Host-environment interactions in the pathophysiology of digestive disease

总体项目总结 本申请寻求对华盛顿大学DDRCC(WU-DDRCC)的持续支持。整体而言 WU-DDRCC的目标是创建一个支持协作、多学科的基础设施 消化系统疾病中宿主-环境相互作用的研究。WU-DDRCC提供支持 促进其50+22个正式成员的基础和翻译研究兴趣的技术， 并培养初级侦查员的职业发展。我们的研究基地效率很高，这是有目共睹的 引用DDRCC的248份原创同行评审出版物(60%反映涉及两个或两个以上的合作 成员)，包括58个发表在有影响因子的期刊上，并增加了资金支持(2380万美元$3090万； 自2013年以来增长了30%)。我们的成员在华盛顿的13个不同部门有预约 大学。研究基地的兴趣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、掌上皮病和癌症；(3) 代谢动态平衡、营养物质转运和肠肝信号传导。该研究基地由三个部门支持 利用机构资源的生物医学核心，并根据成员的需求进行了演变 以提供具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)一种新的精密动物模型和器官 核心(PAMOC)，提供老鼠遗传服务和有机类技术；和(3)生物库核心， 它提供了从正常和疾病状态访问临床生物菌种的途径。这些核心由 响应行政核心(ARAC)，由内部和外部咨询委员会指导，以促进 协作和协同互动，并支持反映当前和 研究基地未来的需求，具有最先进的服务和专业知识，提供成本- 有效和高效地。WU-DDRCC还支持一个科学浓缩项目，资助访问 研究人员和研讨会，以扩大科学环境，促进合作和刺激发展 消化系统疾病方面的新举措。充实计划也促进了学术事业的发展 通过培养博士后实习生、研究员和初级教员的兴趣，包括促进 通过有针对性的代表不足的少数族裔演讲者计划，为劳动力提供支持。WU-DDRCC已投资 在支持消化疾病研究领域建立未来领导者渠道方面的重大资源和努力 以及通过年度试点和可行性计划培养新的调查人员，该计划的 39：1该奖项过去15年(3个周期)的投资回报。此外，WU-DDRCC是 致力于促进和分享NIDDK资助的当地中心以及 通过中西部联盟和NIDDK中心方案，在区域范围内建立其他区域合作伙伴关系。总而言之，这些 取得的成就有助于推进对影响患者护理的消化系统疾病的发现。

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.