Molecular Genetics of Human Papillomavirus Infection and Oncogenesis

人乳头瘤病毒感染和肿瘤发生的分子遗传学

• 批准号: 7465907
• 负责人: PAUL F. LAMBERT
• 金额: $ 25.06万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7465907
• 关键词: Anogenital cancer; Binding; Biological Markers; Cells; Cervical; Clinical; Development; Diagnosis; Disease; Funding; Gene Expression; Gene Expression Profiling; Genes; Goals; Head and Neck Cancer; Human; Human Genetics; Human Papillomavirus; Human papilloma virus infection; Individual; Infection; Laboratories; Lesion; Life Cycle Stages; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Mediating; Molecular; Molecular Genetics; Nature; Numbers; Oncogenes; Papillomavirus; Premalignant; Program Research Project Grants; Progressive Disease; Research Project Grants; Research Proposals; Role; Sampling; Satellite Viruses; Staging; Tumor Virus Infections; Viral; Viral Physiology; Virion; Virus Diseases; carcinogenesis; defined contribution; human papilloma virus oncogene; mouse model; novel; outcome forecast; particle; response; tissue culture; tumor progression; tumorigenesis; validation studies; virus host interaction

Human papillomaviruses (HPVs) are associated with a number of human malignancies including cervical cancer, other anogenital cancers, and a subset of head and neck cancers. The goals of this research project are to continue to further define and understand the viral functions and virusrhost interactions that mediate HPV-associated.disease, from the point of infection to development of HPV-associated malignancy. Over the current funding period, the laboratories of Drs. Lambert and Ahlquist have made a number of important contributions to our understanding of HPV-associated disease, with the development of novel mouse models for HPV-associated. malignancy, gene expression profiling of HPV-associated human cancers, identification of useful biomarkers for HPV-associated cancers, development of a highly efficient means for producing HPV virion particles and its use in studies evaluating host interactions in early stages of HPV-infection, and studies on the individual roles of HPV genes in the viral life cycle. In this new project, Drs. Lambert arid Ahlquist together will characterize the nature and mechanisms of virus:host interactions in the context of HPV infections and HPV-associated malignancy. The specific aims are: (1) to investigate virahhost interactions in the early steps of viral infection (i.e., binding, entry and establishment); (2) to define for mechanistic and epidemiological analysis the changes in human gene and microRNA expression that characterize each stage in the long progression from HPV infection to cervical cancer; and (3) to further characterize mouse models for HPV-associated cervical cancer and to use these mouse models to investigate the role of particular cellular genes, including those identified in Aim 2, in cervical cancer. As in all other projects of this program-project grant, the results should have significant implications for diagnosis, prognosis, and/or therapy of persistent tumor virus infection and virus-associated cancers.

人乳头瘤病毒 (HPV) 与许多人类恶性肿瘤相关，包括宫颈癌 癌症、其他肛门生殖器癌症以及头颈癌的一部分。该研究项目的目标 将继续进一步定义和了解介导的病毒功能和病毒与宿主的相互作用 HPV 相关疾病，从感染到 HPV 相关恶性肿瘤的发展。超过 在当前的资助期间，博士的实验室。兰伯特和阿尔奎斯特做出了许多重要的贡献 随着新型小鼠模型的开发，对我们对 HPV 相关疾病的理解做出了贡献 对于 HPV 相关的。恶性肿瘤、HPV 相关人类癌症的基因表达谱、鉴定 HPV 相关癌症的有用生物标志物，开发高效的生产方法 HPV 病毒粒子及其在评估 HPV 感染早期阶段宿主相互作用的研究中的应用，以及 研究 HPV 基因在病毒生命周期中的个体作用。在这个新项目中，博士。兰伯特干旱 阿尔奎斯特将共同描述病毒的性质和机制：在以下情况下宿主相互作用： HPV 感染和 HPV 相关恶性肿瘤。具体目的是：（1）调查virahhost 病毒感染早期步骤中的相互作用（即结合、进入和建立）； (2) 定义为 机制和流行病学分析人类基因和 microRNA 表达的变化 描述从 HPV 感染到宫颈癌的漫长发展过程中的每个阶段的特征； (3) 进一步 表征 HPV 相关宫颈癌的小鼠模型，并使用这些小鼠模型 研究特定细胞基因（包括目标 2 中确定的基因）在宫颈癌中的作用。如在 该计划项目赠款的所有其他项目，其结果应对诊断具有重大影响， 持续性肿瘤病毒感染和病毒相关癌症的预后和/或治疗。