The study of regulatory and accessory proteins and virus encoded enzymes of complex retroviruses such as human T-lymphotropic virus type 1 (HTLV-1) and human immunodeficiency virus (HIV) and have provided fundamental knowledge to define mechanisms of viral-induced transformation and basic paradigms of cell biology. This Program Project Grant (PPG) application is focused on using retrovirus models to elucidate basic cellular mechanisms governing transcriptional regulation of lymphocytes. This understanding will lead to new insights into the interface between pathogenic mechanisms of the virus during its replication and therapeutic modalities against retroviral-induced cancer. Each project will significantly expand ongoing collaborative efforts between the PPG laboratories. Project #1 is seeking to understand the essential role of p12I and p30II in transcriptional regulation in T-lymphocytes and in the establishment of HTLV-1 infection in vivo. Project #2 will extend the fundamental knowledge that defines the role of phosphorylation in HTLV Rex and thereby learn how this viral protein can be used to study mRNA transport in T-lymphocytes. Project #3 will test post-transcriptional control of retrovirus cell interaction through the use of novel control elements and retroviral vectors. Project #4 defines the role and regulation of parathyroid hormone related protein in ATL and its associated paraneoplastic syndrome, humoral hypercalcemia of malignancy in human and animal models. Project #5 continues the productive collaboration between The Ohio State University and Washington University, St. Louis to determine the role of the regulatory protein Tax in lymphocyte proliferation and virus-associated disease. Three interactive cores support the PPG: Administration/Biostatistics, Imaging, and Animal Models. The overall goal of the PPG is to use retrovirus models to define important mechanisms that determine lymphocyte proliferation and associated disease, as well as to test innovative modalities to ablate the effects of retroviral carcinogenesis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
3P01CA100730-04S1
Application #
7218445
Study Section
Subcommittee G - Education (NCI)
Program Officer
Ogunbiyi, Peter
Project Start
2003-04-21
Project End
2008-03-31
Budget Start
2006-05-05
Budget End
2007-03-31
Support Year
4
Fiscal Year
2006
Total Cost
$50,857
Indirect Cost
Name
Ohio State University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
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 :

Showing the most recent 10 out of 162 publications