The Integrated Physiology Core is a multi-service resource that provides Center Investigators and their laboratories the tools and advice needed to establish and study mouse (including transgenic and knockout) and human (i.e. 3D organoid cultures) models of gastrointestinal disease. Since the inception of our Center, this Core has expanded its use by the Research Base and become a highly cost effective and efficient resource for histology, genotyping, and physiology services. This Core also provides the Research Base with the training and resources to utilize human intestinal stem cell technology for their studies. The use of human intestinal stem cell derived enteroids/colonoids has rapidly evolved and is becoming a premier model for the study of human GI physiology and pathophysiology. During the initial funding period, the Core was used by 46 Core Center investigators (>70% utilized multiple services), resulting in 65 published manuscripts, and has been used by 7 out of 11 funded P/F projects. The services offered include 1) Advice on establishing and maintaining mouse colonies, including how to breed onto uniform backgrounds; 2) Genotyping, which includes developing and optimizing primers; 3) Histological services, which include tissue fixation and processing, embedding, sectioning (including cryosectioning), histopathological staining (e.g. H&E, PAS, Sirius Red), and tissue archiving. A tissue bank of H&E slides of GI organs of the mouse models studied by our Research Base are made available for other Core members to use for preliminary studies; 4) Histopathology consultation by an expert pathologist for characterization of mouse GI disease models; 5) Metabolic cages are available for metabolic balance studies, including blood, urine, stool analysis; 6) Ussing chamber/voltage clamp technology for measuring active ion transport and tight junction permeability and permselectivity;7) Multiplex ELISA for simultaneous measurement of ~100 analytes (e.g. cytokines, chemokines, growth factors) from a small volume (<100?l) sample of serum, tissue, or culture media; as well as 8) Training in establishing, maintaining, and using mouse and human enteroids as well as provision of growth factor conditioned media necessary for long- term culture.

Public Health Relevance

Integrated Physiology Core C: Narrative The Hopkins Conte DDBTRCC Integrated Physiology Core is a multi-service Core that provides our Research Base the training, resources and equipment to study mouse and human models to increase understanding of the physiology and pathophysiology of gastrointestinal diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
2P30DK089502-06
Application #
8969782
Study Section
Special Emphasis Panel (ZDK1)
Project Start
2011-06-01
Project End
2021-05-31
Budget Start
2016-09-01
Budget End
2017-08-31
Support Year
6
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Avula, Leela Rani; Chen, Tiane; Kovbasnjuk, Olga et al. (2018) Both NHERF3 and NHERF2 are necessary for multiple aspects of acute regulation of NHE3 by elevated Ca2+, cGMP, and lysophosphatidic acid. Am J Physiol Gastrointest Liver Physiol 314:G81-G90
Moinova, Helen R; LaFramboise, Thomas; Lutterbaugh, James D et al. (2018) Identifying DNA methylation biomarkers for non-endoscopic detection of Barrett's esophagus. Sci Transl Med 10:
Liu, Xi; Abraham, John M; Cheng, Yulan et al. (2018) Synthetic Circular RNA Functions as a miR-21 Sponge to Suppress Gastric Carcinoma Cell Proliferation. Mol Ther Nucleic Acids 13:312-321
Liu, Xi; Cheng, Yulan; Abraham, John M et al. (2018) Modeling Wnt signaling by CRISPR-Cas9 genome editing recapitulates neoplasia in human Barrett epithelial organoids. Cancer Lett 436:109-118
Dejea, Christine M; Fathi, Payam; Craig, John M et al. (2018) Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria. Science 359:592-597
Aberle, M R; Burkhart, R A; Tiriac, H et al. (2018) Patient-derived organoid models help define personalized management of gastrointestinal cancer. Br J Surg 105:e48-e60
Singh, Varsha; Yang, Jianbo; Yin, Jianyi et al. (2018) Cholera toxin inhibits SNX27-retromer-mediated delivery of cargo proteins to the plasma membrane. J Cell Sci 131:
Chung, Liam; Thiele Orberg, Erik; Geis, Abby L et al. (2018) Bacteroides fragilis Toxin Coordinates a Pro-carcinogenic Inflammatory Cascade via Targeting of Colonic Epithelial Cells. Cell Host Microbe 23:203-214.e5
Liu, Liansheng; Zhu, Yaohui; Noë, Michaël et al. (2018) Neuronal Transforming Growth Factor beta Signaling via SMAD3 Contributes to Pain in Animal Models of Chronic Pancreatitis. Gastroenterology 154:2252-2265.e2
Nakamura, Hideki; Lee, Albert A; Afshar, Ali Sobhi et al. (2018) Intracellular production of hydrogels and synthetic RNA granules by multivalent molecular interactions. Nat Mater 17:79-89

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