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 #
2P01CA100730-11A1
Application #
8742038
Study Section
Special Emphasis Panel (ZCA1-RPRB-J (M1))
Project Start
2014-09-23
Project End
2019-08-31
Budget Start
2014-09-23
Budget End
2015-08-31
Support Year
11
Fiscal Year
2014
Total Cost
$291,352
Indirect Cost
$76,720
Name
Ohio State University
Department
Type
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Panfil, Amanda R; Dissinger, Nathan J; Howard, Cory M et al. (2016) Functional Comparison of HBZ and the Related APH-2 Protein Provides Insight into Human T-Cell Leukemia Virus Type 1 Pathogenesis. J Virol 90:3760-72
Esser, Alison K; Schmieder, Anne H; Ross, Michael H et al. (2016) Dual-therapy with αvβ3-targeted Sn2 lipase-labile fumagillin-prodrug nanoparticles and zoledronic acid in the Vx2 rabbit tumor model. Nanomedicine 12:201-11
Su, Xinming; Esser, Alison K; Amend, Sarah R et al. (2016) Antagonizing Integrin β3 Increases Immunosuppression in Cancer. Cancer Res 76:3484-95
Kawatsuki, A; Yasunaga, J-I; Mitobe, Y et al. (2016) HTLV-1 bZIP factor protein targets the Rb/E2F-1 pathway to promote proliferation and apoptosis of primary CD4(+) T cells. Oncogene 35:4509-17
Murphy, Jane; Hall, William W; Ratner, Lee et al. (2016) Novel interactions between the HTLV antisense proteins HBZ and APH-2 and the NFAR protein family: Implications for the HTLV lifecycles. Virology 494:129-42
Niewiesk, Stefan (2016) Animals Models of Human T Cell Leukemia Virus Type I Leukemogenesis. ILAR J 57:3-11
Panfil, Amanda R; Martinez, Michael P; Ratner, Lee et al. (2016) Human T-cell leukemia virus-associated malignancy. Curr Opin Virol 20:40-46
Kroep, J R; Charehbili, A; Coleman, R E et al. (2016) Effects of neoadjuvant chemotherapy with or without zoledronic acid on pathological response: A meta-analysis of randomised trials. Eur J Cancer 54:57-63
Haines, Robyn A; Urbiztondo, Rebeccah A; Haynes 2nd, Rashade A H et al. (2016) Characterization of New Zealand White Rabbit Gut-Associated Lymphoid Tissues and Use as Viral Oncology Animal Model. ILAR J 57:34-43
Ratner, L; Rauch, D; Abel, H et al. (2016) Dose-adjusted EPOCH chemotherapy with bortezomib and raltegravir for human T-cell leukemia virus-associated adult T-cell leukemia lymphoma. Blood Cancer J 6:e408

Showing the most recent 10 out of 146 publications