ABSTRACT/SUMMARY Leveraging the technologies and infrastructure in our previous LungMAP phases, we will construct a multi-scale map of developing acinar and alveolar structures during normal childhood and in the setting of childhood interstitial lung disease (chILD) characterized by aberrant lung morphogenesis. Linked to gene variants, chILD provides a unique opportunity to understand key genetic pathways and cellular interactions of human acinar and alveolar development, in turn informing injury-repair associated with lung diseases throughout the lifespan. Working in a collaborative LungMAP3 consortium, including other Research Centers, the Data Coordinating Center (DCC), the Human Tissue Core (HTC), our LungMAP3 project will use single-cell and spatial multiomics, high-resolution confocal and electron microscopy, patient-derived iPSCs, and bioinformatics including AI tools to define, model, and predict normal and diseased lung development. The resulting mechanistic insights and enabling technologies will be disseminated to the entire lung community via disease atlases and web portals, as we have done during LungMAP1 and 2, to accelerate lung biology discoveries and disease therapies.

PROJECT NARRATIVE Our Research Center will leverage our extensive lung tissue biobank and expertise in multi-omics, induced pluripotent stem cells (iPSC) differentiation, and bioinformatics to construct a multi-scale map of the developing acinar and alveolar structures for the normal human lung and those with childhood interstitial lung disease (chILD). We will establish new technologies, experimental protocols, and computational approaches to support the pulmonary research community and develop AI-powered analysis of complex multi-omic data to identify gene regulatory networks underlying normal lung formation and disease-related tissue remodeling. We will also generate patient-derived iPSCs to model and interrogate disease pathogenesis. LungMAP 2 - Project Narrative-v7