Retrovirus Models of Lymphocyte Transformation and Disease

淋巴细胞转化和疾病的逆转录病毒模型

• 批准号: 7937326
• 负责人: MICHAEL D. LAIRMORE
• 金额: $ 16.51万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7937326
• 关键词: Retrovirus; Models; Lymphocyte; Transformation; Disease

DESCRIPTION (provided by applicant): This competitive renewal application of P01 CA100730 seeks funds to continue the study of highly integrated retrovirus models to elucidate essential cellular mechanisms that define lymphocyte transformation and disease. The study of retroviruses has provided fundamental and critical knowledge for defining the mechanisms of cell transformation as well as fundamental paradigms of cell biology. The interactive nature, established record of collaborations, and focus of the individual projects and cores that constitute the proposed PPG continuation are directly supportive of NCI's strategic plans and goals. Our goals were realized with robust productivity over the last four years demonstrated by 64 peer-reviewed manuscripts 70% interactive between PPG investigators. The continuation of the Program will extend upon the established interactions through inter-related goals to define critical events that control the transition of lymphocytes from activation through immortalization and transformation. Project 1 uses retroviruses to provide novel insights into how they alter transcription and DNA damage/repair signaling to establish persistent infections and set the stage for cellular transformation. Project 2 (Dr. Green) will define novel post-transcriptional mechanisms of retroviruses and working together with Dr. Lairmore (Project 1), will comparatively test each protein in viral replication and lymphocyte transformation. Project 3 working collaboratively with multiple PPG investigators will examine the fundamental translational control mechanisms in both retroviruses and in crucial growth control genes. Project 4 (Drs. Weilbaecher, Washington University and Rosol, Ohio State University) combine their expertise with PPG investigators to study the role of bone microenvironment in osteolytic and osteoblastic tumor models. Project 5 (Dr. Ratner) continues the highly dynamic collaborations between each University to test the contribution of the inflammatory microenvironment in carcinogenesis using unique transgenic mouse models. The PPG consists of five interactive Projects and three highly supportive Cores. Each project is related to two central components involving the regulation of lymphocyte signaling and gene expression by retroviruses or alterations of the cellular microenvironment leading to transformation and paraneoplastic disease. The interactive nature of the PPG will provide rationale hypotheses to support translational studies to define therapeutic intervention against retrovirus-induced lymphoma and refine animal models to determine molecular determinants of retrovirus-induced cancer.

描述（由申请人提供）：P01 CA100730 的竞争性更新申请寻求资金继续研究高度集成的逆转录病毒模型，以阐明定义淋巴细胞转化和疾病的基本细胞机制。逆转录病毒的研究为定义细胞转化机制以及细胞生物学的基本范式提供了基础和关键知识。互动性质、既定的合作记录以及构成拟议 PPG 延续的各个项目和核心的重点都直接支持 NCI 的战略计划和目标。过去四年，我们的目标以强劲的生产力得以实现，64 份同行评审手稿（其中 70% 是 PPG 研究人员之间互动的）证明了这一点。该计划的延续将通过相互关联的目标来扩展已建立的相互作用，以定义控制淋巴细胞从激活到永生化和转化的转变的关键事件。项目 1 使用逆转录病毒提供新的见解，了解它们如何改变转录和 DNA 损伤/修复信号以建立持续感染并为细胞转化奠定基础。项目2（Green博士）将定义逆转录病毒的新型转录后机制，并与Lairmore博士（项目1）合作，比较测试病毒复制和淋巴细胞转化中的每种蛋白质。项目 3 与多个 PPG 研究人员合作，将研究逆转录病毒和关键生长控制基因的基本翻译控制机制。项目 4（华盛顿大学的 Weilbaecher 博士和俄亥俄州立大学的 Rosol 博士）将他们的专业知识与 PPG 研究人员结合起来，研究骨微环境在溶骨性和成骨细胞肿瘤模型中的作用。项目 5（拉特纳博士）继续各大学之间高度动态的合作，使用独特的转基因小鼠模型来测试炎症微环境在致癌作用中的作用。 PPG 由五个互动项目和三个高度支持的核心组成。每个项目都涉及两个核心组成部分，涉及逆转录病毒对淋巴细胞信号传导和基因表达的调节或导致转化和副肿瘤疾病的细胞微环境的改变。 PPG 的交互性质将为支持转化研究提供基本原理假设，以定义针对逆转录病毒诱导的淋巴瘤的治疗干预，并完善动物模型以确定逆转录病毒诱导的癌症的分子决定因素。