SUMMARY The Center for Lung Biology and Disease was established through a Phase I Centers of Biomedical Research Excellence (COBRE) award. Our Phase I proposal, aimed at providing Promising Junior Investigators (PJIs) an environment that maximizes their potential to contribute to advances in pulmonary disease research, launched 6 new scientists in independent research careers funded through 11 R-, 1F- and 1K-series NIH grants. This Phase II proposal will expand the tremendously successful programs established in Phase I, with an overarching goal of promoting research to unravel life- threatening respiratory diseases. Its thematic focus encompasses mechanistic studies of host responses to infectious and non-infectious stimuli. The leadership and mentoring teams are highly interactive and our four new PJIs are a dynamic group. In aim 1 of our strategy to launch these PJIs as independent researchers, we will maintain and expand an administrative structure that supports and fosters PJI progress toward scientific independence. This will be accomplished by coordinating activities of the individual projects and cores and fostering their collaborative engagement. We will also provide career and professional resources that together with a team of mentors with strong experience in NIH-funded lung biology, will foster PJI growth toward independent funding. In aim 2, we will enhance the research infrastructure at the LSU School of Veterinary Medicine and provide cutting-edge technologies for enhancing the competitiveness of our PJIs. Through partial funding from our Phase I award, we renovated and expanded our Animal Biosafety Level-2 (ABSL-2) footprint, and in this proposal, we will use institutional support to renovate and increase the footprint of our ABSL-3 facility 2-3-fold. Given the landscape of junior investigator research within our LSU Vet Med environment, where lung biology research emphasizes diseases induced by both infectious diseases and inhalation exposures, we have realized the need for providing one new resource – the Inhalation and Infection Core. The new core will assist investigators with animal infection and delivery of inhaled pollutants and/or therapeutic agents to support their mechanistic studies of respiratory diseases induced through both infectious and non-infectious stimuli. Finally, in aim 3, we will navigate pathways for sustained Center funding supported through the NIH P01 grant program, with the ultimate goal of positioning our growing depth of lung biology expertise to develop a Center of Excellence. The team assembled here has exceptional expertise in lung biology, outstanding leadership and mentoring experience, and a demonstrated history of productive collaboration. This COBRE program will provide novel insights into the pathogenesis of devastating lung diseases to guide improved strategies for treating and preventing these diseases in human populations.