While the poor prognosis of glioblastoma arises from the invasion of a subset of tumor cells,
little is known of the metabolic alterations within these cells that fuel invasion. We integrated
spatially addressable hydrogel biomaterial platforms, patient site-directed biopsies, and
multi-omics analyses to define metabolic drivers of invasive glioblastoma cells.
Metabolomics and lipidomics revealed elevations in the redox buffers cystathionine,
hexosylceramides, and glucosyl ceramides in the invasive front of both hydrogel-cultured …

METHODS: We integrated spatially addressable hydrogel biomaterial platforms, patient site-
directed biopsies, and multi-omics analyses to define metabolic drivers of invasive
glioblastoma cells. A CRISPR metabolic gene screen was utilized to identify metabolic
genes crucial for GBM invasion. We further targeted an identified hit from our high-
throughput screens by utilizing a sgRNA to generate a knockdown cell line and assessing
invasion in vitro and in vivo in a patient-derived xenograft orthotopic mouse model …