DartCF: The Dartmouth Cystic Fibrosis Research Center

DartCF：达特茅斯囊性纤维化研究中心

• 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
• 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

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）的突变释放了一种新的信号通路。 临床疾病的级联，包括慢性气道感染，全身性炎症，微生物毒力， 糖尿病、营养不良和肝病。在某些疾病领域取得了很大进展， 调节剂为一些患者提供显著的益处。尽管如此，有越来越多的证据表明， 肺和肠道生态失调和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 变得越来越普遍。因此，迫切需要了解和系统地处理 CFTR功能、肠道和病原微生物、代谢状态和 先天性和获得性免疫反应。达特茅斯有一个由49名教员组成的交互式CF研究团队 每年有1110万美元的校外资金，研究上皮生物学，CFTR校正，宿主-微生物相互作用， 肠道生态失调和免疫力，以及气道感染和抗菌策略。达特茅斯足球俱乐部 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 基金招募新的CF教师，加强我们的研究基础，并促进跨学科的发现。我们的目标 是：1）在NIDDK感兴趣的领域促进CF基础和转化研究的新研究; 2） 制定综合战略，以了解和解决CF病理生物学; 3）创建新的研究工具， 通过优秀的共享服务支持CF研究; 4）在本地建立CF的研究能力， 区域和国家。我们将把P30资源集中在1）开创CF的透明度和互操作性上 数据集，2）在CF和数据科学研究人员之间建立合作，以挖掘这些数据集， 系统层面的观点和3）建立在独特的达特茅斯纵向患者队列，以探索微生物 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 全身疾病一个关键的主题是，生态失调是相互关联的，平行的调查， 通过强大的新数据科学策略，可以理解这种复杂的潜在生物学，并揭示新的 治疗方法。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）， 在NIDDK相关领域的新的科学机会，并招募新的教师到中心。第二、 我们资助了三个科学核心来支持CF的研究：胃肠道生物学核心（GIBC），临床和 转化研究核心（CTRC）和CF生物信息学和生物统计学核心（CF-BBC）。最后我们 支持一个丰富和研究管理核心（ERAC），以促进一个互动的科学界， 赞助务虚会和课程，并跟踪项目进展。这些努力将确定新的CF治疗 机会，开发新的干预措施，监测由此产生的变化全身，并跟踪结果。 DartCF将在达特茅斯加强研究转化为改善CF结果。