Diffuse midline glioma (DMG), including diffuse intrinsic pontine glioma, are highly malignant pediatric brain tumors, for which currently there is no cure. Due to their critical location in the brain and diffuse growth pattern, tumor resection is not feasible and the presence of an intact blood-brain barrier and intrinsic therapy resistance prevents effective chemotherapeutic treatment. Previous results from our laboratory indicate that reversal of the mesenchymal phenotype of DMG tumors by targeting the receptor tyrosine kinase AXL and histone deacetylases (HDACs) might reverse their diffuse growth-pattern and therapy resistance. Aim of this project is to identify additional/alternative therapeutic targets in DMG that may be used to develop an effective treatment strategy for these aggressive pediatric brain tumors. Therefore, the PhD student will perform functional genetic screenings using the CRISPR/Cas9 system in both an in vitro and in vivo setting. Based on the results of these screens, drug combinations will be selected that may be used as a backbone for future therapy.

We are looking for a highly motivated PhD candidate with an interest in Pediatric Oncology, and an MSc degree in (Medical) Biology, Neurosciences, or Life Science related studies. The PhD student should have technical experience in molecular biology and/or cell biology, and preferably has experience with animal studies (article 9 certificate). Our group welcomes PhD students who have a natural level of scientific thinking and who are enthusiastic, independent, and eager to learn. The candidate should have flexibility, attention to detail, excellent communicative skills, and a good command of oral and written English.

We offer a PhD project in an inspiring and inter-disciplinary research environment. The total duration of the project is 4 years (full-time). You will initially be appointed for a period of 1 year, and your performance will be evaluated by a training and supervision plan. Salary according to FWG 45 increment 6 (for the 1st year, increased to FWG 45 increment 10 in case of renewal). The Princess Máxima Center operates according to the collective labor agreement ‘CAO algemene ziekenhuizen’.

Princess Máxima Center for Pediatric Oncology

The Princess Máxima Center for Pediatric Oncology is a new nationwide research hospital concentrating healthcare, research and education with regard to cancer in children and is located in Utrecht, Science Park de Uithof. The institute has the ambition to give the best treatment to children with cancer with the highest cure rate and the least side effects to (often complex) anti-cancer treatment. The center brings together the best possible care and scientific research, creating a unique interdisciplinary institute for pediatric oncology in Europe. The research group of Dr Esther Hulleman focuses on highly aggressive brain tumors in children, such as pediatric high-grade glioma, and diffuse intrinsic pontine glioma (DIPG). Our laboratory performs translational research, aiming to improve survival and to decrease short- and long-term side effects in brain cancer patients by developing novel treatment modalities, varying from the identification of novel agents and combinational therapies, to drug delivery. To ensure clinical relevance, we work together with neurosurgeons, neurologists, pathologists, and pediatric oncologists.