Research Description

Research Center for Spatiotemporal Lung Imaging And Omics

Lung development is a complex process that is spatiotemporally coordinated by a myriad of molecular events occurring in the different microenvironment and cell types composing in the pulmonary tissue. In human this process is continued postnatally with the alveologenesis occurring during the first few months to year of life. Alveologenesis is a dynamic, coordinated process that requires the accurate spatial and temporal integration of signals to develop the intricate alveolar structure. While important progress has been made, significant knowledge gaps remain in our understanding of the molecular mechanisms driving postnatal development. For this reason, our NHLBI established Research Centers (RCs) to create a spatiotemporal molecular atlas of the developing lung (LUNGMAP) focused from birth up to early childhood (~8 years). In the first phase of LungMAP, our RC developed resources that enabled a much more detailed understanding of normal lung development up to early childhood. In LUNGMAP Phase 2, we will apply our successful approaches and our newest technologies to extend analysis of lung development into early adulthood as well as human disease; focusing on bronchopulmonary dysplasia (BPD), the most common morbidity of preterm infants which is characterized by delayed or deficient lung maturation. Within the lung, the relationship between space, anatomy, and function is fundamental. Therefore, our approach includes new unbiased 3D quantitative imaging approaches implemented with high spatial resolution, as well as cell-specific omics: proteomics, lipidomics, and metabolomics. The integration of these complementary data collection methods facilitates the establishment of a cell-specific spatial atlas with an incredible breadth of molecular profiles across the developing lung in normal and disease states.

Specifically, we will accomplish our goal of an integrated molecular atlas of lung development through the following aims: (1) Spatial imaging for a molecular atlas of the human lung in normal and diseased states, (2) Cell-specific omics for a molecular atlas of the human lung in normal and diseased states, and (3) Managing data to facilitate collaboration and data integration.

Overall, these aims will create unprecedented multi-scale browsable quantitative three-dimensional “Maps” of proteins, lipids, and metabolites across the developing lung, providing for many novel insights toward understanding both normal human lung biology and disease pathogenesis.