DartCF: The Dartmouth Cystic Fibrosis Research Center

在囊性纤维化(CF)中，囊性纤维化跨膜传导调节因子(CFTR)突变释放了一种 一连串的临床疾病，包括慢性呼吸道感染、全身炎症、微生物毒力、 糖尿病、营养不良和肝病。在疾病的一些领域取得了很大进展，CFTR 调节剂为一些患者提供了巨大的好处。尽管如此，越来越多的证据表明这种相互联系 肺肠失调与CF发病机制的关系。随着患者寿命的延长，以前罕见的症状是 变得越来越普遍。因此，迫切需要理解并系统地对待 CFTR功能、共生微生物和致病微生物、代谢状态和 先天和后天免疫反应。达特茅斯大学有一个由49名教职员工组成的互动式CF研究团队 每年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、 肠道生物失调和免疫，以及呼吸道感染和抗菌策略。达特茅斯的CF 研究中心(DartCF)将在过去一年取得进展的基础上再接再厉。我们将部署P30和机构 资金用于招聘新的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)在NIDDK感兴趣的领域催化新的CF基础研究和翻译研究；2) 制定综合战略，以了解和解决CF病理生物学问题；3)创建新的研究工具和 通过出色的共享服务支持林业研究；以及4)在当地建设林业研究能力， 在地区和全国范围内都是如此。我们将把P30资源集中于1)开创性的CF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，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上以探索微生物 肠道中的群落结构，宿主-微生物信号，现有治疗的效果，以及对 全身疾病。一个关键的主题是，生物失调是相互关联的，平行的研究，加上 通过强大的新数据科学战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)来开发 在NIDDK相关领域提供新的科学机会，并为中心招聘新的教职员工。第二, 我们资助了三个科学核心来支持CF的研究：一个胃肠道生物学核心(GIBC)，一个临床和 翻译研究核心(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治疗方法 机会，开发新的干预措施，在整个身体范围内监测由此产生的变化，并跟踪结果。 达特茅斯将加强将研究转化为改善达特茅斯会议成果的研究。

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.