Project Grant R01HL185414

Grant Award Summary

The National Heart, Lung, and Blood Institute (NHLBI) awarded a Project Grant totaling $712,630 to Trustees of Boston University, with an award date of August 1, 2026, and completion deadline of April 30, 2030, under the Cardiovascular Diseases Research program (CFDA 93.837). The project, titled "Functional Heterogeneity of Alveoli and the Early Response to Airborne Agents," will deliver fundamental research outputs advancing understanding of lung physiology and immune response mechanisms. The work utilizes an innovative intravital imaging platform called the Crystal Ribcage to enable real-time, high-resolution visualization of intact, ventilating lung tissue, producing the first single-particle resolution imaging of aerosol deposition within functional alveoli and discovery of a conserved mosaic pattern of anatomical organization.

The funded research will generate three primary deliverables: (1) detailed anatomical and physiological mapping of alveolar mosaicism, including spatial relationships between functionally distinct alveolar types and the first alveolus-level oxygen pressure mapping across multiple species including humans; (2) transcriptomic and spatial transcriptomics data characterizing gene expression differences in alveolar type 2 cells and macrophages from distinct alveolar compartments, alongside developmental evidence regarding preferential alveologenesis; and (3) mechanistic findings regarding how injurious aerosols differentially activate immune and injury responses based on alveolar location. These research outputs are expected to establish the biological significance of previously undescribed lung architecture and inform future therapeutic strategies for airborne agent exposure and respiratory disease.