Human Papillomavirus and Polyomavirus Associated Malignancies.

人乳头瘤病毒和多瘤病毒相关恶性肿瘤。

• 批准号: 9389980
• 负责人: DENISE A. GALLOWAY
• 金额: $ 49.72万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9389980
• 关键词: Address; Data; Diagnosis; Environment; Epidemiologist; Fibroblasts; Goals; Human; Human Activities; Human Papilloma Virus Vaccine; Human Papillomavirus; Human papilloma virus infection; Immune response; Infection; Laboratories; Lead; Malignant Neoplasms; Merkel Cells; Modeling; Mutation; Natural History; Oncoproteins; Other Genetics; Play; Polyomavirus; Polyomavirus Infections; Primates; Proteins; Reagent; Rodent; Role; Small T Antigen; Telomerase; Testing; Tumorigenicity; Vaccination; Vaccines; Viral; Viral Oncogene; Virus; base; experience; inhibitor/antagonist; innovation; insight; long term memory; mouse model; novel; novel therapeutics; prevent; response

PROJECT SUMMARY/ABSTRACT My laboratory has been a leader in taking a broad based approach to studying the role that human papillomaviruses (HPVs) and human polyomaviruses (HPyVs) play in cancer. A major focus has been mechanistic studies to elucidate the contributions of the viral oncoproteins to malignancy. We have identified novel activities of the HPV E6 and E7 proteins including the induction of telomerase activity and inactivation of the p21 CDK inhibitor. For Merkel Cell polyomavirus (MCPyV) we have shown that it defines a new clade of PyVs that contains both primate and rodent PyVs encoding Middle T like proteins. We will explore new data showing that the Small T antigen can transform primary human fibroblasts and cooperate with Ras. We will develop novel mouse models to determine other genetic alterations that cooperate with the viral oncogenes to promote tumorigenicity. These models will be used in innovative ways to test new therapies. Additionally we have led, and participated in, collaborative studies with epidemiologists, statisticians and clinicians to understand the natural history of HPV infections and the host immune response to infection or vaccination. Our current studies focus on understanding the long term memory response to HPV infection to develop better insights into the mechanism of protection of the highly efficacious HPV vaccines, as well as to answer translational questions about optimal vaccine usage. Our overall goal has been, and will continue to be, to find new ways to better prevent, diagnose and treat HPV and HPyV infections that can lead to cancer. We are addressing significant issues, have a proven track record, a wealth of experience and reagents, terrific collaborators and an outstanding environment.

项目摘要/摘要 我的实验室一直是采取广泛的方法来研究人类角色的领导者 乳头瘤病毒（HPV）和人类多瘤病毒（HPYV）在癌症中发挥作用。重点是 机械研究以阐明病毒癌蛋白对恶性肿瘤的贡献。我们已经确定了 HPV E6和E7蛋白的新活性，包括诱导端粒酶活性和失活 P21 CDK抑制剂。对于默克尔细胞多瘤病毒（MCPYV），我们表明它定义了一个新的进化枝 PYV既包含灵长类动物和啮齿动物PYV，又包含编码中间T的蛋白质。我们将探索新数据 表明小的T抗原可以转化原代人成纤维细胞并与RAS合作。我们将 开发新型小鼠模型，以确定与病毒癌基因合作的其他遗传变化 促进肿瘤性。这些模型将以创新的方式用于测试新疗法。另外我们 与流行病学家，统计学家和临床医生一起领导并参加了合作研究 了解HPV感染的自然病史以及对感染或疫苗接种的宿主免疫反应。 我们目前的研究着重于了解对HPV感染的长期记忆反应以更好地发展 了解保护高效的HPV疫苗的机制，并回答 有关最佳疫苗使用情况的翻译问题。我们的总体目标一直是并且将继续是 更好地预防，诊断和治疗可能导致癌症的HPV和HPYV感染的新方法。我们是 解决重大问题，具有可靠的记录，丰富的经验和试剂，很棒 合作者和杰出的环境。