The Animal and Pathology Core is comprised of 2 sub-Cores. The Animal sub-Core will generate two severe experimental pancreatitis models: i) induced by choline deficient, ethionine-supplemented diet (CDE), and ii) bile-acid (taurolithocholate) pancreatic duct infusion on both wild type and Project-relevant genetically modified mice. Another critical task of this sub-Core is to generate and maintain colonies of knockout and transgenic mice used to address the shared studies as well as topics specific to individual Projects. The Pathology sub-Core will provide each Project with human tissue specimens to validate the relevance of the results obtained in animal and cell models of pancreatitis. The Pathology sub-Core will be also responsible for evaluation of all human tissue histologic sections. Due to potential variability in the quality of human tissues caused by necrosis and fibrosis, a standardized system of human tissue evaluation and quality control will be central to the Program's success. The Pathology sub-Core will also oversee the review and scoring of histopathological changes in experimental mouse models of pancreatitis as well as genetic models. The goals of the Core will be achieved by carrying out the following Specific Aims:
Aim 1 : To provide standardized animal models of pancreatitis, to maintain and generate colonies of genetically modified mice. 1a. Animal models of pancreatitis 1b. Maintenance of genetically modified mouse colonies 1c. Generation of new genetically modified mouse strains Aim 2: To provide human pancreatic tissues and pathohistologic evaluation of human and mouse pancreas tissues. The cost-reduction will be achieved by sharing among the Projects tissue samples from wild-type and genetically modified mice (both with and without pancreatitis) as well as human tissue specimens.

Public Health Relevance

Animal and Pathology Core: Narrative For all projects of the Program, the Animal and Pathology Core will (i) perform standardized mouse models of pancreatitis, which require significant expertise to ensure consistency of the results and appropriate management of animal welfare;(ii) maintain and generate colonies of genetically modified mice;(iii) provide human pancreatic tissues specimens;and (iv) provide expert histopathological evaluation of tissue sections from human and mouse pancreas. This will ensure high methodological quality, consistency and reproducibility of pancreatitis models, provide unique genetic mouse strains, and make available for Program investigators high-quality human pancreatitis tissue specimens. A significant cost-reduction will be achieved by sharing among the Projects tissue samples from wild-type and genetically modified mice (both with and without pancreatitis) as well as human tissue specimens.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
1P01DK098108-01A1
Application #
8743014
Study Section
Special Emphasis Panel (ZDK1)
Project Start
Project End
Budget Start
2014-09-01
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
DUNS #
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Yang, Zemin; Liu, Yu; Qin, Lan et al. (2017) Cathepsin H-Mediated Degradation of HDAC4 for Matrix Metalloproteinase Expression in Hepatic Stellate Cells: Implications of Epigenetic Suppression of Matrix Metalloproteinases in Fibrosis through Stabilization of Class IIa Histone Deacetylases. Am J Pathol 187:781-797
Setiawan, Veronica Wendy; Monroe, Kristine R; Pandol, Stephen J (2017) Reply. Clin Gastroenterol Hepatol 15:1139
Messenger, Scott W; Jones, Elaina K; Holthaus, Conner L et al. (2017) Acute acinar pancreatitis blocks vesicle-associated membrane protein 8 (VAMP8)-dependent secretion, resulting in intracellular trypsin accumulation. J Biol Chem 292:7828-7839
Bustos, Victor; Pulina, Maria V; Kelahmetoglu, Yildiz et al. (2017) Bidirectional regulation of A? levels by Presenilin 1. Proc Natl Acad Sci U S A 114:7142-7147
Bustos, Victor; Pulina, Maria V; Bispo, Ashley et al. (2017) Phosphorylated Presenilin 1 decreases ?-amyloid by facilitating autophagosome-lysosome fusion. Proc Natl Acad Sci U S A 114:7148-7153
Eibl, Guido; Cruz-Monserrate, Zobeida; Korc, Murray et al. (2017) Diabetes Mellitus and Obesity as Risk Factors for Pancreatic Cancer. J Acad Nutr Diet :
Birtolo, Chiara; Pham, Hung; Morvaridi, Susan et al. (2017) Cadherin-11 Is a Cell Surface Marker Up-Regulated in Activated Pancreatic Stellate Cells and Is Involved in Pancreatic Cancer Cell Migration. Am J Pathol 187:146-155
Gorelick, Fred S; Lerch, Markus M (2017) Do Animal Models of Acute Pancreatitis Reproduce Human Disease? Cell Mol Gastroenterol Hepatol 4:251-262
Lew, Daniel; Afghani, Elham; Pandol, Stephen (2017) Chronic Pancreatitis: Current Status and Challenges for Prevention and Treatment. Dig Dis Sci 62:1702-1712
Lugea, Aurelia; Gerloff, Andreas; Su, Hsin-Yuan et al. (2017) The Combination of Alcohol and Cigarette Smoke Induces Endoplasmic Reticulum Stress and Cell Death in Pancreatic Acinar Cells. Gastroenterology 153:1674-1686

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