Federal Grant Award Summary

The National Heart, Lung, and Blood Institute (NHLBI) awarded the Regents of the University of Michigan a Project Grant totaling $724,200 under the Cardiovascular Diseases Research program (CFDA 93.837) effective July 10, 2026, with completion targeted for April 30, 2030. The award funds research titled "Endothelial Fate Switches and Function via Matrix Control of Adherens Junctions," which investigates the mechanisms by which fibrotic matrix remodeling dysregulates endothelial cell function and contributes to pathological fibrosis in conditions such as pulmonary fibrosis, cirrhosis, and solid cancers.

The research deliverables include mechanistic studies using mouse models and a human microphysiological system (MPS) that simulates arteriole and venule-scale microvessels to elucidate how fibrotic physical cues activate endothelial cells, drive endothelial-mesenchymal transition (EndMT), and promote aberrant single endothelial cell invasion into the stromal matrix. The project will characterize the destabilization of endothelial adherens junctions as a critical gating mechanism for this pathological process and identify how single endothelial cells maintain adherence to fibrotic matrix while reinforcing fibrogenesis through signaling interactions with stromal cells. These findings are expected to provide novel therapeutic targets for dysregulated fibrosis by identifying cellular mechanisms beyond myofibroblast differentiation that drive excessive extracellular matrix deposition and tissue remodeling.