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
