Project Summary/Abstract Idiopathic pulmonary fibrosis (IPF) and chronic lung allograft dysfunction (CLAD) are disorders characterized by the inexorable loss of lung function and death within 3-5 years of diagnosis. IPF and CLAD share features of relentless extracellular matrix (ECM) deposition and the lack of response to immunosuppressive therapy. Compelling preliminary evidence is presented in the 3 projects within this proposal that the progressive scarring inherent to both IPF and CLAD is the consequence of dysregulated crosstalk between the lung epithelium and the lung resident mesenchymal stromal cells. Although there are clear distinctions between mechanisms of IPF and CLAD, this common theme should be investigated for potential therapeutic benefit in each condition. Each of the 3 inter-related projects proposed in this application is strengthened by studies in human subjects including the collection of patient specimens. We propose a Human Core to facilitate the safe and efficient collection of research data and specimens from these human subjects. We will leverage access to the large UCLA lung transplant program to supply high-quality human samples for the 3 program projects in this application. Specifically, we will recruit and enroll 300 subjects listed for lung transplant, for any indication, to participate in a post-transplant registry and bronchoscopy sample study proposed in Project 3. Among these 300 subjects, those with a diagnosis of IPF will be recruited to also provide their explanted IPF lung tissues for Projects 1 and 2. All subjects will be entered into a registry and the samples will be linked to this robust longitudinal database for clinical phenotyping. The Human Core comprises an experienced team of investigators, clinical research staff and laboratory personnel who will support human subject research and biological sample collection and processing for each of the 3 projects. This team has successful collaboration across multiple projects during the past 5 years. Therefore, the combination of a high volume lung transplant program, investigators' expertise, and an established infrastructure for human subject research and sample collection, collectively amount to a one-of-a-kind resource to study IPF and CLAD.