- Department / Institute
- LMU University Hospital, Neurosurgical Research
- Subject area
- Neuroscience, Neurooncology
- Name of supervisor
- Prof. Dr. Rainer Glass
- Number of open positions
- 1
- Project title
- Cellular and molecular traits controlling blood-tumor-barrier formation in the brain
- Language requirements
- Fluency in English
- Academic requirements
- 4-year Bachelor's plus Master's degree; applicants should belong to the best 20% of their year (please provide credentials)
- Study model
- Full doctoral study model: 36 or 48 months
Project description
Glioblastomas (GBM) are devastating, treatment-refractory brain tumours. Treatment resistance of GBM is supported by extensive interaction of non-neoplastic brain cells (tumor parenchyma) with bona fide GBM cells. The largest tumor-parenchymal components are GBM associated myeloid cells (GAM) and the tumor vasculature. GAM can make up to 40% of the tumor mass and e.g. drive GBM invasion. The aberrant vasculature in GBM maintains a residual barrier function of the blood-tumor interface (blood-tumor barrier; BTB). The BTB is subject to regional heterogeneity in GBM and can obstruct the entry of therapeutics in large parts of the tumor. Hence, GAM and BTB constitute major obstacles for clinical care of GBM and promote GBM relapse.
In this project we will study the cell biological and molecular mechanisms controlling the morphology and tightness of neoplastic vessels of the brain. We will focus on signaling cues for GAM-induced BTB formation. To this end we will inspect GBM biopsies, perform in vitro assays as well as genetic manipulations of mouse models and tumour cells. Read-outs will comprise RNAseq (bulk and single cell), RT-qPCR, flow cytometry, Western blotting, immunohistochemistry and histological inspection. The project aims at improving the efficiency of conventional chemotherapy and new targeted treatments for GBM.