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Macrophage and Dendritic Cell Pathways in Cystic Fibrosis<\/p>\n<\/h2>\n
P.I.: Lev Becker, PhD<\/a><\/strong> Project Period: 2010 – 2013<\/p>\n Abstract: The clinical hallmark of cystic fibrosis (CF) is greatly increased susceptibility to infection with pathogenic bacteria like P. aeruginosa. Cystic fibrosis is primarily a disorder of electrolyte transport that results due to mutations in the CF transmembrane conductance regulator (CFTR) gene. One major unresolved issue in CF pathogenesis is how chloride dysregulation leads to the observed clinical manifestations. While it is well established that the lung epithelium contributes to this process, relatively little is known about the role of CFTR deficient alveolar macrophages (M\u03a6) and dendritic cells (DC).<\/p>\n We hypothesize that CFTR deficiency in M\u03a6s and DCs influences their immune function thereby contributing to sustained bacterial infection and inflammation in CF. We intend to approach this unresolved issue from two angles. First, we will use a proteomics-based approach to identify plasma membrane-associated markers of differentially activated M\u03a6s and DCs in humans and then use these markers to phenotype macrophages in normal and CF lungs. Second, by interrogating the plasma membrane proteomes of monocyte-derived M\u03a6s and DCs from CF patients we will simultaneously address the effect of CFTR deficiency on cell differentiation and\/or activation pathways and identify phenotype-specific effects of CFTR deficiency on protein expression. The functional significance of any CFTR-dependent changes in protein expression in M\u03a6s\/DCs will be determined by elucidating their effect on neutrophil function.<\/p>\n Collectively, the proposed studies should provide important insights into how CF monocyte derived immune cells contribute to the pathogenesis of cystic fibrosis.[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section]<\/p>\n","protected":false},"excerpt":{"rendered":" Pilot 5: Role of Islet Amyloid and Il-1\u03b2 Signaling in \u03b2-cell Loss in Cystic Fibrosis-Related Diabetes<\/p>\n P.I.: Rebecca Hull, PhD Srinath Sanda, MD This proposal seeks to determine the role of IL\u03b2 in the pathogenesis of cystic fibrosis related diabetes (CFRD). CFRD is a unique form of diabetes and new treatments are needed to improve the morbidity and mortality of cystic fibrosis patients. Therefore the goals of this grant proposal are directly relevant to the mission of the National Institute of Diabetes, Digestive, and Kidney Diseases.<\/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":"","_et_gb_content_width":"","_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":"","_links_to":"","_links_to_target":""},"categories":[12],"tags":[],"_links":{"self":[{"href":"https:\/\/depts.washington.edu\/cfrtc\/wp-json\/wp\/v2\/posts\/541"}],"collection":[{"href":"https:\/\/depts.washington.edu\/cfrtc\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/depts.washington.edu\/cfrtc\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/depts.washington.edu\/cfrtc\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/depts.washington.edu\/cfrtc\/wp-json\/wp\/v2\/comments?post=541"}],"version-history":[{"count":21,"href":"https:\/\/depts.washington.edu\/cfrtc\/wp-json\/wp\/v2\/posts\/541\/revisions"}],"predecessor-version":[{"id":3301,"href":"https:\/\/depts.washington.edu\/cfrtc\/wp-json\/wp\/v2\/posts\/541\/revisions\/3301"}],"wp:attachment":[{"href":"https:\/\/depts.washington.edu\/cfrtc\/wp-json\/wp\/v2\/media?parent=541"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/depts.washington.edu\/cfrtc\/wp-json\/wp\/v2\/categories?post=541"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/depts.washington.edu\/cfrtc\/wp-json\/wp\/v2\/tags?post=541"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
\nAssistant Professor
\nDepartment of Pediatrics
\nUniversity of Chicago
\nP30 CFRTC Publications<\/a><\/p>\n
\nResearch Assistant Professor of Medicine
\nMetabolism, Endocrinology and Nutrition<\/p>\n
\nAssociate Professor, Pediatrics
\nUniversity of California at San Francisco<\/p>\n