Cell Isolation and Organ Function Core

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The central goals of the CardioPulmonary Vascular Biology (CPVB) Center for Biomedical Research Excellence (COBRE) are to understand basic mechanisms of vascular disease pathogenesis and to translate these findings into treatments for heart and lung diseases. Vascular injury, repair, and remodeling are critical to the pathogenesis of the conditions studied in Phase II projects--bronchopulmonary dysplasia (BPD), atherosclerosis, idiopathic pulmonary fibrosis (IPF), pulmonary hypertension, and acute respiratory distress syndrome (ARDS). Cardiac development and remodeling in response to injury similarly include both adaptive and maladaptive responses. Dysfunction of angiogenesis, the reparative response of the endothelium to injury, and aberrant vascular remodeling have been proposed to occur in ARDS, BPD, IPF and other heart and lung conditions. In addition, some congenital heart defects result from mutations in transcription factors that regulate cardiomyocyte and endothelial cell (EC) function in development. Thus, an increased understanding of the mechanisms regulating the adaptation of the vasculature to injury and repair may lead to unique approaches to interrupt disease progression or to promote or enhance cardiopulmonary vascular repair. During Phase I the Cell/Organ Core developed centralized systems for cell isolations and organ function measurements and provided reproducible and accurate data for COBRE Projects. Additional services underway to enhance the Cell/Organ Core capabilities for the vascular biologists in Rhode Island and Phase II investigators are expansion of i) type of cell isolations; ii) immunohistochemical analyses; iii) EC function of primary isolates; iv) laser Doppler imaging; and v) in vivo angiogenesis. The Core will offer consultation on experimental design, provide cutting edge technological approaches, generate and analyze data, and serve as a resource for CPVB COBRE investigators and others in Rhode Island. The Core will also develop a business plan for financial stability of existing services and identify novel business or collaborative opportunities to ensure sustainability of the CPVB core. The overall goal of the Cell/Organ Core is to facilitate the scientific objectives and technical repertoire of the Project and Pilot Investigators by the following specific aims. (1) Enhance the productivity of CPVB COBRE research projects by offering reproducible, economical, and high quality i) cell isolation, propagation, phenotypic characterization and functional assessment ii) assessment of heart, lung, vessel structure and function and angiogenesis, and (iii) transient gene manipulation in vivo. (2) Acquire, establish, and disseminate technologies and instrumentation to provide state of the art research tools for vascular biology research in Rhode Island. (3) Establish processes and procedures that support the sustainability of the Cell/Organ Core. The CPVB COBRE Cell/Organ Core will support vascular biology research, including new investigators, projects, technical approaches and ideas that enhance the impact of research in Rhode Island.