Gliomas are aggressive brain tumors marked by extreme cellular and metabolic heterogeneity that drives therapy resistance and poor outcomes. Building on findings from Dr. Nathalie Agar’s laboratory at Brigham and Women’s Hospital demonstrating distinct metabolic signatures across tumor regions, this project aims to develop novel methods to spatially quantify metabolites, drugs, and biomarkers in patient brain cancer tissue. We will integrate spatial transcriptomics, cyclic immunofluorescence, and MALDI mass spectrometry imaging (MALDI-MSI) to map tumor cell states, immune populations, and key metabolic pathways at high spatial resolution. By quantitatively co-registering endogenous metabolites and therapeutic drug distributions with spatial gene expression and cellular neighborhoods, we will define metabolic and pharmacologic heterogeneity across glioma grades and IDH status. This integrated spatial framework will enable direct assessment of drug penetration and metabolic rewiring in situ, supporting biomarker discovery, derisking of therapeutic strategies, and the development of more effective, precision-guided treatments for patients.
Northeastern University
