The overall goal of Core C (Animal Use and Development Core) is to support the development and use of the animal models utilized within this Program Project Grant (PPG). The guiding principals for Core C are efficient planning and utilization of animals, standardization of processing and diagnoses, reliability of service and consistent evaluation of animal models and being a cost center for all animal costs. The fundamental expertise provided within the core is laboratory animal medicine and clinical and anatomic pathology. The Core is housed and coordinated in the Department of Veterinary Biosciences. Dr. Stefan Niewiesk, Core Director has been (Co-) Director of the Animal Core since 2004 and is an active collaborator with all Project Leaders for the PPG. He is certified in Veterinary Microbiology and as a Laboratory Animal Medicine Veterinarian (European). Dr. Thomas Rosol (Co-investigator), who is certified by the American College of Veterinary Pathology, will provide pathological evaluations for the Core. The overall theme of the PPG is to analyze how infection with HTLV-1 induces proliferation of CD4 T cells, how viral proteins and integration sites influence and maintain transformation and how the tumor cells interact with their microenvironment. After acute infection, HTLV-1 persists in the organism, eventually leading to oligoclonal and finally monoclonal proliferation and transformation of CD4+ T cells. After integration of the virus (Project 2; Kvaratskhelia), tumorigenesis is driven by the viral proteins Tax and Hbz (Projects 1 and 4; Green and Ratner), which includes altered patterns of expression of regulatory proteins. These leukemic cells spread throughout the organism and cause osteolysis and often hypercalcemia (Project 3; Weilbaecher and Rosol). All projects will use mice with a human immune system (HIS mice) as a model for adult T cell leukemia which has been established by Core C using a molecular clone of HTLV-1.

Public Health Relevance

The overall theme of the PPG is to analyze how infection with HTLV-1 induces proliferation of CD4 T cells, what cellular events occur during transformation and how the tumor cells interact with their microenvironment. After acute infection, HTLV-1 persists in the organism, eventually leading to oligoclonal and finally monoclonal proliferation and transformation of CD4 T cells. After integration of the virus (Project 2; Kvaratskhelia), tumorigenesis is driven by the viral proteins Tax and Hbz (Projects 1 and 4; Green and Ratner). These leukemic cells spread throughout the organism and cause osteolysis and often hypercalcemia (Project 3; Weilbaecher and Rosol). Core C supports the projects in the use and development of animal models.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA100730-15
Application #
9539608
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2018-09-01
Budget End
2019-08-31
Support Year
15
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Ohio State University
Department
Type
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Murali, Bhavna; Ren, Qihao; Luo, Xianmin et al. (2018) Inhibition of the Stromal p38MAPK/MK2 Pathway Limits Breast Cancer Metastases and Chemotherapy-Induced Bone Loss. Cancer Res 78:5618-5630
Huey, Devra D; Niewiesk, Stefan (2018) Production of Humanized Mice through Stem Cell Transfer. Curr Protoc Mouse Biol 8:17-27
Romeo, Megan; Hutchison, Tetiana; Malu, Aditi et al. (2018) The human T-cell leukemia virus type-1 p30II protein activates p53 and induces the TIGAR and suppresses oncogene-induced oxidative stress during viral carcinogenesis. Virology 518:103-115
Cherian, Mathew A; Olson, Sydney; Sundaramoorthi, Hemalatha et al. (2018) An activating mutation of interferon regulatory factor 4 (IRF4) in adult T-cell leukemia. J Biol Chem 293:6844-6858
Huey, Devra D; Bolon, Brad; La Perle, Krista M D et al. (2018) Role of Wild-type and Recombinant Human T-cell Leukemia Viruses in Lymphoproliferative Disease in Humanized NSG Mice. Comp Med 68:4-14
Pérès, Eléonore; Blin, Juliana; Ricci, Emiliano P et al. (2018) PDZ domain-binding motif of Tax sustains T-cell proliferation in HTLV-1-infected humanized mice. PLoS Pathog 14:e1006933
Panfil, Amanda R; Al-Saleem, Jacob; Howard, Cory M et al. (2018) Stability of the HTLV-1 Antisense-Derived Protein, HBZ, Is Regulated by the E3 Ubiquitin-Protein Ligase, UBR5. Front Microbiol 9:80
Kenney, Adam D; Dowdle, James A; Bozzacco, Leonia et al. (2017) Human Genetic Determinants of Viral Diseases. Annu Rev Genet 51:241-263
Webb, Lindsay M; Amici, Stephanie A; Jablonski, Kyle A et al. (2017) PRMT5-Selective Inhibitors Suppress Inflammatory T Cell Responses and Experimental Autoimmune Encephalomyelitis. J Immunol 198:1439-1451
Singh, Gatikrushna; Fritz, Sarah M; Ranji, Arnaz et al. (2017) Isolation of Cognate RNA-protein Complexes from Cells Using Oligonucleotide-directed Elution. J Vis Exp :

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