Retrovirus Models of Cancer

癌症逆转录病毒模型

基本信息

批准号：
9391792
负责人：
Patrick Lee Green
金额：
$ 5.06万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-23 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9391792
关键词：
Adult T-Cell Leukemia/Lymphoma Affect Animal Model Animals Apoptotic Biostatistics Core CREB1 gene Cancer Model Cell Aging Cell Cycle Cell Death Cell physiology Cells Cellular biology Code Collaborations Complex Development Diagnosis Disease Enzymes Erinaceidae Etiology Event FOS gene FRAP1 gene Funding Gene Expression Genotype Goals Growth Homeostasis Human Human T-lymphotropic virus 1 Human T-lymphotropic virus 2 IL2RA gene Immune system In Vitro Infection JUN gene Knowledge Laboratories Link Lymphocyte Activation Lymphoma Lymphoproliferative Disorders MAP Kinase Gene Maintenance Malignant Neoplasms Manuscripts Mediating Messenger RNA Modeling Molecular Molecular Cloning Mouse Strains Mus Mutation NFKB Signaling Pathway Nature Neoplasms Oncogenes Oncogenic Viruses Oryctolagus cuniculus Osteoclasts Osteogenesis Pathogenesis Pathologist Pathway interactions Peer Review Phenotype Physicians Premalignant Cell Process Productivity Program Research Project Grants Protein Analysis Proteins Proteomics Provirus Integration RNA Research Research Personnel Resource Sharing Retroviridae Retroviridae Infections Role Scientist Signal Pathway Signal Transduction Signaling Protein Site Surface Syndrome T-Lymphocyte Taxes Testing Therapeutic Intervention Transforming Growth Factor beta Transgenic Mice Tumor Expansion Veterinarians Viral Virus Work activating transcription factor anticancer research bone bone turnover cancer type cell immortalization cell transformation effective therapy human tissue humanized mouse immortalized cell in vivo Model integration site leukemia/lymphoma leukemogenesis lymphocyte proliferation neoplastic new therapeutic target notch protein preneoplastic cell programs public health relevance receptor transcription factor translational study tumor tumor initiation

Adult T-Cell Leukemia/Lymphoma Affect Animal Model Animals Apoptotic Biostatistics Core CREB1 gene Cancer Model Cell Aging Cell Cycle Cell Death Cell physiology Cells Cellular biology Code Collaborations Complex Development Diagnosis Disease Enzymes Erinaceidae Etiology Event FOS gene FRAP1 gene Funding Gene Expression Genotype Goals Growth Homeostasis Human Human T-lymphotropic virus 1 Human T-lymphotropic virus 2 IL2RA gene Immune system In Vitro Infection JUN gene Knowledge Laboratories Link Lymphocyte Activation Lymphoma Lymphoproliferative Disorders MAP Kinase Gene Maintenance Malignant Neoplasms Manuscripts Mediating Messenger RNA Modeling Molecular Molecular Cloning Mouse Strains Mus Mutation NFKB Signaling Pathway Nature Neoplasms Oncogenes Oncogenic Viruses Oryctolagus cuniculus Osteoclasts Osteogenesis Pathogenesis Pathologist Pathway interactions Peer Review Phenotype Physicians Premalignant Cell Process Productivity Program Research Project Grants Protein Analysis Proteins Proteomics Provirus Integration RNA Research Research Personnel Resource Sharing Retroviridae Retroviridae Infections Role Scientist Signal Pathway Signal Transduction Signaling Protein Site Surface Syndrome T-Lymphocyte Taxes Testing Therapeutic Intervention Transforming Growth Factor beta Transgenic Mice Tumor Expansion Veterinarians Viral Virus Work activating transcription factor anticancer research bone bone turnover cancer type cell immortalization cell transformation effective therapy human tissue humanized mouse immortalized cell in vivo Model integration site leukemia/lymphoma leukemogenesis lymphocyte proliferation neoplastic new therapeutic target notch protein preneoplastic cell programs public health relevance receptor transcription factor translational study tumor tumor initiation

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项目摘要

DESCRIPTION (provided by applicant): The ultimate goal of this Program Project Grant competiting renewal application is to elucidate mechanisms of retrovirus-mediated disease or cellular control events that regulate lymphocyte proliferation/ transformation. A primary common thread among all research groups is the shared use of infectious molecular clones and derivatives of human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2, developed or characterized in our laboratories, and links to established animal models (HIS mice, transgenic mice, rabbits) to test molecular determinants of disease. Each Project Leader brings a unique Project that is interdependent on components of other Projects and Cores in the Program. Project 1 (Green) in collaboration with Project 4 (Ratner) will identify cellular interacting components of both Hbz RNA and protein and will use in vitro and in vivo models to determine the interplay between Hbz and Tax to uncover the mechanisms and pathways necessary for tumor initiation, promotion or maintenance. Project 2 (Kvaratskhelia) in collaboration with Project 1 (Green) and Project 4 (Ratner) will investigate the molecular mechanisms and roles of HTLV-1 integration site selectivity for proviral expression, cell transformation and ultimately pathogenesis. Project 3 (Weilbaecher and Rosol) combines their expertise with Projects 1, 2, and 4 to test the hypothesis that dysregulated tumoral expression of bone turnover factors in Tax and Hbz expressing tumors will reprogram the ATL bone microenvironment towards increased osteoclast resorption and decreased bone formation, which will favor tumor expansion in bone. Project 4 (Ratner) in collaboration with Project 1 will identify and characterize Tax-interactive proteins to determine the mechanism of action of alternative NFκB activation and determine the role of this pathway in Tax-mediated transformation. These four highly integrated Projects are supported by three unique shared resource cores: Core A (Administration and Biostatistics), Core B (Proteomics and Protein Analysis) and Core C (Animal Model Use and Development). For the past 5 years, investigators within this PPG realized robust productivity as demonstrated by 77 peer-reviewed manuscripts; 43% collaborative between PPG investigators. This competing renewal PPG assembles and integrates a unique team of physician scientists, basic scientists, lab animal veterinarians, and pathologists and will support interactive basic and translational studies to define transformation mechanisms and therapeutic intervention against HTLV-1 associated leukemia/lymphomas and other related cancers.

描述（应用程序提供）：该计划项目授予竞争竞争的最终目标是阐明逆转录病毒介导的疾病或细胞控制事件的机制，这些机制调节了调节淋巴细胞增殖/转化的细胞控制事件。所有研究小组中的主要共同线程是在我们的实验室中开发或表征的人类T细胞白血病病毒1型（HTLV-1）和HTLV-2的传染性分子克隆和衍生物的共同使用，以及与既定的动物模型（他的小鼠，转基因小鼠，Rabbits，Rabbits）的链接，以测试分子疾病的分子确定性。每个项目负责人都带来了一个独特的项目，该项目相互依赖于该计划中其他项目和核心的组件。项目1（绿色）与Project 4（Ratner）合作，将确定HBZ RNA和蛋白质的细胞相互作用组件，并将使用体外和体内模型来确定HBZ与税收之间的相互作用，以发现肿瘤倡议，促进或维持所需的机制和途径。项目2（Kvaratskhelia）与项目1（绿色）和项目4（Ratner）合作，将研究HTLV-1整合位点选择性的分子机制和作用，以促进表达，细胞转化和最终发病机理。项目3（Weilbaecher和Rosol）将其专业知识与项目1、2和4结合在一起，以检验以下假设：税收和HBZ表达肿瘤中骨转换因子的肿瘤表达失调，将重编程ATL骨微生物环境，朝着骨质分辨率分辨率和改善的骨骼形成，这将有利于肿瘤的肿瘤扩张。项目4（Ratner）与项目1合作将确定并表征税收相互作用的蛋白质，以确定替代NFκB激活的作用机理，并确定该途径在税收介导的转化中的作用。这四个高度集成的项目得到了三个独特的共享资源核心的支持：核心A（管理和生物统计学），核心B（蛋白质组学和蛋白质分析）和核心C（动物模型使用和开发）。在过去的5年中，该PPG中的调查人员实现了77个同行评审的手稿的强大生产力。 PPG调查人员之间的合作43％。这种竞争性的更新PPG组装，并整合了一个独特的物理科学家，基础科学家，实验室动物兽医和病理学家，并将支持互动性基础和翻译研究，以定义针对HTLV-1相关的白血病/淋巴瘤和其他相关癌症的转化机制和治疗干预。