The overall objective of the Animal Core is to provide the Project Leaders with the ability to utilize animal carcinogenesis models in the execution of their research projects and to maintain genetically engineered animals for the investigation of the mechanisms involved in the pathogenesis of cancer. The Animal Core will serve as a resource for conducting the use of all animal manipulations needed in the program. The Animal Core will minimize the cost of utilizing animal models in the Program research projects by consolidating the equipment, expertise, and animal resources. This will ensure an efficient use of animal research at minimal cost and will reduce variables that could compromise data analysis among projects. The overall aims of the proposal are:
Specific Aim 1. Ensure the efficient planning, purchase, and utilization of experimental animals, including transgenic and genetically altered mice;maintain stocks of all animals;and breed animals for the individual Projects. We will maintain the animals needed for the Project's research and will work with the Project Leaders to identify and generate animals needed for the proposed studies.
Specific Aim 2. Provide the necessary facilities and expertise for carcinogenesis models to support the Research Projects. The Core will provide resources and expertise in animal models of cancer and inflammation. This will include colon, tongue (head &neck), breast, prostate, and lung carcinogenesis models using chemical carcinogens or genetically engineered mouse cancer models as well as inflammation models.
Specific Aim 3. Provide expertise in rodent pathology with up-to-date proficiency in cancer pathobiology. The Core director has extensive expertise in the area of pathology to provide the necessary infrastructure. The Core will organize the animal database including animal health and final pathological evaluations at necropsy. This database will be used to input all animal-specific results obtained by the Projects, to allow complex, cross-correlation-based data analysis. These efforts will facilitate the conduct of research in this proposal and will provide the expertise to support the Project Leaders. With the amalgamation of carcinogenesis models and genetically engineered mouse models in sphingolipids, this core is already evolving as a unique and enabling core that is critical for the success of the Program Project.
| Pulkoski-Gross, Michael J; Jenkins, Meredith L; Truman, Jean-Philip et al. (2018) An intrinsic lipid-binding interface controls sphingosine kinase 1 function. J Lipid Res 59:462-474 |
| Williams, Bianca; Correnti, Jason; Oranu, Amanke et al. (2018) A novel role for ceramide synthase 6 in mouse and human alcoholic steatosis. FASEB J 32:130-142 |
| Bai, Aiping; Bielawska, Alicja; Rahmaniyan, Mehrdad et al. (2018) Dose dependent actions of LCL521 on acid ceramidase and key sphingolipid metabolites. Bioorg Med Chem 26:6067-6075 |
| Newcomb, Benjamin; Rhein, Cosima; Mileva, Izolda et al. (2018) Identification of an acid sphingomyelinase ceramide kinase pathway in the regulation of the chemokine CCL5. J Lipid Res 59:1219-1229 |
| Espaillat, Mel Pilar; Snider, Ashley J; Qiu, Zhijuan et al. (2018) Loss of acid ceramidase in myeloid cells suppresses intestinal neutrophil recruitment. FASEB J 32:2339-2353 |
| Hannun, Yusuf A; Obeid, Lina M (2018) Sphingolipids and their metabolism in physiology and disease. Nat Rev Mol Cell Biol 19:175-191 |
| Schwartz, Nicholas U; Linzer, Ryan W; Truman, Jean-Philip et al. (2018) Decreased ceramide underlies mitochondrial dysfunction in Charcot-Marie-Tooth 2F. FASEB J 32:1716-1728 |
| Moorthi, Sitapriya; Burns, Tara Ann; Yu, Gui-Qin et al. (2018) Bcr-Abl regulation of sphingomyelin synthase 1 reveals a novel oncogenic-driven mechanism of protein up-regulation. FASEB J 32:4270-4283 |
| Morris, Thomas G; Borland, Samantha J; Clarke, Christopher J et al. (2018) Sphingosine 1-phosphate activation of ERM contributes to vascular calcification. J Lipid Res 59:69-78 |
| Coant, Nicolas; García-Barros, Mónica; Zhang, Qifeng et al. (2018) AKT as a key target for growth promoting functions of neutral ceramidase in colon cancer cells. Oncogene 37:3852-3863 |
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