Two Synergy Projects explore processes that can shape how cancer cells change. Researchers are investigating the role of cell metabolism in genome stability and developing a new way to study DNA repair after chemotherapy.
Cancer cells can change as tumours grow and respond to their environment and treatment. Changes in how cells use energy and how they repair DNA damage can play a role in this process.
Two Synergy Projects, supported by the Alpe d'HuZes/KWF Fund, are looking at these processes from different angles. One investigates how changes in cancer cell metabolism can affect chromosome stability. The other develops a new method to study how cells repair DNA damage caused by chemotherapy.
How can metabolism affect cancer cells?
Cancer cells often change the way they use energy, particularly when oxygen levels inside a tumour are low. These changes may also affect how chromosomes are maintained when cells divide.
Oncode Institute researchers Jurica Matkovic (UMC Utrecht) and Marco Novais-Cruz (Princess Máxima Center) are investigating this connection in Metabolic reprogramming as a cell fate switch.
The team will study how changes in metabolism under low-oxygen conditions affect chromosomes and contribute to genomic instability. By combining different research methods, they aim to better understand the link between a cancer cell's metabolic state and the stability of its genome.
Following DNA repair over time
Several commonly used chemotherapy drugs cause damage that can compromise DNA integrity. Cells have mechanisms to repair this damage, but some of the proteins involved in the different stages of this process are still unknown.
Oncode Institute researchers Dick Zijlmans (Radboud University), Carlota Davo Martinez (Hubrecht Institute) and Marjolein van Sluis (Erasmus MC) are developing a new way to study this process in Time-machine proteomics: mapping protein interactions throughout different reaction steps of DNA repair.
Current methods can miss proteins that are involved only briefly during DNA repair. The team will develop a method that allows them to track proteins involved at different stages of the process.
This could provide a more detailed picture of how cells repair DNA damage caused by chemotherapy and offer a new way to study other DNA repair processes.
What the researchers say
Meet the researchers behind these collaborations and discover what excites them most about their projects.
Metabolic reprogramming as a cell fate switch: How hypoxia drives genome instability
Jurica Matkovic
“Having discovered that a NAD+/NADH redox switch is essential for faithful chromosome segregation, we are excited to transfer this finding to a tumour context. This project allows us to explore how hypoxia driven metabolic rewiring subverts this fundamental regulatory mechanism, directly linking the tumour microenvironment to catastrophic genomic instability.”
Marco Novais-Cruz
“This project brings together complementary expertise to tackle a complex question. I’m particularly excited to connect hypoxia-induced metabolic rewiring with genome integrity. This synergy offers a unique framework to translate fundamental insights into therapeutic strategies that may limit tumor evolution and overcome treatment resistance.”
Time-machine proteomics: mapping proteins interaction throughout different reaction steps of DNA repair
Carlota Davo Martinez
‘I am excited to collaborate and bring DamID-based proximity labelling to the DNA repair field, which will open new possibilities to dissect multistep chromatin-associated processes.’
Dick Zijlmans
“I am excited to apply proximity proteomics to generate a time-resolved map of DNA repair. Capturing proteins at each stage will help us better understand this process and shed light on the cytotoxic effects of chemotherapeutics.”
Marjolein van Sluis
“I am excited to collaboratively study the consecutive of DNA-Protein crosslink repair complexes in time and get a better mechanistic understanding of DNA-Protein crosslink repair induced by chemotherapeutics.”
About the Oncode Synergy Projects 2026
Inside the Synergy Projects 2026 is a series highlighting the collaborative research projects supported through the Oncode Synergy Projects 2026 programme. Supported through the collaboration between Alpe d'HuZes, KWF and Oncode Institute, the programme brings together Oncode researchers from different institutes and disciplines to develop innovative approaches to cancer research.