucleic acids and lipids. Cancer cells are able to satisfy at least part of their demand for lipids through anabolic metabolism of nutrient-derived carbon. We have shown that lipid metabolism is important under the unfavourable conditions encountered in the tumour microenvironment, uncovering several metabolic genes that are essential in cancer, including SREBPs, FABPs, ACSS2 and SCD. More recently, utilizing our 3D functional genomics pipeline we have identified recurrently altered novel tumour suppressors, whose loss results in a fundamental rewiring of cancer metabolism. Together, this gives us a number of biomarkers and tractable nodes to target in cancer, with which we can assess the intrinsic and extrinsic factors that drive tumour biology and disease progression.
To investigate these dependencies we utilise functional genomics (RNAi), genetic perturbation modalities (CRISPR/Cas9) and small molecule inhibitors in combination with cell culture techniques that are more similar to the unfavourable tumour microenvironment encountered in vivo (cancer cell line spheroids).
I studied Molecular Biology and Genetics at Royal Holloway (University of London) before moving to Imperial College London to complete a PhD in the role and regulation of forkhead transcription factors in breast cancer. In 2010 I moved to the London Research Institute (now the Crick Institute) to the lab of Prof. Almut Schulze to study cancer metabolism. This work focussed on identifying novel cancer-specific dependencies in cancer metabolism. As part of the Lipid metabolism consortium, we identified ACSS2 and SCD as fundamental dependencies of aggressive breast and prostate cancers.
In 2014 I moved to the lab of Dr. Rachael Natrajan identifying novel tumour suppressors in breast cancer. At the ICR we developed bespoke 3-dimensional (3D) screening pipelines and discovered novel genes, including CREBBP, KMT2C and NIPBL that impact disease progression and response to targeted therapies.