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.

Public Health Relevance

OVERALL Research supported through the WU DDRCC has and will continue to have a profound impact on understanding the pathophysiology of digestive disease and the role of host-environment interactions. The WU DDRCC also promotes scientific collaboration and synergies that ultimately will identify new therapeutic opportunities with the potential for rapid translation into clinical trials for patients with digestive diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
2P30DK052574-21
Application #
9888917
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Perrin, Peter J
Project Start
2000-03-01
Project End
2024-11-30
Budget Start
2020-03-17
Budget End
2020-11-30
Support Year
21
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Song, Wilbur M; Joshita, Satoru; Zhou, Yingyue et al. (2018) Humanized TREM2 mice reveal microglia-intrinsic and -extrinsic effects of R47H polymorphism. J Exp Med 215:745-760
Bockerstett, Kevin A; Osaki, Luciana H; Petersen, Christine P et al. (2018) Interleukin-17A Promotes Parietal Cell Atrophy by Inducing Apoptosis. Cell Mol Gastroenterol Hepatol 5:678-690.e1
Willet, Spencer G; Lewis, Mark A; Miao, Zhi-Feng et al. (2018) Regenerative proliferation of differentiated cells by mTORC1-dependent paligenosis. EMBO J 37:
Bando, Jennifer K; Gilfillan, Susan; Song, Christina et al. (2018) The Tumor Necrosis Factor Superfamily Member RANKL Suppresses Effector Cytokine Production in Group 3 Innate Lymphoid Cells. Immunity 48:1208-1219.e4
Gathungu, Grace; Zhang, Yuanhao; Tian, Xinyu et al. (2018) Impaired granulocyte-macrophage colony-stimulating factor bioactivity accelerates surgical recurrence in ileal Crohn's disease. World J Gastroenterol 24:623-630
Feng, Jing; Luo, Jialie; Yang, Pu et al. (2018) Piezo2 channel-Merkel cell signaling modulates the conversion of touch to itch. Science 360:530-533
Zhang, Daoxiang; Li, Lin; Jiang, Hongmei et al. (2018) Tumor-Stroma IL1?-IRAK4 Feedforward Circuitry Drives Tumor Fibrosis, Chemoresistance, and Poor Prognosis in Pancreatic Cancer. Cancer Res 78:1700-1712
Sullender, Meagan E; Baldridge, Megan T (2018) Norovirus interactions with the commensal microbiota. PLoS Pathog 14:e1007183
Eberth, Jan M; Josey, Michele J; Mobley, Lee R et al. (2018) Who Performs Colonoscopy? Workforce Trends Over Space and Time. J Rural Health 34:138-147
Luo, Jialie; Feng, Jing; Yu, Guang et al. (2018) Transient receptor potential vanilloid 4-expressing macrophages and keratinocytes contribute differentially to allergic and nonallergic chronic itch. J Allergy Clin Immunol 141:608-619.e7

Showing the most recent 10 out of 899 publications