SUMMARY Single-cell/genomic technologies offer unprecedented opportunities to examine the cellular and molecular mechanisms of disease initiation and progression, predict disease development and progression, and examine how genetic and environmental risk factors mediate disease risk. Each of the four projects in this Program leverages state-of-the-art genomic approaches aligned with the Project specific aims, which will be coordinated and executed in close collaboration with the Genomics Core. This cross-institutional core will leverage expertise in wet-lab single-cell methods, genetics, single-cell transcriptomics, epigenomic analyses, and lung biology to provide integrated support for each Project. The Genomics Core will support all aspects of the generation, storage, and computational analysis of single-cell and other genomic data through the studies in Projects 1-4. The Genomics Core has four specific aims in support of its role: 1) to establish and implement best-practices for generation of high-quality genomic data, 2) to facilitate secure storage and transfer of genomic data across all Projects, 3) to provide best-practice-grounded analysis of transcriptomic and multiomic data generated in Projects 1-4, and 4) to facilitate sharing and dissemination of genomic data and analysis code. Through these aims, the Genomics Core will establish Standard Operating Procedures for each data modality that will be generated across the Projects, serve as the genomic data storage/transfer hub in support of each project, establish and deploy best-practice-based pipelines for key functions, and optimize purpose- built analytic strategies for the specific research questions in the Projects. In addition, the Core will fulfill our commitment to rapid and transparent data sharing by using approved portals to disseminate genomic data to the research community.