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PhD defence

New dimensions of the cellular response to DNA damage

  • S.C. Moser
Date
Friday 14 November 2025
Time
Location
Academy Building
Rapenburg 73
2311 GJ Leiden

Supervisor(s)

  • Prof.dr.ir. J.M.M. Jonkers

Summary

Our DNA is constantly threatened by DNA damage; therefore, cells have evolved special repair systems to fix it. One of the most important repair factors is the BRCA1 gene. If women inherit a faulty BRCA1 gene, their cells cannot repair certain types of DNA damage properly, which greatly increases their risk of breast and ovarian cancer.

During my PhD, I studied how this DNA repair process works, why certain cancer treatments are effective against BRCA1‑mutated tumors, and how cancers manage to escape these treatments.

I discovered a new protein, called FIRRM, that works alongside BRCA1 and other repair proteins. FIRRM is responsible to remove another protein, RAD51, once it has finished its part in the repair process, and to bring in the final “cleanup crew”. Without FIRRM, cells are extremely sensitive to common cancer drugs like platinum chemotherapy and PARP inhibitors. This means testing for FIRRM levels could help determine treatment efficacy of certain cancer therapies.

Additionally, I found that PARP inhibitors do not just damage DNA, they also temporarily disrupt the “packaging” that holds DNA together and protects it. Disrupting the proteins that ensure this packaging, makes cancer cells more vulnerable to PARP inhibitors and other cancer therapeutics.

Together, these discoveries reveal new ways to predict treatment success and design smarter therapies, bringing us closer to personalized, more effective cancer care.

PhD dissertations

Approximately one week after the defence, PhD dissertations by Leiden PhD students are available digitally through the Leiden Repository, that offers free access to these PhD dissertations. Please note that in some cases a dissertation may be under embargo temporarily and access to its full-text version will only be granted later.

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