MOLECULAR PATHOPHYSIOLOGY CORE

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CORE D: The overall goal of the core is to provide state of the art pathological and physiological expert support to basic science and clinical projects. Emphysema and chronic bronchitis involve structural alterations, which can be assessed morphologically. In fact, lung pathology is the gold standardfor the diagnosis of emphysema. Furthermore, we are uniquely fitted to integrate high quality morphological and physiological assessment of lung tissue, coupled with the interrogation of molecular and cellular pathological processes involved in COPD. Our core has developed state of the art lung microscopic imaging and computer-assisted morphometry, and small animal pulmonary function testing, allowing us to integrate structural abnormalities and their impact on lung physiology. The PI, Dr. Tuder, and Co-Pi and Mitzner have a long record of scientific collaboration, which will be instrumental for the success of the core. It is our goal to provide high quality tissue processing, accurate phenotypic characterization of alveolar and bronchiolar structure, and state-of-the art tools to investigate and validate potential markers of disease and pathogenetically relevant molecules that may have a role on the impact on parenchyma! lung injury, bronchiolar remodeling, andstructural alterations in COPD. We propose the following Strategies to accomplish these goals: 1) To assist the investigators in all projects in the experimental design aimed at investigation of alveolar and airway structure (Projects 1,2, and 4). 2) Perform pulmonary function testing in experimental models of emphysema (Projects 1,2, 3 and 4). 3) To perform immunohistochemical characterization of the pattern of lung distribution of markers and relevant proteins identified as important to the experiments outlined in Projects 1, 2, 3, 4, and 5. 4) To perform in situ hybridization aimed at the transcript localization in lungs (Projects 1, 2, 3, and 4). 5). To correlate the protein and transcriptional data with morphological alterations present at the light microscopic level (Projects 1-4).