Vousden lab

Karen Vousden : Areas of interest

Introduction

We are investigating how wild type and mutant p53 activities contribute to various aspects of health and disease, focusing on the ability of p53 to control metabolism.

Our studies show that p53 plays a role in supporting the adaptation to nutrient starvation, both by providing antioxidant support and by promoting metabolic reprogramming.

The p53 tumour suppressor protein plays an important role in determining cell fate in response to stress. While the activation of p53 in response to sustained or irreparable damage can promote the permanent elimination of cells through the induction of apoptosis or senescence, p53 can also help cells to adapt to more moderate, transient stress by limiting oxidative stress and promoting cell survival.

We are investigating how wild type and mutant p53 activities contribute to various aspects of health and disease, focusing on the ability of p53 to control metabolism. Our studies show that p53 plays a role in supporting the adaptation to nutrient starvation, both by providing antioxidant support and by promoting metabolic reprogramming. This work has led to a more general interest in how changes in metabolism contribute to cancer development, and whether these changes lead to vulnerabilities that might be targeted for cancer therapy. We have found, for example, that dietary limitation of key amino acids can retard tumour progression.

Perturbations in the p53 pathway are found in almost all cancers, regardless of tissue of origin. Many tumours carry mutations in p53 that lead to the expression of a mutant p53 protein. In addition to losing the canonical activities of wild type p53 that drive cell elimination, these mutant proteins acquire functions that support cancer cells survive and metastasise. We are working to understand these functions of mutant p53 and testing the efficacy of targeting these proteins as a therapeutic strategy.

Selected publications