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Cell cycle control and genome integrity
The de Bruin lab's mission is to establish fundamental principles of听cell cycle control involved in the听maintenance of genome stability and cancer initiation听and development. The lab has used a wide range of听model organisms and approaches听with a final goal of finding ways to identify and exploit therapeutic听opportunities听for cancer鈥檚 addiction to growth and proliferation.听Our group has established the molecular mechanism by which G1/S听transcription is inactivated during S听phase and how it is maintained in听response to replication stress. Our work indicates that G1/S transcription听plays an essential role in the tolerance to replication stress. Since听replication stress is a major cause of听genomic听instability in cancer, this represents a crucial new area for cancer studies in听the lab.听We recently established that cellular听growth has a central role in determining CDK inhibitor sensitivity. This听work听suggests that听independent of increased CDK activity, when cell division is inhibited, but听cell growth听continues, cells simply get too big to maintain a proliferative听state or maintain genome stability. Since听enhanced growth signalling is common听in cancers, this helps explain the anti-cancer efficacy of CDK听inhibitors. This听new insight is now being used to ask more specific questions to understand the听mechanisms听that determine a cell鈥檚 sensitivity to CDK inhibitors.