Molecular Biology and Genetics of Human Tumor Viruses

人类肿瘤病毒的分子生物学和遗传学

• 批准号: 10898452
• 负责人: PAUL F. LAMBERT
• 金额: $ 50万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10898452
• 关键词: Administrative Supplement; Bioinformatics; Cancer Etiology; Disease; Engineering; Etiology; Family; Funding; Genes; Genome; Goals; Herpesviridae; Histology; Human; Human Biology; Human Genetics; Human Herpesvirus 4; Human Papilloma Virus-Related Malignant Neoplasm; Institution; Kaposi Sarcoma; Left; Letters; Life Cycle Stages; Lytic; Malignant Neoplasms; Microscopy; Molecular Biology; Molecular Genetics; Oncogenic Viruses; Papillomavirus; Pathway interactions; Prevention; Production; Program Research Project Grants; Translating; Viral; Virus; Virus Diseases; cancer therapy; carcinogenesis; cell type; cost; instrumentation; live cell imaging; novel strategies; prevent; statistics; tumor; virus related cancer

PROJECT SUMMARY/ABSTRACT Viruses cause approximately 15% of human cancers. A viral etiology to a human cancer can have substantive consequences on its treatment and prevention. For example, many virally-caused human cancers express virally encoded products, which are potential targets for anti-viral, tumor-specific therapies. In addition, unique sets of cellular genes and pathways contribute to virally-associated cancers, many of which are currently being pursued as targets for anti-cancer therapies. This program project grant (PPG) has two major objectives: to use molecular biology and genetics to elucidate the life cycles of and transformation by human tumor viruses and to translate this understanding into the identification of targets for specific anti-viral, anti-tumor therapies. We are focused on studying human tumor viruses in three different virus families: papillomaviruses, Epstein Barr Virus, and Kaposi Sarcoma Virus. Together, these three families of viruses cause many of the virally-associated human cancers. This request for an Administrative Supplement to provide 5 months of bridge funding, until the competitive renewal is funded in early 2024 is to support 4 of the 5 projects in the current PPG (the one project left out has been sunsetted because Dr. Dan Loeb, Project Leader for Project 2, has retired). The goals of the four projects are: Project 1) to identify and characterize cellular genes that drive human papillomavirus-associated cancer and modulate viral infection; Project 3) to study the replication and inheritance of herpesviral genomes in relevant cell types using novel approaches for live cell imaging; Project 4) to characterize cellular and viral factors that regulate the switch from the latent to lytic viral state of Epstein Barr virus (EBV); and Project 5) to define drivers of EBV- associated carcinogenesis and develop novel approaches for treating these cancers and diseases caused by herpesviruses. There are three cores to this PPG that provide expertise in A) administration, statistics and bioinformatics, B) instrumentation, microscopy and histology, and C) virus engineering and production. These cores will be funded during this no cost extension period from institutional support as indicated in the cover letter.

项目摘要/摘要 病毒大约引起人类癌症的15％。人类癌症的病毒病因可以具有实质性 对治疗和预防的后果。例如，许多病毒引起的人类癌的病毒表达 编码产品，是抗病毒，肿瘤特异性疗法的潜在靶标。此外，独特的集合 细胞基因和途径有助于病毒相关的癌症，其中许多目前正在追求 作为抗癌疗法的靶标。该计划项目赠款（PPG）有两个主要目标：使用分子 生物学和遗传学阐明人类肿瘤病毒的生命周期和转化的生命周期并翻译 对特定抗病毒，抗肿瘤疗法靶标的鉴定的理解。我们专注于 研究三种不同病毒家族中的人类肿瘤病毒：乳头瘤病毒，爱泼斯坦Barr病毒和Kaposi 肉瘤病毒。这三个病毒家族共同导致许多病毒相关的人类癌症。 该要求提供5个月的桥梁资金的要求，直到竞争性 续签于2024年初资助是为了支持当前PPG的5个项目中的4个（遗漏的一个项目已有 由于项目2的项目负责人Dan Loeb博士已退休，因此被日落之情。四个项目的目标 是：项目1）识别和表征驱动与人乳头瘤病毒相关的癌症和的细胞基因 调节病毒感染；项目3）研究相关的疱疹病毒基因组的复制和遗传 使用新型方法进行活细胞成像的细胞类型；项目4）表征细胞和病毒因素 调节爱泼斯坦巴尔病毒（EBV）的潜在病毒状态的转换；和项目5）定义驱动程序 与EBV相关的癌变，并开发了治疗这些癌症和疾病的新方法 由疱疹病毒引起。该PPG有三个核心，可以在a）管理，统计数据中提供专业知识 和生物信息学，b）仪器，显微镜和组织学，以及c）病毒工程和生产。 这些核心将在此期间从机构支持的无需延长期间资助，如 求职信。