Combining large-scale electrophysiology, retrograde tracing, and spatial transcriptomics to probe neuron-tumor networks

• Applicant: Dr. Varun Venkataramani
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 569442277

The project aims to investigate the complex interactions between glioblastoma (GB) tumor cells and neuronal networks, with the goal of developing new therapeutic approaches. Glioblastomas are the most prevalent and aggressive primary brain tumors in adults, with poor prognosis despite comprehensive treatment. Recent research has shown that GB cells can form functional connections with neurons, which promotes tumor growth and invasiveness. This tumor-neuron communication likely contributes to therapy resistance. The research team plans to combine advanced technologies: Retrograde tracing using rabies viruses to map neuronal connections with tumor cells; High-density microelectrode arrays (HD-MEAs) for capturing neuronal activity patterns; Spatially resolved transcriptomics for single-cell gene expression analysis; Defined human cell culture models using induced neurons. The main objectives of the project are: To track and characterize the formation and dynamics of tumor-neuron connections in defined human cell culture models; To identify molecular signatures of tumor-induced pathophysiological alterations by integrating electrophysiological and transcriptomic data; To screen FDA-approved drugs to assess their effects on tumor-neuron networks and use machine learning to predict new compounds; To validate the most promising targets in patient-derived xenograft models and combine them with standard-of-care therapies. The project combines the expertise of two research groups: the team at Heidelberg University Hospital with extensive experience in neuro-oncology and tumor-neuron interactions, and the team at ETH Zurich with specialized knowledge in neuronal network electrophysiology and human cellular models. The expected outcomes include: A better understanding of the molecular mechanisms underlying tumor-neuron communication; Identification of new therapeutic targets; Development of multi-modal methods for functional and genomic characterization of tumor micro-environments; Validated targets with the potential to be translated into clinical trials. This interdisciplinary project could lead to new treatment strategies for glioblastomas by targeting the previously poorly understood neuron-tumor networks, potentially improving patient outcomes.

• DFG Programme: Research Grants
• International Connection: Switzerland
• Partner Organisation: Schweizerischer Nationalfonds (SNF)
• Cooperation Partner: Dr. Manuel Schröter