PhD student DNA repair in kidney cancer Groningen • UMC Groningen

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The PhD candidate will work on a research project that was recently awarded by the Dutch Cancer Society (KWF), and focuses on a DNA repair function of the Von Hippel-Lindau (VHL) tumor suppressor gene. The VHL gene is an important tumor suppressor gene that is mutated in the majority of clear-cell Renal Cell Carcinomas (ccRCC), the most common kidney cancer subtype. It encodes the pVHL protein, which has a well-documented function in oxygen sensing. Surprisingly, recent data from our lab indicate that pVHL has a second function. A CRISPR-based genetic screen and follow-up validation assays show that pVHL promotes repair of a dangerous type of DNA damage; the DNA double-strand break. This suggests that VHL-mutant ccRCC has a DNA repair defect. This finding sheds new light on the tumor suppressor functions of VHL, and may guide the development of novel therapeutics targeting VHL-deficient ccRCC. Therefore, this research project aims to delineate the mechanistic details of the DNA repair function of pVHL. Furthermore, defective repair of DNA double-strand breaks is known to sensitize tumor cells to drugs that further inhibit DNA repair pathways in the cell. A second aim of this project is therefore to investigate the therapeutic potential of DNA repair inhibitors as a new treatment paradigm against VHL-mutant ccRCC.

Job description
The project involves standard molecular and cell biology techniques (cell culture, DNA cloning, PCR, western blot, flow cytometry, microscopy), as well as drug sensitivity assays, CRISPR-based genome editing, genetic screens, mass spectrometry and next-generation sequencing approaches. The PhD candidate is expected to plan, execute and analyze experiments within the project, and disseminate the findings in publications, poster presentations and talks both within the UMCG as well as at (inter)national meetings. The PhD candidate will manage independent research lines, but the project is highly collaborative: it involves collaboration with other members of the lab as well as with research groups in other institutes.

A PhD position for 4 years is available and will be performed in the lab of Prof. Marcel van Vugt. Supervision will be done by dr. Bert van de Kooij, senior researcher in the lab of Prof. Marcel van Vugt. The lab is focused on the DNA damage response, DNA repair, cell cycle control and DNA damage-induced inflammatory signaling. The research group is embedded in the Department of Medical Oncology of the University Medical Center Groningen (UMCG) in the Netherlands, where oncological patient care is coordinated with preclinical and fundamental research on the biology and treatment of cancer. The Department of Medical Oncology participates in the research institute MoHAD (Mechanisms of Health, Aging and Disease), in which molecular biologists, pharmacists and clinicians work closely together creating an optimal and excellent environment where the biological behavior of cancer cells, molecular imaging of tumors and novel approaches of cancer targeting are studied.

The PhD student will be part of an enthusiastic and multidisciplinary research group and should have the following requirements:

• MSc degree in Life Science (Biology, Molecular Biology, or related).
• Experience in standard molecular and cell biology techniques.
• An enthusiastic, self-motivated, ambitious, and proactive team player.
• Good communications skills in written and spoken English.

The starting date is envisioned to be November 1st, 2025.

A full-time appointment for a period of four years (36 hours a week) to be concluded with a PhD examination. After one year, the performance of the candidate will be evaluated to decide whether there is sufficient progress to expect a successful completion of the PhD thesis within the coming three years. Your salary will be € 3.108 gross per month in the first year, and up to a maximum of € 3.939 gross per month in the last fourth year, based on a full-time appointment. Additionally, the UMCG offers an 8% holiday allowance, an 8.3% year-end bonus.The conditions of employment comply with the Collective Labour Agreement for Medical Centres (CAO-UMC).

Links
UMCG research Medical Oncology
UMCG research L.W. van de Kooij
UMCG research van Vugt Lab DNA Damage