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Engineered GLICO model to study mechanometabolic dynamics at the GBM-brain interface

Award Number: R01CA308327
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/13/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2031

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Engineered GLICO model to study mechanometabolic dynamics at the GBM-brain interface - Glioblastoma (GBM) remains a uniformly lethal brain tumor despite aggressive surgical and adjuvant therapies, primarily due to its remarkable ability to adapt to microenvironmental stress. As GBM grows and remodels its surroundings, solid stress and tissue deformation alter extracellular matrix organization, oxygen and nutrient availability, and cellular mechanotransduction, generating spatially distinct metabolic niches that promote invasion or dormancy. Surgical resection further reshapes this landscape by inducing a wound-healing response—glial scar formation, astrocyte contraction, and ECM stiffening—that metabolically reactivates residual tumor cells and fuels recurrence. This mechanics-driven metabolic plasticity represents a fundamental yet poorly understood driver of GBM progression and therapy resistance. The goal of this project is to establish an engineered glioblastoma cerebral organoid (GLICO) model system that enables spatially controlled manipulation of tissue mechanics to uncover how the mechanical microenvironment at the GBM–brain interface shapes metabolic heterogeneity and drives invasion and recurrence. To achieve this, we will integrate tunable organoid compression platforms, a resected GLICO decompression model, and spatiomics with spatiometabolic imaging to decode the interplay between mechanical stress and metabolic remodeling. This approach is grounded in robust preliminary data demonstrating the emergence of mechanometabolic hotspots within the GLICO model. Spatial transcriptomics (DBiT-seq) and optical metabolic imaging (OMI) revealed coordinated activation of mechanotransduction and metabolic pathways along the invasive front, while compression and resection GLICO models confirmed the reproducibility of these mechanically induced responses. Building on these findings, we will (1) spatially map metabolic and mechanical remodeling at the GBM–brain interface before and after resection, (2) manipulate tissue mechanics in engineered GLICO systems to define their impact on GBM mechanometabolic dynamics, and (3) establish a controlled GLICO resection model to examine how post- surgical remodeling can be therapeutically targeted to prevent recurrence. Together, these advances will create a powerful human-relevant platform to decode the mechanometabolic mecanism of GBM invasion and recurrence and to identify actionable therapeutic vulnerabilities that arise from the intersection of tissue mechanics and metabolism.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $662,962 )
2026	2026	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Cancer Biology Research	000	1	8/13/2026	NEW	$662,962
														Subtotal = $662,962

Grand Total All Awards = $662,962

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Engineered GLICO model to study mechanometabolic dynamics at the GBM-brain interface

Award Number: R01CA308327

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/13/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2031

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