{"id":548,"date":"2015-05-21T17:51:56","date_gmt":"2015-05-21T17:51:56","guid":{"rendered":"http:\/\/depts.washington.edu\/cfrtc\/?p=548"},"modified":"2025-04-16T17:00:03","modified_gmt":"2025-04-17T00:00:03","slug":"pilot-2-hoffman","status":"publish","type":"post","link":"https:\/\/depts.washington.edu\/cfrtc\/pilot-2-hoffman\/","title":{"rendered":"Pilot 2 &#8211; Hoffman"},"content":{"rendered":"<p>[et_pb_section fb_built=&#8221;1&#8243; fullwidth=&#8221;on&#8221; _builder_version=&#8221;4.16&#8243; global_colors_info=&#8221;{}&#8221;][et_pb_fullwidth_slider admin_label=&#8221;Fullwidth Slider&#8221; module_id=&#8221;interior&#8221; _builder_version=&#8221;4.16&#8243; custom_padding=&#8221;|||&#8221; custom_padding_tablet=&#8221;|||&#8221; custom_padding_phone=&#8221;|||&#8221; box_shadow_style=&#8221;preset6&#8243; box_shadow_blur=&#8221;10px&#8221; box_shadow_color=&#8221;rgba(0,0,0,0.1)&#8221; show_inner_shadow=&#8221;on&#8221; global_colors_info=&#8221;{}&#8221; button_text_size__hover_enabled=&#8221;off&#8221; button_one_text_size__hover_enabled=&#8221;off&#8221; button_two_text_size__hover_enabled=&#8221;off&#8221; button_text_color__hover_enabled=&#8221;off&#8221; button_one_text_color__hover_enabled=&#8221;off&#8221; button_two_text_color__hover_enabled=&#8221;off&#8221; button_border_width__hover_enabled=&#8221;off&#8221; button_one_border_width__hover_enabled=&#8221;off&#8221; button_two_border_width__hover_enabled=&#8221;off&#8221; button_border_color__hover_enabled=&#8221;off&#8221; button_one_border_color__hover_enabled=&#8221;off&#8221; button_two_border_color__hover_enabled=&#8221;off&#8221; button_border_radius__hover_enabled=&#8221;off&#8221; button_one_border_radius__hover_enabled=&#8221;off&#8221; button_two_border_radius__hover_enabled=&#8221;off&#8221; button_letter_spacing__hover_enabled=&#8221;off&#8221; button_one_letter_spacing__hover_enabled=&#8221;off&#8221; button_two_letter_spacing__hover_enabled=&#8221;off&#8221; button_bg_color__hover_enabled=&#8221;off&#8221; button_one_bg_color__hover_enabled=&#8221;off&#8221; button_two_bg_color__hover_enabled=&#8221;off&#8221;][et_pb_slide _builder_version=&#8221;4.16&#8243; background_color=&#8221;#ffffff&#8221; background_image=&#8221;https:\/\/depts.washington.edu\/cfrtc\/wp-content\/uploads\/2014\/12\/microscope.jpg&#8221; global_colors_info=&#8221;{}&#8221; button_text_size__hover_enabled=&#8221;off&#8221; button_one_text_size__hover_enabled=&#8221;off&#8221; button_two_text_size__hover_enabled=&#8221;off&#8221; button_text_color__hover_enabled=&#8221;off&#8221; button_one_text_color__hover_enabled=&#8221;off&#8221; button_two_text_color__hover_enabled=&#8221;off&#8221; button_border_width__hover_enabled=&#8221;off&#8221; button_one_border_width__hover_enabled=&#8221;off&#8221; button_two_border_width__hover_enabled=&#8221;off&#8221; button_border_color__hover_enabled=&#8221;off&#8221; button_one_border_color__hover_enabled=&#8221;off&#8221; button_two_border_color__hover_enabled=&#8221;off&#8221; button_border_radius__hover_enabled=&#8221;off&#8221; button_one_border_radius__hover_enabled=&#8221;off&#8221; button_two_border_radius__hover_enabled=&#8221;off&#8221; button_letter_spacing__hover_enabled=&#8221;off&#8221; button_one_letter_spacing__hover_enabled=&#8221;off&#8221; button_two_letter_spacing__hover_enabled=&#8221;off&#8221; button_bg_color__hover_enabled=&#8221;off&#8221; button_one_bg_color__hover_enabled=&#8221;off&#8221; button_two_bg_color__hover_enabled=&#8221;off&#8221; sticky_transition=&#8221;on&#8221;][\/et_pb_slide][\/et_pb_fullwidth_slider][\/et_pb_section][et_pb_section fb_built=&#8221;1&#8243; _builder_version=&#8221;4.16&#8243; global_colors_info=&#8221;{}&#8221;][et_pb_row column_structure=&#8221;1_4,3_4&#8243; _builder_version=&#8221;4.16&#8243; background_size=&#8221;initial&#8221; background_position=&#8221;top_left&#8221; background_repeat=&#8221;repeat&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_column type=&#8221;1_4&#8243; _builder_version=&#8221;4.16&#8243; custom_padding=&#8221;|||&#8221; global_colors_info=&#8221;{}&#8221; custom_padding__hover=&#8221;|||&#8221;][et_pb_sidebar area=&#8221;et_pb_widget_area_10&#8243; admin_label=&#8221;Pilots Sidebar&#8221; _builder_version=&#8221;4.27.2&#8243; global_colors_info=&#8221;{}&#8221;][\/et_pb_sidebar][\/et_pb_column][et_pb_column type=&#8221;3_4&#8243; _builder_version=&#8221;4.16&#8243; custom_padding=&#8221;|||&#8221; global_colors_info=&#8221;{}&#8221; custom_padding__hover=&#8221;|||&#8221;][et_pb_text admin_label=&#8221;Text&#8221; _builder_version=&#8221;4.27.2&#8243; background_size=&#8221;initial&#8221; background_position=&#8221;top_left&#8221; background_repeat=&#8221;repeat&#8221; hover_enabled=&#8221;0&#8243; global_colors_info=&#8221;{}&#8221; sticky_enabled=&#8221;0&#8243;]<\/p>\n<h2 style=\"text-align: left;\">P30 CFRTC: Pilot 2<\/p>\n<p>Describing the CF gut microbiome in infancy and early childhood<\/p>\n<\/h2>\n<p>P.I.: <strong><a href=\"http:\/\/depts.washington.edu\/hofflab\/\" target=\"_blank\" rel=\"noopener\">Lucas Hoffman, MD, PhD<\/a><\/strong><br \/>\nAssociate Professor<br \/>\nDepartment of Pediatrics<br \/>\n<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=%28hoffman+l%5BAuthor%5D%29+AND+%28DK089507%5BGrants+and+Funding%5D%29&amp;sort=pubdate\">P30 CFRTC Publications<\/a><\/p>\n<p>Project Period: 2010 &#8211; 2013<\/p>\n<p>Abstract: Disease of the lungs and intestinal tract are responsible for the majority of the morbidity and mortality of cystic fibrosis (CF). The manifestations of CF intestinal disease during early life primarily involve pancreatic exocrine insufficiency that causes nutrient malabsorption and, bulky stools that can result in intestinal obstruction. In people without CF, a complex relationship between gut microbiota, nutritional intake, nutrient absorption, and other measures of health has been demonstrated. GI tract microbes are known to be an important contributor to human nutrient metabolism. In CF, GI tract microbes may represent an important determinant of CF nutritional outcomes, which in turn can significantly impact severity of lung disease and overall longevity. The microbial constituents of the CF intestine, nor their relationship with clinical outcomes, have been well studied. Furthermore, some work has suggested a correlation between colonization of the airway and intestine in individual CF patients with a single microbial species (<em>P. aeruginosa<\/em>). Therefore, the intestine may represent an important reservoir for airway infection.<\/p>\n<p>We hypothesize that the constituency of gut microbiota among children with CF (1) differs from that of children without CF, and (2) correlates with severity of malabsorption, vitamin deficiency, and nutritional state. To test these hypotheses, we propose a pilot study to establish methodology for studying gut microbiomes (as reflected by stool microbial content, defined with ultra high-throughput, culture independent molecular methods) among 10 infants and children with CF and age-matched non-CF controls. We will collect four stool samples per subject over a year to determine the within-subject variability of microbial characteristics and their relationship with the presence or absence of CF, with nutritional and clinical parameters (including weight, height, body mass index, growth rate of each of these parameters among both subject groups, and among CF subjects, serum vitamin levels, GI symptoms, and supplemental pancreatic enzyme dosage). Microbial species and gene content in stool samples will be defined using massively parallel next-generation DNA sequencing methods with which we have extensive experience. Estimates of the metabolic capability of the microbiome will be determined and correlated with these clinical parameters.<\/p>\n<p>Our goal in this pilot project is to apply these methods to collect sufficient preliminary data for a multicenter study of CF GI tract microbial species and gene content and their clinical relevance.[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section]<\/p>\n","protected":false},"excerpt":{"rendered":"<p>P.I.: Ian Sweet, PhD<br \/>\nResearch Associate Professor<br \/>\nMetabolism, Endocrinology and Nutrition<br \/>\nDirector, Islet Core, UW DERC<br \/>\nAffiliate Investigator, Benaroya Research Institute<\/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":"<p class=\"p6\"><span class=\"s2\"><b>P.I.: <\/b><a href=\"http:\/\/depts.washington.edu\/doce\/our-research\/facultyresearch-laboratories\/ian-sweet-phd\/\"><span class=\"s3\"><b>Ian Sweet, PhD<br \/> <\/b><\/span><\/a><\/span>Research Associate Professor<br \/> Metabolism, Endocrinology and Nutrition<br \/> Director, Islet Core, UW DERC<br \/> Affiliate Investigator, Benaroya Research Institute<\/p><p class=\"p6\">Cystic fibrosis (CF) is a congenital disease arising from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) and affects about 30,000 people nationwide. Mutations of the CFTR gene affect functioning of the chloride ion channels in epithelial cell membranes, leading to the many symptoms of CF. As CF patients age, there is an increased incidence of diabetes mellitus, occurring in almost half the patients with the disease. This form of diabetes has features of both type 1 and type 2 diabetes and is called Cystic Fibrosis Related Diabetes (CFRD). The most conceptually attractive factor responsible for the increased incidence of diabetes is diminished insulin secretion due to impaired beta cell function. We have obtained preliminary data showing that insulin secretion is significantly decreased in islets from CFTR knockout mice. Based on these data, we hypothesize that the loss of CFTR function is related to a loss in cAMP-stimulated insulin secretion. The PI of this application has been Director of the Islet Cell Functional Analysis Core, part of an NIDDK-funded Diabetes Research Center, for the last 10 years, and has established and validated a wide array of assays specifically to characterize biochemical mechanisms regulating islet secretory function involving metabolic, electrogenic and signaling factors. We propose to use these assays, as well as assays available through the Inflammation Core of the CF Research and Translation Center, to characterize and study the properties of islets from mouse models of CF that indicate the role of CFTR mutations in CFRD. To accomplish this, we will carry out 2 specific aims, one that will focus on in vitro experiments designed to determine the intracellular mechanisms mediating the impaired secretory function due to the CFTR mutation. The second aim will focus on in vivo conditions where it will be determined whether conditions resulting from the development of CF (as simulated by infecting mice with Pseudomonas aeruginosa) further decrease secretory function. The results of these studies will provide data that has both fundamental and clinical implications and will support a future R01 application to be submitted by the PI.<\/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\/548"}],"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=548"}],"version-history":[{"count":23,"href":"https:\/\/depts.washington.edu\/cfrtc\/wp-json\/wp\/v2\/posts\/548\/revisions"}],"predecessor-version":[{"id":3303,"href":"https:\/\/depts.washington.edu\/cfrtc\/wp-json\/wp\/v2\/posts\/548\/revisions\/3303"}],"wp:attachment":[{"href":"https:\/\/depts.washington.edu\/cfrtc\/wp-json\/wp\/v2\/media?parent=548"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/depts.washington.edu\/cfrtc\/wp-json\/wp\/v2\/categories?post=548"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/depts.washington.edu\/cfrtc\/wp-json\/wp\/v2\/tags?post=548"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}