Pathophysiology Core

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The primary objective of the Pathology and Imaging Core is to provide accurate phenotypic characterization of pulmonary vascular remodeling, document activation of complement, assess inflammation, and isolate mRNA and proteins, in diseased IPAH human lungs and relevant models of PH. To accomplish these goals, we will perform 8 tasks based on specific methodologies, aimed at integrating high quality tissue processing, immunohistochemistry, and stereology with high throughput imaging approaches and laser capture microdissection for all 4 projects in this PPG. Aim 1: To provide qualitative and quantitative assessment of pulmonary vascular remodeling in lungs of humans, steers and newborn calves, rats, and mice in Projects 1-4. We propose 4 specific tasks to support this specific aim, which include: planning of experiments (task 1), collection, processing, and phenotyping experimental lungs (task 2), morphology and stereology of pulmonary vascular remodeling (task 4), and integration of morphological data with specific project goals and aims (task 8). Aim 2: To determine expression patterns and abundance of candidate molecules investigated in experimental lungs. We propose 5 specific tasks to support this specific aim, which include planning of experiments (task 1), tissue processing (task 2), morphology and stereology (task 3), laser capture microdissection (LCM; task 7), and integration of morphological data with project goals and aims (task 8). Aim 3: Specific Aim 3: To obtain high quality mRNA and protein for transcriptomic and proteomic studies from specific pulmonary vascular structures and lesions from animals manipulated in Projects 1-4. We propose 5 specific tasks to support this specific aim, which include planning of experiments (task 1), tissue processing (task 2), LCM (task 7), and integration of morphological data with specific project goals and aims (task 8). Aim 4: To translate the key expression findings in Specific Aim 2 to human control and PAH lungs. We propose six specific tasks to support the specific aim, which include planning of experiments (task1), tissue processing (task 2), human tissue studies (task 3), morphology and stereology (task 4), LCM (task 7), and integration of morphological data with specific project goals and aims (task 8). Foremost in accomplishing these goals is the scientific expertise within the leadership of the core. The Pathology and Imaging Core is led by of Drs. Rubin M. Tuder, an experimental and practicing pulmonary pathologist with major expertise in pathology and pathobiology of pulmonary hypertension, with the support of Dr. Raphe Nemenoff, an experienced investigator in the cancer field with expertise in multiprobe immune imaging targeting the immune system and complement. The novelty of the Pathology and Imaging Core lies on the unique resources, unmatched expertise, and overall experimental breadth, allowing for the integration and human translation pertaining to all four projects.