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：
10240591
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/10240591
关键词：
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 Epithelial Evaluation Extramural Activities Faculty Fostering Foundations Functional disorder Funding Genetic Diseases Goals Immune Immune response Immunity Infection Inflammatory Response 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 Services Signal Transduction Structure Symptoms System Therapeutic Tissues Training Translational Research Virulence Work antimicrobial base body system career development cohort commensal microbes 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 ranpirnase recruit 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，囊性纤维化跨膜电导调节因子 (CFTR) 的突变会释放出一系列临床疾病，包括慢性气道感染、全身炎症、微生物毒力、糖尿病、营养不良和肝病。一些疾病领域取得了巨大进展，CFTR 调节剂给一些患者带来了巨大的好处。尽管如此，越来越多的证据表明它们之间存在相互联系肺和肠道菌群失调与 CF 发病机制之间的关系。随着患者寿命的延长，以前罕见的症状也变得更加常见。变得越来越普遍。因此，迫切需要了解并系统地治疗 CFTR 功能、共生微生物和病原微生物、代谢状态和先天性和获得性免疫反应。达特茅斯拥有一支由 49 名教职人员组成的互动 CF 研究团队每年拥有 1110 万美元的外部资金，研究上皮生物学、CFTR 校正、宿主-微生物相互作用、肠道菌群失调和免疫力，以及气道感染和抗菌策略。达特茅斯CF 研究中心（DartCF）将在过去一年取得的进展的基础上再接再厉。我们将部署P30和机构资金用于招募新的 CF 教师、加强我们的研究基础并促进跨学科发现。我们的目标是： 1) 促进 NIDDK 感兴趣领域的 CF 基础研究和转化研究的新研究； 2）到制定综合策略来理解和解决 CF 病理学问题； 3）创建新的研究工具通过出色的共享服务支持 CF 研究； 4) 建设本地 CF 研究能力，区域性和全国性。我们将把 P30 资源集中在 1) 开创 CF 的透明度和互操作性数据集，2）在 CF 和数据科学研究人员之间建立合作，挖掘这些数据集系统级视角和 3) 以独特的达特茅斯纵向患者队列为基础来探索微生物肠道中的群落结构、宿主微生物信号传导、现有疗法的效果以及对全身疾病。一个关键主题是生态失调是相互关联的，并且平行的研究，耦合通过强大的新数据科学策略可以理解这种复杂的基础生物学并揭示新的治疗方法。与此同时，我们将利用我们的研究基础来支持早期临床前目标发展。 DartCF 支持多种机制。首先，我们资助一个试点项目（P3）来开发 NIDDK 相关领域的新科学机会，并为该中心招募新的教职人员。第二，我们资助三个科学核心来支持 CF 研究：胃肠生物学核心 (GIBC)、临床和转化研究核心 (CTRC) 和 CF 生物信息学与生物统计学核心 (CF-BBC)。最后，我们支持浓缩和研究管理核心（ERAC）以培育互动的科学界，赞助静修会和课程，并跟踪计划进度。这些努力将确定新的 CF 治疗方法机会，制定新颖的干预措施，监测由此产生的全身变化，并跟踪结果。 DartCF 将加强研究成果的转化，以改善达特茅斯的 CF 结果。