Dr Barrie Peck
Group Leader
Overview
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.
Research
My lab aims to understand the alterations in metabolism that take place in cancer and investigate intrinsic and extrinsic factors, such as diet, that influence cancer metabolism, disease trajectory and treatment response. We then want to uncover whether these dependencies can be exploited therapeutically.
The altered metabolism of tumour 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 favours 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, utilising our 3D functional genomics pipeline we have identified recurrently altered novel tumour suppressors, such as CREBBP, 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 inhibitor screens in combination with cell culture techniques that are more similar to the unfavourable tumour microenvironment encountered in vivo (cancer cell line spheroids).
Current projects:
- Targeting lipid desaturation in aggressive cancers
- Investigating the role CREBBP loss plays in altering metabolism in Small Cell Lung Cancers and Lymphomas
- Investigating novel tumour suppressors as regulators of cancer metabolism in Breast Cancers
- Establishing reductases as novel actionable targets in clear cell Renal Cell Carcinomas
Key Publications
- The glutathione redox system is essential to prevent ferroptosis in clear cell renal cell carcinoma cells. Oncogene (2018) 37(40):5435-5450. PMID: 29872221
- Inhibition of fatty acid desaturation is detrimental to cancer cell survival in metabolically compromised environments. Cancer & Metabolism (2016) 4:6. PMID: 27042297
- 3D modelling identifies novel genetic dependencies associated with breast cancer progression in the isogenic MCF10 model. Journal of Pathology (2016) 240(3):315-328. PMID: 27512948
- Acetyl-CoA Synthetase 2 Promotes Acetate Utilization and Maintains Cancer Cell Growth under Metabolic Stress. Cancer Cell (2015) 27(1):57-71. PMID: 25584894
Major Funding
- 2019-2022 – Barts Charity, ‘Understanding the role of cancer metabolism at the nexus of diet and tumour microenvironment’
- 2023-2029, Cancer Research UK (CRUK) Career Establishment Award, ‘Understanding and exploiting Acetyl-CoA metabolism in Small Cell Lung Cancer’, ~£1.1M
Other Activities
- Member of the British Association for Cancer Research
- Member of the European Association for Cancer Research
- Breast Cancer Now grants committee member
Biography
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.
