Project Details
Projekt
Spatio-temporal profiling of microglial heterogeneity and dynamics in glioblastoma
Applicants
Professor Dr. Martin Fuhrmann; Dr. Felix Nebeling
Subject Area
Molecular Biology and Physiology of Neurons and Glial Cells
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 559395868
Glioblastoma (GB) is the most common and malignant brain tumor in adults (Ostrom et al., 2023). The tumor microenvironment (TME) significantly influences GB progression, with microglia comprising a substantial portion of the non-neoplastic cells (Buonfiglioli & Hambardzumyan, 2021; Solomou et al., 2024). While microglia interact with GB cells, the complexities of these interactions are not well understood and identifying immunomodulatory targets to counteract local immunosuppression in the TME remains challenging. We have recently identified a biphasic micro-glial response to sustained GB-infiltration deep in the Corpus Callosum in vivo, along with distinct microglial subsets at the tumor margin that suggest differential recruitment (Nebeling et al., 2024). However, the precise spatio-temporal dynamics and molecular mechanisms governing microglia-GB interactions remain unclear, and microglia-targeted therapies have yet to succeed in clinical trials. To address these gaps, we will analyze microglial behavior in response to GB infiltration across distinct tumor niches using advanced three-photon microscopy and spatial omics techniques. We will also explore strategies to modulate microglia-GB crosstalk to restore normal microglial function and mitigate tumor progression. By employing an immunocompetent autochthonous glioblastoma mouse model, we will elucidate critical aspects of microglia-GB communication providing valuable insights into their reciprocal relationship.
DFG Programme
Priority Programmes
