Postdoc project: reversal of the mesenchymal transition in diffuse midline glioma

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 drug-combinations that reverse the mesenchymal phenotype and may be promptly translated to the clinic.

Therefore, the Postdoc will test different drug combinations on patient-derived cell cultures for their capacity to alter the phenotype of DMG cells. In addition he/she will determine drug effectivity and safety, drug synergy, and radiosensitizing capacities in both an in vitroand in vivo setting. Based on the results of these experiments, drug combinations will be selected that may be used as a backbone for future therapy.

Education and skills

We are looking for a highly motivated postdoc with an interest in Pediatric Oncology, and a background in cell biology/molecular biology. Experience with animal studies is a plus (article 9 certificate). Our group welcomes postdocs who have a natural level of scientific thinking, and like to collaborate and support other researchers. The candidate should have flexibility, attention to detail, excellent communication skills, and a good command of oral and written English.

We offer a temporary, full time position (36 hours/week) as a postdoc in an inspiring and inter-disciplinary research environment. You will start on a temporary position for the duration of one year that -when satisfactory- will be extended. Your gross monthly salary will depend on experience and background with a maximum of EUR 4466,- FGW 60. The Princess Máxima Center operates according to the collective labour 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.