Pulmonary Arterial Hypertension (PAH) is a heterogeneous group of diseases with high mortality, difficult diagnosis, limited available treatment, and no cure. The Pulmonary Hypertension Breakthrough Initiative (PHBI) is dedicated to comprehensive biobanking of human lungs with PAH and controls, supported by a detailed clinical annotation of the accrued specimens. Having started in 2006, the PHBI successfully developed a novel and unique infrastructure, whose success relied on the active participation of a highly integrated network of university-based sites with extensive expertise in each of the spheres of competency: excellence in clinical care of PAH (including patient accruals), lung transplantation, pathology, genetics, genomics, and cell isolation. The goal of this application is to leverage these unparalled resources and unique expertise into an R24-supported initiative to direct the bank to accrue specimens of disease-specific groups, which will be highly integrated with pathologic, genetic, and genomic subphenotypes pertaining to not only lung and blood specimens, but now expanding to the failing PAH heart. This proposal will be highly synergistic with the presently supported initiatives by the NHLBI in the field. The flexibilty of our infrastructure and governance will allow us to be decidedly responsive and integrated with any future NHLBI initiatives. We propose that this unique infrastructure will serve the pressing roles of advancing the translation of key discoveries to the patients with PAH and to aid in new discoveries that will have a long lasting impact in the field. The following specific aims will be pursued: Specific Aims of the Proposal 1) To establish a comprehensive biorepository of the specimens from subjects with pulmonary arterial hypertension and failed donor controls. 2) To provide the infrastructure to support human tissue based research in PAH via integrated cores devoted to Administration, Tissue Handling and Pathology, Cell Line Development, and Genomic Characterization and Cataloging. 3) To develop and implement an interface for consultation of research design and analysis to enhance broader scientific investigation.