Research focus

DNA damage checkpoint pathways in cancer

Our DNA is constantly damaged by external factors, and persistent DNA damage can result in cancer. In order to prevent this, cells are equipped with pathways that respond to DNA damage, stop ongoing proliferation and activate DNA repair. These pathways are collectively called the DNA damage checkpoint. Paradoxically, besides being a cause of cancer, DNA damage is also a mainstay in the treatment of cancer. To kill cancer cells, radiotherapy and chemotherapy induce high levels of DNA damage. However, the overall inefficiency of radio/chemotherapy still points to ample room for improvement. The ability of cancer cells to repair therapy-induced DNA damage clearly contributes to this inefficiency. An appealing approach to sensitize cells for radio/chemotherapy is therefore to modulate DNA damage checkpoint responses. But it is currently unclear how the DNA damage checkpoint can be modulated to improve the responses to radio/chemotherapy.

In our research we use biochemical tools and microscopy to study how the DNA damage checkpoint functions in normal and cancer cells. One of our main interests centers around the question how the activity of DNA damage checkpoints is regulated (both activation and inactvation) and we specifically focus on cell cycle regulation as an important modifier of DNA damage checkpoint and DNA repair function. In addition, we investigate how we can optimallly monitor the DNA damage checkpoint in cancer tissue, and which DNA damage checkpoint components may be efficient targets for additive treatment during cancer therapy.