REGULATION OF HUMAN PAPILLOMAVIRUSES IN ORAL MUCOSA

候选人卓晨博士目前是一名全职研究助理 德克萨斯大学基础科学系教授 牙科分部，位于德克萨斯州医疗中心，是 世界上最大的医疗保健和研究综合体。陈博士获得了 优秀的生物化学和分子生物学综合培训 从她在路易斯安那州立大学的博士和博士后项目 在进入教职员工之前，这样她就能够快速发展 利用分子技术研究疾病的独立研究项目 在口腔里。1996年，她获得了R29(第一)奖 国家癌症研究所将研究人类的调节 口腔粘膜中的乳头状瘤病毒(HPV)及其调控 在肿瘤细胞中允许过度表达的机制 人乳头瘤病毒转化基因。K02奖将为 帮助她继续将她的背景和在分子方面的培训联系起来 生物学和生物化学对牙科研究，特别是口腔癌的研究。 她将受益于拥有更多的资源和时间来建立更多的 口腔癌发生的综合研究计划 这项研究的结果与她正在进行的其他项目的结果 处理口腔癌中癌基因的过度表达。这是扩展的 Focus将促进并导致制定一项筹资提案 通过RO1机制。她的最终目标是为 更好地理解口腔上皮细胞和口腔组织中的基因表达 癌细胞。拟议的K02项目基于，以及一个 HER R29的延伸以进一步研究为什么口腔上皮细胞 为HPV诱导转化提供了独特的环境。作为 这项研究的第一部分，她发现了功能上的重要意义 口腔癌患者HPV长控制区(LCR)基因突变的研究 细胞。假设细胞蛋白质或它们的复合体是 能够以特定方式作用于突变的LCR以激活 E6和E7癌基因转录，导致恶性 上皮细胞的转化。这项工作将(I)确定和 鉴定主要的细胞蛋白因子和复合体，反式- 正常和恶性HPV-16和HPV-18对E6和E7基因的调控 口腔上皮细胞；(Ii)确定细胞类型的特异性相互作用 HPV LCR和主要调节蛋白因子之间的关系 口腔恶性病变中E6、E7基因表达的激活 上皮细胞；(Iii)描述这些主要细胞之间的相互作用 口腔正常和恶性病变中HPV-16和HPV-18的LCR及其影响因素 上皮细胞。这个项目将增加我们对HPV基因的了解 正常和恶性口腔上皮细胞的调控。此外, 细胞内顺式元件和主要蛋白质的鉴定 人乳头瘤病毒相关口腔癌将提供一个基本的基础 开发潜在的口腔癌症基因治疗策略 空洞。

The candidate, Dr. Zhuo Chen, is currently a full-time research assistant professor in the Department of Basic Sciences at the University of Texas Dental Branch, which is located in the Texas Medical Center which ius the largest medical care and research complex in the world. Dr. Chen acquired excellent comprehensive training in biochemistry and molecular biology from her Ph.D and postdoctoral programs at Louisiana State University before joining the faculty, so that she is able to rapidly develop independent research programs using molecular techniques to study diseases in oral cavity. In 1996, she received an R29 (FIRST) Award from the National Cancer Institute to study the regulation of human papillomaviruses (HPV) in oral mucosa with an emphasis on regulatory mechanisms which function in tumor cells to allow the over-expression of the transforming genes of HPV. A K02 Award would provide the "chain" to help her to continue connecting her background and training in molecular biology and biochemistry to dental research, specifically to oral cancer. She would benefit by having additional resources and time to build a more comprehensive research program in oral carcinogenesis by combining the findings from this research with those of her other ongoing projects dealing with over-expression of oncogenes in oral cancer. This expanded focus will facilitate and lead to development of a proposal for funding via the RO1 mechanism. Her ultimate goal is to provide the basis for a better understanding of gene expression in oral epithelial cells and oral cancer cells. The proposed K02 project is based on, as well as an extension of, her R29 to further investigate why oral epithelial cells provide the unique environment for HPV-induced transformation. As the first part of this study, she has detected functionally significant mutations in the HPV long control region (LCR) isolated from oral cancer cells. The hypothesis is that cellular proteins or their complexes are able to act on the mutated LCR in a specific manner to activate the transcription of the E6 and E7 oncogenes, leading to malignant transformation of epithelial cells. This work will (i) identify and characterize the major cellular protein factors and complexes that trans- regulate E6 and E7 genes from HPV-16 and -18 in both normal and malignant oral epithelial cells; (ii) determine cell-type specific interactions between the HPV LCR and major regulatory protein factors which are responsible for activation of E6 and E7 gene expression in malignant oral epithelial cells; (iii) delineate the interactions between these major factors and the LCR of HPV-16 and-18 in both normal and malignant oral epithelial cells. This project will increase our understanding of HPV gene regulation in normal and malignant oral epithelial cells. In addition, identification of cis-elements and major cellular proteins involved in HPV-related oral cancers will provide a fundamental basis by which to develop potential gene therapy strategies against cancer in the oral cavity.