[et_pb_section fullwidth=”on” specialty=”off”][et_pb_fullwidth_slider admin_label=”Fullwidth Slider” show_arrows=”on” show_pagination=”on” auto=”off” parallax=”off” parallax_method=”off” module_id=”interior”][et_pb_slide background_image=”https:\/\/depts.washington.edu\/cfrtc\/wp-content\/uploads\/2014\/12\/microscope11.jpg” background_color=”#ffffff” alignment=”center” background_layout=”dark” \/][\/et_pb_fullwidth_slider][\/et_pb_section][et_pb_section][et_pb_row][et_pb_column type=”1_4″][et_pb_sidebar admin_label=”Pilots Sidebar” orientation=”left” area=”et_pb_widget_area_7″ background_layout=”light” \/][\/et_pb_column][et_pb_column type=”3_4″][et_pb_text admin_label=”Text” background_layout=”light” text_orientation=”left”]<\/p>\n

The NLRP3 Inflammasome in The Cystic Fibrosis Lung<\/h1>\n

P.I.:<\/strong>\u00a0Andrew Graustein
\nActing Instructor,
\nPulmonary and Critical Care<\/p>\n

Cystic fibrosis (CF) is characterized by recurrent pulmonary infection and inflammation that leads to progressive decline in lung function. Identifying which immune responses are beneficial versus pathologic is critical for the development of treatment strategies. The NLRP3 inflammasome responds to intracellular stress conditions, including those caused by Pseudomonas aeruginosa <\/em>in the CF lung, by producing a caspase-1-mediated inflammatory response. In mice with CF, while NLRP3 helps to clear infection, the NLRP3-mediated inflammatory response is dysregulated and leads to lung pathology. We propose to study the relationship between NLRP3 and CF in humans. For Aim 1, we will use a molecular approach by generating gene knockouts of NLRP3<\/em>, CFTR<\/em>, or the combination of both in macrophage cell lines and induced pluripotent stem cells. We hypothesize that the absence of CFTR <\/em>will exacerbate NLRP3-mediated inflammation and that the absence of NLRP3 <\/em>will limit Pseudomonas<\/em>-induced inflammation. For Aim 2, we will use a genetic approach and screen a local healthy cohort for NRLP3 <\/em>genetic variants that are associated with gene expression or NRLP3-mediated inflammatory responses. We will examine genetic variants from a cohort of children with CF for association with rate of lung function decline or time to colonization with P. aeruginosa<\/em>. We hypothesize that variants in the NLRP3 <\/em>gene region will alter NRLP3 activation and that these variants will influence CF-related outcomes. The proposed studies will improve our mechanistic insight into pathologic inflammation in the CF lung and will provide evidence for the targeting of host directed therapeutics in patients with CF.<\/p>\n

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\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\n\t\t\t<\/div> The NLRP3 Inflammasome in The Cystic Fibrosis Lung P.I.:\u00a0Andrew Graustein Acting Instructor, Pulmonary and Critical Care Cystic fibrosis (CF) is characterized by recurrent pulmonary infection and inflammation that leads to progressive decline in lung function. Identifying which immune responses are beneficial versus pathologic is critical for the development of treatment strategies. The NLRP3 inflammasome […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"

P.I.: Steven Kahn, MB, ChB<\/a>
Professor of Medicine
Metabolism, Endocrinology and Nutrition<\/p>

Kristina Utzschneider, MD<\/a>
Associate Professor of Medicine
Metabolism, Endocrinology and Nutrition<\/p>

With the increased life expectancy of patients with cystic fibrosis (CF), other co-morbidities have become apparent in these patients. One of these is abnormal glucose metabolism, where CF-related diabetes (CFRD) is common. More recently, another abnormality of glucose metabolism has been recognized; namely late hypoglycemia following oral glucose loading. In this study, we propose to test the hypothesis that the post-glucose load hypoglycemia observed in patients with CF results from a deficient counterregulatory hormone response and\/or an insulin response that is exaggerated and delayed. This increased insulin response could be the result of an exaggerated incretin hormone response or altered gastric emptying. To address this hypothesis, we will perform a 3-hour oral glucose tolerance test during which we will measure counterregulatory, islet and incretin hormone responses and determine the rate of gastric emptying using acetaminophen. To determine whether patients with CF and late hypoglycemia also have episodes of hypoglycemia during daily living that includes mixed meals, we will use a continuous glucose monitoring system (CGMS) to examine 24-hour glucose profiles for 3 days. All these measures will be compared between patients with CF who develop late hypoglycemia, CF patients who do not develop hypoglycemia, and age and body mass index-matched healthy controls. The findings from this study will provide important new information regarding the mechanism(s) responsible for the late hypoglycemia observed in patients with CF and the data could be used as the basis for future grant applications. The ultimate goal is to gain insight into the condition of late hypoglycemia in order to better manage patients with CF.<\/p>","_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\/1330"}],"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=1330"}],"version-history":[{"count":1,"href":"https:\/\/depts.washington.edu\/cfrtc\/wp-json\/wp\/v2\/posts\/1330\/revisions"}],"predecessor-version":[{"id":1331,"href":"https:\/\/depts.washington.edu\/cfrtc\/wp-json\/wp\/v2\/posts\/1330\/revisions\/1331"}],"wp:attachment":[{"href":"https:\/\/depts.washington.edu\/cfrtc\/wp-json\/wp\/v2\/media?parent=1330"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/depts.washington.edu\/cfrtc\/wp-json\/wp\/v2\/categories?post=1330"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/depts.washington.edu\/cfrtc\/wp-json\/wp\/v2\/tags?post=1330"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}