WILLIAM HARDIE

..Finally, we will present data demonstrating a minimal contribution of epithelial-mesenchymal transition in the development of fibrotic lesions in the transforming growth factor-alpha transgenic model of lung fibrosis...

..These findings demonstrate that MEK inhibition prevents progression of established fibrosis in the TGF-α model, and provides proof of concept of targeting the MEK pathway in fibrotic lung disease...

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..These studies support a role for epithelial cell-derived TGF-alpha in the regulation of processes that alter the airway and vascular architecture and function...

..Induction of pulmonary fibrosis by TGF-alpha was independent of inflammation or early activation of TGF-beta...

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..Pathological changes in TGF-alpha-overexpressing mice bore similarities to premature infants born in the saccular phase who develop BPD, including remodeling of the distal lung septae and arteries...

..Abnormalities in surfactant function and decreased surfactant level in the airways may contribute to the pathophysiology induced by TGF-alpha in both the developing and adult lung...

..This study demonstrates that EGFR signaling, especially in the airway epithelium, plays an important role in mediating AHR and remodeling in a chronic allergic asthma model...

..In the TGF-alpha transgenic mouse model, TGF-alpha protects against nickel-induced acute lung injury, at least in part, by attenuating the inflammatory response, reducing pulmonary edema, and preserving levels of SP-B...

..This provides a unique model to study the processes causing pulmonary fibrosis and ASM thickening without the complicating effects of inflammation...

..Thus, the functional genomic approaches of large gene set expression (complementary DNA microarray) and genome-wide analyses continue to provide novel insights into the genetic susceptibility of lung injury...

..Reductions in VEGF may contribute to the pathogenesis of pulmonary vascular disease in TGF-alpha mice...

..These data show that PI3K is activated in TGFalpha/EGFR-mediated pulmonary fibrosis and support further studies to determine the role of PI3K activation in human lung fibrotic disease, which could be amenable to targeted therapy...

..Previously, we reported that acrolein levels found in COPD sputum could activate matrix metalloproteinase-9 (MMP9)...

..Augmentation of hMMP9 activity, in turn, could contribute to persistent excessive mucin production...

..These data demonstrate most children are able to perform acceptable/repeatable spirometry with their first effort based on revised ATS/ERS criteria...

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..The experiments proposed will permit the P.I. to develop an independent line of research in a division dedicated to understanding the basic pathobiology of various lung diseases. ..

..Completion of the proposed studies will determine a role of EGFR in lung fibrosis and suggest therapeutic targets to alter the course of human lung fibrosis. ..

..Completion of the proposed studies will determine a role of EGFR in lung fibrosis and suggest therapeutic targets to alter the course of human lung fibrosis. ..

..Completion of the proposed studies will determine a role of EGFR in lung fibrosis and suggest therapeutic targets to alter the course of human lung fibrosis. ..