Scientific Programmes

Molecular Oncology Programme

Genomic Instability Group

Overview

DNA damage is the source of pro-cancerous mutations. In addition, recent evidence suggests that the reverse connection might also exist; namely, that oncogenes can promote the generation of DNA damage. However, the nature of the damage caused by oncogenes is still poorly understood. Our laboratory has centred its research on trying to understand how cells respond to ‘replicative stress’ (RS); a type of DNA damage that arises unavoidably each time a cell replicates its DNA, and that is mainly prevented by ATR and Chk1 kinases. Unfortunately, the essential nature of these kinases imposes important limitations on their investigation, particularly at the organismal level. In order to overcome these limitations, a significant part of our work over these last few years has focused on the development of cellular and animal tools for the study of ATR and Chk1. These tools include mice with enhanced or limited ATR-Chk1 function, cell systems in which the pathway can be activated at will, and chemical inhibitors of the ATR kinase. Our studies have revealed the impact of RS in cancer and ageing, and have resulted in drugs that can be used to test our conceptual approaches to cancer therapy. All in all, our main goal is to understand how genome maintenance is safeguarded – particularly during replication – and to exploit this knowledge in the fight against cancer.