Abnormalities of pathways of fibrinolysis have been implicated in the pathogenesis of pleural and acute lung injury (All). The objective of this PPG is to define novel mechanisms by which urokinase plasminogen activator (uPA), its receptor (uPAR), its inhibitor (plasminogen activator inhibitor-1, PAI-1) and its product (plasmin) influence the pathogenesis of All or pleural injury. To address this, the Project Leaders of this PPG will employ a number of various in vitro, in vivo and interventional methods, which require diverse proteins with highest purity and in large quantities. The Service Core is designed to provide this service. Further, all three projects of the PPG propose to use immunohistochemistry analysis to characterize the lung injury and expression of specific proteins/markers.relevant to lung injury and its repair. The Service Core provides the provision for such expertise. Thus, the aims of the Service Core are (i) to generate and provide various fibrinolytic proteins, their variants and derivatives, in sufficient quantities and purity to support the studies described in the individual projects comprising this PPG (ii) to provide support in pathology related services, including tissue preparation, thin sectioning, analysis of immunohistochemistry and in situ hybridization studies and morphometry. The Service Core uses proven technology for large-scale expression of recombinant fibrinolytic proteins and their variants. Efficient purification methods to purify recombinant proteins have been developed by either the project leaders or consultants of the PPG. A boardcertified Anatomic Pathologist with clinical and research expertise in thoracic pathology and application and interpretation of immunohistochemistry, in situ hybridization and morphometry provides expertise, accuracy and consistency in analysis of lung specimens. Overall, the Service Core provides a valuable support to all three projects of the PPG and maximizes the resources with substantial savings in cost.
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