Project Grant R01HL178478

Grant Award Summary

The National Heart, Lung, and Blood Institute (NHLBI) awarded a Project Grant of $770,247 to Massachusetts General Hospital (The General Hospital Corporation) on July 5, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837). The award funds mechanistic research investigating the cellular and molecular basis of airway metaplastic responses, with anticipated completion by February 28, 2030. The research will establish the propensity of anatomically regionalized basal stem cell populations in mouse and human airways to undergo squamous or mucous metaplasia, examining the roles of stem cell heterogeneity, Yes-associated protein (YAP) signaling, and epidermal growth factor receptor (EGFR) signaling pathways. The work will assess regional differences in dorsal hillock-located basal stem cells, proximal pseudostratified basal stem cells, and distal pseudostratified basal stem cells across multiple anatomical compartments.

The deliverables include comparative studies of stem cell populations across anatomical regions, characterization of YAP overexpression effects on metaplasia pathways, and molecular profiling via ATAC-seq and RNA sequencing to elucidate mechanistic differences between squamous and mucous metaplasia in common pathologic signaling contexts. These research products will advance understanding of why both forms of epithelial metaplasia occur simultaneously in airway disease despite exposure to identical signaling environments, with implications for respiratory disease pathogenesis and treatment.