Scientific Programmes

Molecular Oncology Programme

Genomic Instability Group

Overview

DNA damage is the source of pro-cancerous mutations but recent evidence has suggested that the reverse connection might also exist; namely, that oncogenes can promote the generation of DNA damage. However, the nature of the damage that is 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, every time that a cell replicates its DNA, and which is mainly prevented by ATR and Chk1 kinases. Unfortunately, the essential nature of these kinases has significantly limited their study, particularly at the organismal level. In order to overcome these limitations, a major part of our work these past 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 on cancer and ageing, and have resulted in putative drugs that can be used to test our conceptual approaches to cancer therapy. Overall, our main goal is to understand how genome maintenance is safeguarded – particularly during replication – and to exploit this knowledge as a way to fight cancer.