Neurosurgical Research
Identifying universal therapeutic targets in heterogeneous brain tumors
Identifying universal therapeutic targets in heterogeneous brain tumors
The inter- and intra-tumoral heterogeneity of GBM is a major obstacle for successful therapy. Deciphering neurodevelopmental programs in GBM that may provide tumor-wide therapeutic targets is a general aim in the field, but has not yet been accomplished. Our unpublished data show that pathways controlling glioma stem cell (GSC) differentiation offer new treatment options with potentially broad clinical impact for neurooncology. As a preclinical model for this doctoral project we generated a transgenic, lineage-tracing mouse model for GBM in which GSCs and their differentiated progeny are readily identifiable by different fluorescent reporters. The model is genetically versatile and can generate a palette of histopathologically distinct GBM with broad differences in overall survival time. Despite this strong inter-individual heterogeneity all GBM subsets exhibited common developmental traits with strong therapeutic potential. In this project we aim at identifying signaling cues for GSC differentiation in the transgenic mouse model that have broad pathological relevance for human tumors and thereby provide impactful data for neuroscience and translational strategies for neurooncology. For this project we will use multi-omics read-outs of human and mouse brain (tumor) samples, bioinformatics, advanced microscopical technology, pharmacology and neurosurgery to fulfil our aims.
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