Neurosurgical Research at the University Hospital Munich

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Project description:

Histone modifications are diagnostically relevant in cancer and are closely related to metabolism, which is very different in tumor tissue. Understanding the spatial distribution of these modifications in situ is critical for deciphering disease biology. However, conventional methods like immunohistochemistry (IHC) are severely limited in throughput, as they can only detect a few markers simultaneously due to spectral overlap and a scarcity of suitable, specific antibodies. This project will overcome this bottleneck by establishing a new, high-throughput technology. Leveraging the Imhof Lab’s expertise in mass spectrometry-based proteomics and histone modification analysis, we propose a novel method using Matrix-Assisted Laser Desorption/Ionization (MALDI) imaging mass spectrometry. Our approach employs selective binders tagged with UV-cleavable peptides of different masses. Upon laser irradiation, these lowmolecular-weight tags are released and detected, enabling the parallel analysis of up to 200 histone modifications and providing a much deeper, spatially resolved coverage of the chromatin landscape. Crucially, this method can also be integrated with the simultaneous spatial analysis of metabolites on the same tissue section. This unique multi-omics capability will enable a direct investigation into how metabolic dysregulation directly shapes the epigenetic landscape within different regions of a tumor. The method will be validated using various tumor tissues from collaborators at the LMU clinic, with the ultimate goal of advancing personalized cancer diagnostics.