René Medema Group
Cell Division and Cancer
The aim of my group is to unravel the mechanisms that protect genomic integrity, and study how these are affected in cancer. My group has studied cell cycle control by cell cycle checkpoints in order to gain a better understanding how cell division is influenced by damage to the DNA. In parallel, my group has studied how chromosome segregation is controlled, how chromosome segregation errors are prevented, and how these errors affect the fitness of tumor cells.
A major focus of my work in the last 5 years has been to understand how cells recover from a DNA damaging insult, such as those caused by various anti-cancer drugs. We are trying to unravel the mechanisms that promote cell cycle re-entry once the checkpoint is switched off and how this is coordinated with DNA damage repair. For this, we have established a number of assays involving FRET-based biosensors and fluorescent markers to monitor the appearance and repair of double-stranded DNA breaks, as well as inactivation and reactivation of the cell cycle machinery, in single living cells.
To gain a better understanding of fidelity of chromosome segregation, my group has focused on the mechanisms underlying bipolar spindle assembly, and attempted to exploit chromosome segregation errors as a means to selectively target the fitness of cancer cells. We have discovered that lagging chromosomes in cancer cells can break during telophase and cytokinesis, and we have developed small molecule inhibitors of TTK/Mps1, an essential component of the spindle assembly checkpoint that we can use to induce chromosome segregation errors. A major focus for the future will be to utilize this drug in mice to resolve how chromosome segregation errors affect tumor fitness and overall ageing.