Small DNA Tumor Viruses and Human Cancer

项目摘要 据预测，病毒会导致近五分之一的人类癌症。麦卡德尔癌症实验室 研究在威斯康星大学麦迪逊分校，研究项目的博士保罗F。兰伯特试图 了解一组特殊的病毒，称为DNA肿瘤病毒，如何导致癌症。一个最 与人类癌症相关的公认DNA肿瘤病毒是人乳头瘤病毒（HPV），它 导致宫颈癌、头颈癌、肛门癌和皮肤癌。25年来，兰伯特博士的实验室 专注于研究HPV相关癌症发展的病毒和细胞机制， 动物模型和专门的组织培养技术。实验室正在应用这些技术 研究最近鉴定的DNA肿瘤病毒默克尔细胞多瘤病毒（MCPyV）及其在 一种罕见的人类皮肤癌 作为兰伯特研究项目的助理科学家，我负责两个主要研究领域：1） 评估HPV、女性激素雌激素和宫颈癌微环境的作用 2）研究MCPyV在人类癌症中的作用。这些研究利用了我的教育 在DNA肿瘤病毒领域的技术培训，以解决新的和重要的科学研究目标。 例如，了解HPV与周围环境相互作用和改变周围环境的方式， 促进癌症发展的微环境将对目前的癌症研究范式产生广泛的影响。 领域我的努力建立在体内模型，使用原发性人宫颈癌样本提供了一个新的研究方向。 前所未有的机会，了解雌激素在人类宫颈癌中的作用，以及一个平台， 探讨使用抗雌激素药物治疗宫颈癌的实用性。此外，继续研究 我帮助开发和表征的MCPyV T抗原表达的小鼠模型将有助于 解决了多瘤病毒如何参与人类癌症的长期疑问。除了我的科学 责任和贡献，我在兰伯特实验室的培训和指导职责有助于 确保其持续增长和成功。在下面的拨款申请中，我的科学和领导角色 在兰伯特研究计划，以及如何这些努力最终支持我们的进步 科学目标，将被描述。

PROJECT SUMMARY Viruses are predicted to cause nearly one fifth of all human cancers. At the McArdle Laboratory for Cancer Research at University of Wisconsin-Madison, the research program of Dr. Paul F. Lambert seeks to understand how a particular group of viruses, called DNA tumor viruses, contribute to cancer. One of the most well-recognized DNA tumor viruses associated with human cancer is human papillomavirus (HPV), which causes cancers of the cervix, head and neck, anus, and skin. For over 25 years, Dr. Lambert’s laboratory has focused on studying the viral and cellular mechanisms involved in HPV-associated cancer development using animal models and specialized tissue culture techniques. The laboratory is now applying these technical approaches to study a recently identified DNA tumor virus, Merkel cell polyomavirus (MCPyV), and its role in a rare form of human skin cancer. As an Assistant Scientist in the Lambert research program, I am directing two main areas of research: 1) evaluating the role of HPV, the female hormone estrogen, and the microenvironment in cervical cancer development, and 2) studying the role of MCPyV in human cancer. These studies make use of my education and technical training in the DNA tumor virus field in order to address novel and vital scientific research goals. For example, understanding the way in which HPV interacts with and modifies the surrounding microenvironment to promote cancer development will have broad implications on current paradigms in the field. My efforts to establish in vivo models using primary human cervical cancer samples provide an unprecedented opportunity to understand the role of estrogen in human cervical cancer, as well as a platform to explore the utility of using anti-estrogen drugs as a cervical cancer treatment. Moreover, continuing studies with a murine model of MCPyV T antigen expression that I helped to develop and characterize will help address a longstanding query of how polyomaviruses are involved in human cancers. Aside from my scientific responsibilities and contributions, my training and mentorship duties within the Lambert laboratory help ensure its continued growth and success. In the following grant application, my scientific and leadership roles within the Lambert research program, as well as how these efforts ultimately support the advancement of our collective scientific objectives, will be described.