PhD student – Modelling Embryonal Brain Tumors with BCOR alterations for Understanding Biology and Therapy Development

The research project

Extensive molecular characterization has identified many novel pediatric brain tumor types over the last decade. Although not always histologically distinguishable, they present with unique clinical, genomic and transcriptomic features. This molecular classification has improved diagnosis and risk stratification, but not patient survival, as effective therapies are still lacking.

One of these novel tumor types, which we discovered, are embryonal brain tumors with BCOR alterations. Most of these tumors harbor internal tandem duplication (ITD) or gene fusions affecting BCL6 corepressor (BCOR), a POZ/zinc finger transcription repressor, or its homologue BCORL1. Based on the normal function of these genes, these aberrations will alter their role in transcriptional and epigenetic regulation. Together with our international collaborators, the first patient-derived in vitro and in vivo models were generated. Furthermore, our lab routinely generates various stem cell-derived brain organoids, in which we can introduce oncodriving events via electroporation of DNA plasmids. These genetically engineered brain tumor organoid (GEBTO) models can mimic human tumors.

To study tumor biology and to discover better treatment options for patients with embryonal brain tumors with BCOR alterations, you will further establish and fully characterize GEBTO models for BCOR alterations and patient-derived models on a molecular and histological level. Using these models together with (single cell) RNA-seq and (epi)genomic data of tumors and the developing human brain, you will investigate the potential cellular origin and elucidate how altered BCOR proteins function to induce tumors. Based on identified molecular pathways involved in these tumors and high-throughput drug screens on your models, you will aim to discover more effective drugs and improve the survival and quality of life for children with these tumors.

Your project is embedded in the overarching research program of our group and our international collaborations. While our group members will provide technical and bioinformatical support for your project, other researchers and clinicians in the Máxima will support you with their specific expertise. Furthermore, our collaborators abroad will provide you with their knowledge and skills.