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Retrovirus Models of Lymphocyte Transformation/Disease

淋巴细胞转化/疾病的逆转录病毒模型

基本信息

批准号：
7458547
负责人：
MICHAEL D. LAIRMORE
金额：
$ 5.43万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-04-21 至 2008-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7458547
关键词：
Address Adenovirus E1A Proteins Adult Affect Americas Amino Acids Animal Model Apoptosis Applications Grants Area Assimilations Atrophic Attention BHLH Protein Binding Biological Biological Models Biology Biometry Calcium Cancer Biology Cancer Center Cancer Etiology Cancer Research Project Cell Communication Cell Cycle Cell Line Cell Nucleus Cell model Cell physiology Cells Cellular biology Centers for Disease Control and Prevention (U.S.)Chalk Chromosomes Class Classification Clinical Collaborations Complex Comprehensive Cancer Center Cyclic AMP-Responsive DNA-Binding Protein Cytoplasm DNA DNA Viruses Data Defect Deoxyribonuclease I Deoxyribonucleases Development Disease Disease Outcome Disease Pathway Disease Progression Disruption Dissection EP300 gene Elements Elevation Environment Enzymes Event Exhibits Extramural Activities Faculty Family Felidae Fingers Fostering Foundations Funding Gagging Gene Expression Gene Expression Regulation Gene Transfer Genes Genetic Genetic Transcription Genome Glean Goals Growth HIV HIV-1 Hand Helper-Inducer T-Lymphocyte Heterogeneous Nuclear RNA Homeostasis Hormones Human Human Cloning Human T-lymphotropic virus 1 Human T-lymphotropic virus 2 Hypercalcemia Hypercalcemia of Malignancy I Kappa B-Alpha Image Immune Immunologic Deficiency Syndromes In Vitro Indium Individual Infection Infectious Agent Inflammatory Interdisciplinary Study Interleukin-2 Introns Joints Knowledge Laboratories Laboratory Research Large T Antigen Lead Learning Length Lentivirus Vector Lesion Licensing Life Cycle Stages Lighting Link Localized Lymphocyte Lymphocyte Activation Lymphoma Lymphoproliferative Disorders Lytic Mad1 protein Maintenance Malignant Neoplasms Manuscripts Mason-Pfizer monkey virus Mediating Membrane Membrane Potentials Mesenchymal Cell Neoplasm Messenger RNA Methodology Methods Mitochondria Mitotic Modality Modeling Molecular Molecular Cloning Molecular Profiling Mononuclear Morbidity - disease rate Morphology Mus NF-kappa B National Cancer Institute Nature Necrosis Neoplastic Cell Transformation Neurologic Nuclear Nuclear Export Ohio Oncogene Proteins Oncogenes Oncogenic Viruses Open Reading Frames Osteoclasts Outcome Paraneoplastic Syndromes Participant Pathogenesis Pathway interactions Patients Peripheral Personal Satisfaction Phase Phenotype Phosphoproteins Phosphorylation Polyomavirus Population Positioning Attribute Post-Transcriptional Regulation Postdoctoral Fellow Premature Mortality Prevention Principal Investigator Process Program Research Project Grants Property Protein Kinase Protein p53 Proteins Proviruses Publications Purpose Qualifying RNA RNA Splicing RNA Transport Reagent Receptor Activation Receptor Cell Recording of previous events Recruitment Activity Regulation Reporting Research Research Design Research Personnel Research Project Grants Retroviral Vector Retroviridae Retroviridae Infections Role SCID Beige Mouse SCID Mice Satellite Viruses Schedule Series Serine Serum Response Factor Signal Transduction Site Solutions Spleen Staging Stimulus Structure Students System T Cell Receptor Signaling Pathway T-Cell Development T-Cell Lymphoma T-Cell Receptor T-Lymphocyte Taxes Testing Therapeutic Therapeutic Intervention Threonine Time Transcription Coactivator Transcriptional Regulation Transgenic Mice Transgenic Model Transgenic Organisms Translation Initiation Translations Transplantation Tumor Suppressor Proteins Tumor-Derived Universities Untranslated Regions Vaccines Viral Viral Genome Viral Proteins Viral Reverse Transcription Virion Virus Virus Cancer Research Virus Diseases Virus Latency Virus Replication Visit War Washington Welts Work Zinc anticancer research apoptosis in lymphocytes base bone brachyury protein (T protein), human cancer imaging carcinogenesis cell transformation cellular targeting concept cyclin D3 design gene transfer vector genetic regulatory protein granzyme B in vivo in vivo Model inhibitor/antagonist innovation insight interdisciplinary approach interest leukemia lymphocyte proliferation mRNA Expression mRNA Precursor member metaplastic cell transformation mineralization mortality mouse model mutant neoplastic cell novel novel therapeutics p27 Cell Cycle Protein p27 Enzyme Inhibitor parathyroid hormone-related protein pol genes pre-clinical programs promoter protein expression ranpirnase receptor research study response tax Genes therapeutic gene therapeutic target tool transcription factor transcription factor USF transgene expression tumor vector vector control viral RNA virus host interaction

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：对人类 T 淋巴细胞病毒 1 型 (HTLV-1) 和人类免疫缺陷病毒 (HIV) 等复杂逆转录病毒的调节蛋白和辅助蛋白以及病毒编码酶的研究，为定义病毒诱导转化的机制和细胞生物学的基本范式提供了基础知识。该计划项目拨款 (PPG) 申请的重点是使用逆转录病毒模型来阐明控制淋巴细胞转录调节的基本细胞机制。这种理解将使人们对病毒复制过程中的致病机制与逆转录病毒诱导的癌症的治疗方式之间的相互作用产生新的见解。每个项目都将显着扩大 PPG 实验室之间正在进行的合作。项目 #1 旨在了解 p12I 和 p30II 在 T 淋巴细胞转录调节和体内 HTLV-1 感染建立中的重要作用。项目 #2 将扩展定义 HTLV Rex 中磷酸化作用的基础知识，从而了解如何使用这种病毒蛋白来研究 T 淋巴细胞中的 mRNA 转运。项目 #3 将通过使用新型控制元件和逆转录病毒载体来测试逆转录病毒细胞相互作用的转录后控制。项目 #4 定义了甲状旁腺激素相关蛋白在 ATL 及其相关副肿瘤综合征、人类和动物模型中恶性肿瘤的体液高钙血症中的作用和调节。项目 #5 继续俄亥俄州立大学和圣路易斯华盛顿大学之间的富有成效的合作，以确定调节蛋白 Tax 在淋巴细胞增殖和病毒相关疾病中的作用。三个交互式核心支持 PPG：管理/生物统计学、成像和动物模型。 PPG 的总体目标是利用逆转录病毒模型来定义决定淋巴细胞增殖和相关疾病的重要机制，并测试消除逆转录病毒致癌作用的创新模式。