Vousden lab

p53 and Metabolism Laboratory

: Areas of interest

Introduction

Our metabolic studies have focused on how cancer cells use amino acids. We have shown that most cancers have a high demand for the amino acid serine, which is necessary for many biological processes including DNA synthesis and anti-oxidant defence. While cells are able to synthesise their own serine, in many cases we see that cancer cells are dependent on the uptake of serine from their surroundings.

Based on this observation, we have shown that dietary limitation of serine can help to slow down cancer development and improve the response to chemotherapy. The sensitivity of cancers to this approach is dependent on the genetic alterations that caused malignant development and we believe that understanding the relationship between oncogenic changes and metabolic requirements will allow us to develop bespoke diets that are customized to patients, their tumours and their therapy – an approach we term “precision nutrition”.

Our long-standing interest in the p53 tumour suppressor protein is built on the observations that p53 can function to eliminate incipient malignancies. However, our more recent studies have shown that p53 also plays a role in supporting the adaptation to nutrient starvation, both by providing antioxidant support and by promoting metabolic reprogramming. Perturbations in the p53 pathway are found in almost all cancers, regardless of the tissue of origin. Interestingly, many tumours carry mutations in p53 that lead to the expression of a mutant p53 protein.

We have shown that while these mutant p53s lose the canonical activities of wild type p53 that drive cell elimination, some of them retain activities related to cell survival and adaptation. Furthermore, mutant p53 proteins can acquire new functions that support cancer cells survive and metastasise. We are working to understand the different contributions of mutant p53 to tumorigenesis and testing the efficacy of targeting these activities as a therapeutic strategy.
 

Selected publications