Host-environment interactions in the pathophysiology of digestive disease

项目概要 本申请寻求对华盛顿大学DDRCC（WU-DDRCC）的持续支持。整体 WU-DDRCC的目标是建立一个支持协作、多学科、 消化系统疾病中宿主-环境相互作用的研究。WU-DDRCC提供了 促进其50个正式成员和22个准成员的基础和转化研究兴趣的技术， 并培养初级调查员的职业发展。我们的研究基地是高产证明 248篇引用DDRCC的原始同行评审出版物（60%反映了涉及两个或两个以上的合作 成员），包括58个影响因子>10的期刊，并增加了资金支持（2380万美元至3090万美元; 自2013年以来增长30%）。我们的成员在华盛顿的13个不同部门都有任命 大学研究基地的利益是围绕三个机械主题组织：（1）宿主微生物 相互作用、炎症和粘膜免疫;（2）干细胞、上皮更新、发灰病和癌症;（3） 代谢稳态、营养转运和肝肠信号传导。研究基地由三个 生物医学核心利用机构资源，并根据成员的需求不断发展 提供具有成本效益的基础设施。这些核心包括（1）高级成像和组织分析核心 （2）新的精密动物模型和类器官 核心（PAMOC），提供小鼠遗传服务和类器官技术;以及（3）生物库核心， 其提供对来自正常和疾病状态的临床生物样本的访问。这些核心由 在内部和外部咨询委员会的指导下，建立一个反应迅速的行政核心， 协作和协同互动，并支持反映当前和 研究基地的未来需求与国家的最先进的服务和专业知识，交付成本- 有效和高效。WU-DDRCC还支持一项科学充实计划， 研究人员和讲习班，以扩大科学环境，促进合作和刺激发展 消化系统疾病的新举措。丰富计划还促进学术职业发展 通过培养博士后学员、研究员和初级教师的兴趣，包括促进 通过有针对性的代表性不足的少数民族发言人计划的劳动力。WU-DDRCC已投资 通过支持，投入大量资源和精力，建立消化系统疾病研究未来领导者的管道 通过年度试点和可行性计划培养新的调查人员， 在过去15年（3个周期）的投资回报率为39：1。此外，WU-DDRCC还 致力于促进和分享技术发展与NIDDK资助的中心在当地以及 通过中西部联盟和NIDDK中心计划，在区域范围内与其他DDRCC合作。总的来说，这些 这些成就有助于促进消化系统疾病的发现，这将影响病人的护理。

PROJECT SUMMARY OVERALL This application seeks continued support for the Washington University DDRCC (WU-DDRCC). The overall objective of the WU-DDRCC is to create an infrastructure that supports collaborative, multidisciplinary investigation into host-environment interactions in digestive disease. The WU-DDRCC provides enabling technology that promotes the basic and translational research interests of its 50 Full + 22 Associate members, and nurtures career development of junior investigators. Our Research Base is highly productive as evidenced by 248 original peer reviewed publications citing the DDRCC (60% reflecting collaborations involving two or more members), including 58 in journals with impact factors >10, and increased funding support ($23.8M$30.9M; 30% increase since 2013). Our members have appointments in 13 different Departments across Washington University. The Research Base interests are organized around three mechanistic themes: (1) Host-microbial interactions, inflammation and mucosal immunity; (2) Stem cells, epithelial renewal, paligenosis and cancer; (3) Metabolic homeostasis, nutrient transport and enterohepatic signaling. The Research Base is supported by three Biomedical Cores that leverage institutional resources, and which have evolved in response to members' needs to provide a cost-effective infrastructure. These Cores include (1) Advanced Imaging and Tissue Analysis Core (AITAC), which provides sophisticated imaging technologies; (2) A new Precision Animal Models and Organoids Core (PAMOC), which provides mouse genetic services and organoid technologies; and (3) a Biobank Core, which provides access to clinical biospecimens from normal and disease states. These Cores are overseen by a responsive Administrative Core (ARAC), guided by both Internal and External Advisory Boards to promote collaborative and synergistic interactions and support Biomedical Cores and services that reflect current and future needs of the Research Base with state-of-the-art services and specialized expertise, delivered cost- effectively and efficiently. The WU-DDRCC also supports a scientific Enrichment Program sponsoring visiting researchers and workshops to augment the scientific milieu, promote collaboration and stimulate development of new initiatives in digestive disease. The Enrichment Program also promotes academic career development by nurturing the interests of postdoctoral trainees, fellows and junior faculty, including promoting diversity in the workforce through a targeted Underrepresented Minority speaker program. The WU-DDRCC has invested significant resources and effort in building a pipeline of future leaders in digestive disease research by supporting and nurturing new investigators through an annual Pilot and Feasibility Program for which there is greater than 39:1 return on investment over the last 15 Years (3 cycles) of this award. In addition, the WU-DDRCC is committed to promoting and sharing technology development with NIDDK funded Centers locally as well as other DDRCCs regionally, through the Midwest Alliance and the NIDDK Center program. Collectively, these accomplishments serve to advance discovery in digestive disease that will impact patient care.