Surgical stress- and therapy induced transcriptional reprogramming of the spatial landscape in glioblastoma

• Applicant: Professor Dr. Dieter-Henrik Heiland
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 527529530

Glioblastomas are the most common malignant disease of the central nervous system. In the last decade, the majority of all clinical trials failed to achieve their targeted endpoint despite promising preclinical results. The mechanisms of resistance and remodeling in relapse are poorly understood to date. Recent studies using high-throughput techniques such as multi-omic or single-cell analysis have shown only marginal changes in the tumor. My research group is intensively focused on spatial changes at the cellular, metabolic and transcriptional level to understand the complex interactions of the tumor. Considering the spatial relationships, novel insights into the assembly of cellular interactions emerge. The proposed project plans to investigate the alteration of the spatial transcriptional architecture of glioblastomas under intrinsic and extrinsic influences. By applying spatially resolved transcriptome analysis we aim to characterize glioblastomas under various therapies. This will outline not only therapy related effects, but also the changes due to surgical intervention. We hypothesize that tumor resection and adjacent tissue injury play a significant role in the immunological reformation of the tumor microenvironment. A holistic approach using artificial intelligence should allow us to consider the gained knowledge integratively rather than isolated and additionally provide the possibility to incorporate a wide variety of clinical parameters. The goal is to model changes of the tumor under therapy and to predict potential response. Our project is expected to provide directional insights that may help to personalize future therapy planning and provide new clues to therapeutic targets.

• DFG Programme: Research Grants