Retrovirus Models of Cancer

癌症逆转录病毒模型

基本信息

批准号：
9480887
负责人：
Patrick Lee Green
金额：
$ 10.91万
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/9480887
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

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（通过应用程序证明）：该计划项目的最终目标授予申请的最终目的是将trovirus介导的控制事件的Elucidate机制调节淋巴细胞增殖。 1型（HTLV-1）和HTLV-2，在我们的裂缝中开发或表征，并与已建立的动物模型（他的小鼠，转基因小鼠，兔子）联系起来，以测试疾病的分子决定因素。借助项目4（Ratner），将识别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与项目1（绿色）合作的解释，促进或维护。项目4（Ratner）将研究HTLV-1整合的分子机制和对病毒表达的选择性，Ultima tely发病机理（Weilbaecher和Rosol）将其专业知识与项目1、2 RAL表达相结合。表达肿瘤的HBZ将对骨化的骨骼减轻骨骼的骨骼减轻骨骼的形成，与项目1合作，项目4（Ratner）将识别和特征来确定替代NFκB激活的机制。介导的转换式项目由三个独特的共享核心支持：核心A（给药和生物统计学），核心B（蛋白质组学）和蛋白质分析）和核心C（动物模型的使用和开发）。 PPG中的研究人员实现了77位同行评审的手稿，PPG调查人员之间的合作是43％。定义转化机制和治疗性内部INTRV-1相关性白血病/淋巴瘤的研究并与Dcancers相关。