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P.I.:<\/strong> William Altemeier, MD<\/a> Cystic Fibrosis (CF) is characterized by persistent lung neutrophilic inflammation, which contributes to progressive lung injury. Significant research effort has focused on epithelial and myeloid mechanisms of airway inflammation in CF; however, little is known about the role of the lung microvasculature, the site of initial neutrophil tissue migration. Pulmonary capillaries consist of endothelial cells and peri-vascular mesenchymal cells or pericytes. Both cell types are critical in initiating neutrophil sequestration and migration. Endothelial cells express functional CFTR; whereas, pericyte expression is unknown. We present new data that pericytes express CFTR and hypothesize that abnormal CFTR expression in lung endothelial cells and\/or pericytes results in elevated expression of neutrophil adhesion molecules and neutrophil-targeted chemokines. To test this hypothesis, basal activation state and response to bacterial stimulation will be quantified in mouse lung pericytes and endothelial cells, expressing wildtype-CFTR, \u0394F508-CFTR, or no CFTR. Subsequent experiments will evaluate the role of aberrant CFTR expression in either pericytes or endothelial cells, using a microfluidic pericyte-endothelial cell co-culture system to assess neutrophil adhesion. In the final aim, biomarkers of endothelial activation will be measured in CF subjects and subjects with normal CFTR genotype. The effect of disease-modifying therapy on biomarkers of endothelial activation will be assessed in serum collected from \u0394F508 CF patients before and after initiating therapy with Ivacaftor\/Lumacaftor. At the conclusion of this study, knowledge regarding the role of lung microvasculature on lung neutrophilic inflammation will provide the basis for consideration of subsequent studies, assessing the utility of endothelial activation inhibitors in CF.[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section]<\/p>\n","protected":false},"excerpt":{"rendered":" Pilot 12: Identification of Biomarkers for Cystic Fibrosis Associated Nephrotoxicity<\/p>\n P.I.: \tNeal Paragas, PhD P.I.: Steven Kahn, MB, ChB<\/a>
\nAssociate Professor, Pulmonary and Critical Care Medicine <\/p>\n
\n\tResearch Assistant Professor,
\n\tMedicine (Nephrology)<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"
Professor of Medicine
Metabolism, Endocrinology and Nutrition<\/p>