Specialization
Radiobiology, Cancer, DNA repair, microscopy
Focus of research
Mechanisms driving repair of DNA double-strand breaks (DSBs) guard genome integrity in healthy cells but can also be harnessed to eradicate tumors in the clinic. The long-term research goal of my group is exploiting fundamental understanding of mechanisms driving DSB repair to develop and improve anticancer strategies. To achieve this goal, we are currently pursuing two interconnected research lines.
1. Visualization and analysis of molecular choreography of DSB repair responses in normal and cancer cells. We have recently constructed a unique microscopy setup that allows X-irradiation of living cells and imaging of the molecular choreography of DSB repair proteins at the damaged DNA, in real time. Using high-end microscopy techniques and cells (normal and cancer) expressing fluorescently tagged repair proteins, we want to understand how these proteins accumulate and interact with each other at damaged DNA, and how these processes can be exploited in anticancer therapies. Expanding this platform, we plan to construct, together with CERN, the world's first compact proton accelerator for imaging cellular responses to proton-induced DNA damage, which is highly relevant in the emerging context of proton therapy.
2. Improving hyperthermia-based clinical cancer treatments. Hyperthermia (HT) – temporary elevation of tumor temperature to 41-43 °C – alters many aspects of cellular metabolism, but its effects on DNA repair are of special interest in the context of cancer research and treatment. Our group has shown earlier that HT inhibits repair of DSBs by homologous recombination, explaining why HT sensitizes cells to DNA damaging agents in combination therapies for various types of cancer, including breast, bladder, head, neck, melanoma, soft tissue sarcoma and cervix. Unfortunately, the efficacy of HT treatments is negatively affected by insufficient heating of the tumors, relatively short therapeutic window and induction of thermotolerance. Recently, we found that inhibition of the chaperone protein HSP90 in vitro can overcome these problems. Our results thus establish HSP90 inhibition as a straightforward and efficient approach to improve HT treatment efficacy with no or limited systemic toxicity. Currently we are validating these findings in vivo, with the aim of translating them into a novel clinical cancer treatment within the next 5 years.