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DartCF: The Dartmouth Cystic Fibrosis Research Center

DartCF：达特茅斯囊性纤维化研究中心

基本信息

批准号：
10686303
负责人：
DEAN R MADDEN
金额：
$ 120.82万
依托单位：
DARTMOUTH COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10686303
关键词：
Acceleration Address Affect Antibiotics Archives Area Award Basic Science Bioinformatics Biology Biostatistics Core Cessation of life Chronic Clinical Clinical Research Coculture Techniques Collaborations Communities Complex Coupled Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator Data Data Science Data Set Databases Development Diabetes Mellitus Disease Ecology Educational workshop Endowment Epithelium Evaluation Extramural Activities Faculty Fostering Foundations Functional disorder Funding Genetic Diseases Goals Immune Immune response Immunity Inflammatory Response Institution Intervention Investigation Liver diseases Longevity Lung Malnutrition Mediating Metabolic Microbe Mining Mission Modeling Monitor Mutation National Institute of Diabetes and Digestive and Kidney Diseases Organ Outcome Pancreatitis Pathogenesis Patients Pharmaceutical Preparations Pilot Projects Preclinical Drug Development Quality of life Research Research Personnel Resources Respiratory Tract Infections Services Signal Transduction Structure Symptoms System Therapeutic Tissues Training Translational Research Virulence Work antimicrobial base body system career development cohort commensal microbes community center complex data cystic fibrosis patients cystic fibrosis related diabetes data submission dysbiosis forging gastrointestinal gut dysbiosis gut microbes host-microbe interactions improved improved outcome innovation insight interest interoperability member microbial microbial community microbiome novel novel strategies novel therapeutic intervention novel therapeutics open data pathogenic microbe pre-clinical premature programs recruit synergism systemic inflammatory response tool translational study

项目摘要

In cystic fibrosis (CF), mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) unleash a cascade of clinical disorders, including chronic airway infections, systemic inflammation, microbial virulence, diabetes, malnutrition and liver disease. Great progress has been made in some areas of disease, and CFTR modulators provide dramatic benefits to some patients. Still, there is growing evidence of the interconnections among lung and gut dysbiosis and CF pathogenesis. As patients live longer, formerly rare symptoms are becoming more common. Thus, there is a pressing need to both understand and systematically treat the functional relationships between CFTR function, commensal and pathogenic microbes, metabolic states, and innate and acquired immune responses. Dartmouth has an interactive CF research team of 49 faculty members with extramural funding of $11.1M/year, studying epithelial biology, CFTR correction, host-microbe interactions, gut dysbiosis and immunity, as well as airway infections and antimicrobial strategies. The Dartmouth CF Research Center (DartCF) will build on progress made in the past year. We will deploy P30 and institutional funds to recruit new CF faculty, strengthen our research base, and foster interdisciplinary discovery. Our aims are: 1) to catalyze new research in CF basic and translational research in areas of interest to NIDDK; 2) to develop integrative strategies to understand and address CF pathobiology; 3) to create new research tools and support CF research through outstanding shared services; and 4) to build research capacity in CF locally, regionally, and nationally. We will focus P30 resources on 1) pioneering transparency and interoperability for CF datasets, 2) forging collaborations between CF and data-science researchers to mine these datasets for systems-level perspectives and 3) building on unique Dartmouth longitudinal patient cohorts to explore microbial community structure in the gut, host-microbe signaling, the effects of existing therapies, and implications for whole-body disease. A key theme is that dysbioses are interconnected, and that parallel investigations, coupled by powerful new data-science strategies can understand this complex underlying biology and reveal new therapeutic approaches. In parallel, we will leverage our research base to support early-stage preclinical target development. DartCF supports a variety of mechanisms. First, we fund a Pilot Project Project (P3) to develop new scientific opportunities in NIDDK-revelant areas and to recruit new faculty members to the Center. Second, we fund three scientific cores to support studies in CF: a Gastrointestinal Biology Core (GIBC), a Clinical and Translational Research Core (CTRC), and a CF Bioinformatics & Biostatistics Core (CF-BBC). Finally, we support an Enrichment and Research Administration Core (ERAC) to foster an interactive scientific community, sponsor retreats and courses, and track program progress. These efforts will identify new CF therapeutic opportunities, develop novel interventions, monitor the resulting changes body-wide, and track outcomes. DartCF will intensify the translation of research into improved CF outcomes at Dartmouth.

在囊性纤维化（CF）中，囊性纤维化跨膜传导调节因子（CFTR）的突变释放a