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.
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.
|Donahue, Timothy R; Dawson, David W (2016) Leveraging Mechanisms Governing Pancreatic Tumorigenesis To Reduce Pancreatic Cancer Mortality. Trends Endocrinol Metab 27:770-781|
|Birtolo, Chiara; Pham, Hung; Morvaridi, Susan et al. (2016) 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 :|
|Yuan, Jingzhen; Pandol, Stephen J (2016) PKD signaling and pancreatitis. J Gastroenterol 51:651-9|
|Principe, Daniel R; DeCant, Brian; MascariÃ±as, Emman et al. (2016) TGFÎ² Signaling in the Pancreatic Tumor Microenvironment Promotes Fibrosis and Immune Evasion to Facilitate Tumorigenesis. Cancer Res 76:2525-39|
|Birtolo, Chiara; Go, Vay Liang W; Ptasznik, Andrzej et al. (2016) Phosphatidylinositol 3-Kinase: A Link Between Inflammation and Pancreatic Cancer. Pancreas 45:21-31|
|(2016) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 12:1-222|
|Moris, Maria; Dawson, David W; Jiang, Jennifer et al. (2016) Plectin-1 as a Biomarker of Malignant Progression in Intraductal Papillary Mucinous Neoplasms: A Multicenter Study. Pancreas 45:1353-8|
|Zhong, Zhenyu; Umemura, Atsushi; Sanchez-Lopez, Elsa et al. (2016) NF-ÎºB Restricts Inflammasome Activation via Elimination of Damaged Mitochondria. Cell 164:896-910|
|Toste, Paul A; Nguyen, Andrew H; Kadera, Brian E et al. (2016) Chemotherapy-Induced Inflammatory Gene Signature and Protumorigenic Phenotype in Pancreatic CAFs via Stress-Associated MAPK. Mol Cancer Res 14:437-47|
|Setiawan, Veronica Wendy; Pandol, Stephen J; Porcel, Jacqueline et al. (2016) Dietary Factors Reduce Risk of Acute Pancreatitis in a Large Multiethnic Cohort. Clin Gastroenterol Hepatol :|
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