A postdoctoral position is available immediately to investigate the function of epithelial cell apoptosis and removal of apoptotic epithelial cells by macrophage during pulmonary fibrosis. We and others have shown that epithelial cell apoptosis is a primary driver of fibrosis but the mechanism by which this occurs remains unknown. To address these deficits, we are pursuing a multifaceted approach using in vitro studies of primary murine and human alveolar epithelial cell and alveolar macrophages coupled with in vivo mouse models using novel transgenic mice. Although a loss of anti-fibrotic factors normally produced by healthy epithelial cells likely contributes to the initiation of scarring, our preliminary data lead us to pursue alternative pathways. Specifically, we have discovered that the injured epithelium expresses pro-fibrotic factors including CCL12, and we hypothesize that the secretion of these factors is required for fibrogenesis. We have found that phagocytosis of apoptotic bodies by macrophages can induce a profibrotic phenotype with increased production and activation of TGF and lung fibrosis. We are focused on a number of receptors necessary of uptake of the apoptotic bodies, including integrin beta3, along with the downstream signaling pathways leading to pro-fibrotic activation, such as FAK, Rac1 and MRTF. We are currently working to understand the intracellular mechanisms involved in this fibrotic response with a goal of identifying novel pathways for intervention. Research will involve molecular techniques, cell lines, primary cells, in vivo experiments in mice, and work with primary human cells and human tissue samples.
M.D. or Ph.D. with at least four years of dedicated lab experience required. Must be ambitious. Must have experience with standard cell and molecular biology techniques (cell culture, transfection, immunoblot, PCR, quantitative PCR, immunohistochemistry, flow cytometry, molecular cloning). Experience with transgenic mice is preferred. Expected to plan, conduct and analyze experiments independently.
Interested candidates should contact Dr.Kevin Kim, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, with current resume or CV and references . email@example.com
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