The objective of the In Vivo Animal and Human Studies core is to provide a venue for focusing human resources, facilities, new technology and equipment necessary for the in vivo study of humans and animals. The core serves to fully integrate investigations at the molecular, cellular, and organ system levels that are currently being performed within other cores of the Center and enhance rapid translation of basic discoveries into clinical application. The major services provided by the In Vivo Animal and Human Studies core are as follows:1. To provide a variety of acute and chronic animal models as well as state-of-the-art in vivo technologies to enhance rapid translation of basic discoveries to physiological and clinical applications; 2. To develop an organoid and enteroid program in which these preparations grown from mucosa biopsies and induced pluripotent stem cells (iPSCs) may be used to study epithelial cell biology and provide therapeutic targets for clinical intervention; 3. To support a clinical study program which will provide consultation and technical support to Center investigators on design and statistical data analysis; and 4. To provide a user friendly, one-step service to access digestive disease-related biospecimens for Center members. Since its inception in 1984, the In Vivo Animal and Human Studies core has evolved to meet the needs of Center investigators. Over time, older techniques which are readily available in clinical facilities have been discontinued by the Center. We have streamlined our animal studies to include ones that are frequently utilized by Center investigators. These include mice endoscopy, in vivo cellular and molecular imaging studies in small animals, fluorescent-activated cell sorting (FACS) analysis, and electroporation for direct transfer of siRNA into targeted neuro-tissue or GI organs. The recent development of the Enteroid and Organoid core enables Center investigators to conduct research on in vitro models of human iPSCs, directed differentiation of human pluripotent stem cells (hPSCs), and 3-dimensional growth of primary human and mouse tissue delivered from the GI tract. These preparations may be used to study human GI development, homeostasis and disease in vitro. To enhance the rapid translation of basic science findings to clinical applications, the In Vivo Studies core has spent much of its efforts and resources to upgrade its infrastructure. The Clinical Design Program provides consultation regarding clinical study design, subject specification and sampling techniques, measurements and instruments, sample size estimation, power analysis, as well as data management and statistical analysis. The Biospecimen Banking service will provide support to enhance existing individual GI- related biobanks and develop future repositories. This service also centralizes, expedites, and facilitates access to GI-related biobanks and utilization of GI biospecimens to translate basic research within the paradigm of human specimens. During this funding period, the In Vivo Animal and Human Studies core has been used by 60% of its Center members, has supported 166 publications, with 55 being collaborative.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
5P30DK034933-32
Application #
9536011
Study Section
Special Emphasis Panel (ZDK1)
Project Start
Project End
Budget Start
2018-06-01
Budget End
2019-05-31
Support Year
32
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Dame, Michael K; Attili, Durga; McClintock, Shannon D et al. (2018) Identification, isolation and characterization of human LGR5-positive colon adenoma cells. Development 145:
Brady, Graham F; Kwan, Raymond; Ulintz, Peter J et al. (2018) Nuclear lamina genetic variants, including a truncated LAP2, in twins and siblings with nonalcoholic fatty liver disease. Hepatology 67:1710-1725
Wang, Zhen; Ocadiz-Ruiz, Ramon; Sundaresan, Sinju et al. (2018) Isolation of Enteric Glial Cells from the Submucosa and Lamina Propria of the Adult Mouse. J Vis Exp :
Kim, D-I; Liao, J; Emont, M P et al. (2018) An OLTAM system for analysis of brown/beige fat thermogenic activity. Int J Obes (Lond) 42:939-945
Park, Min-Jung; Iyer, Sapna; Xue, Xiang et al. (2018) HIF1-alpha Regulates Acinar Cell Function and Response to Injury in Mouse Pancreas. Gastroenterology 154:1630-1634.e3
Cho, Chun-Seok; Park, Hwan-Woo; Ho, Allison et al. (2018) Lipotoxicity induces hepatic protein inclusions through TANK binding kinase 1-mediated p62/sequestosome 1 phosphorylation. Hepatology 68:1331-1346
Tsai, Yu-Hwai; Czerwinski, Michael; Wu, Angeline et al. (2018) A Method for Cryogenic Preservation of Human Biopsy Specimens and Subsequent Organoid Culture. Cell Mol Gastroenterol Hepatol 6:218-222.e7
Morhardt, Tina L; Hayashi, Atsushi; Kao, John Y et al. (2018) Regional control of regulatory immune cells in the intestine. Curr Pathobiol Rep 6:29-34
Zhou, Shi-Yi; Gillilland 3rd, Merritt; Wu, Xiaoyin et al. (2018) FODMAP diet modulates visceral nociception by lipopolysaccharide-mediated intestinal inflammation and barrier dysfunction. J Clin Invest 128:267-280
Perry, Jeffrey W; Chen, Yanhua; Speliotes, Elizabeth et al. (2018) Functional Analysis of the Dengue Virus Genome Using an Insertional Mutagenesis Screen. J Virol 92:

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