CYTOTOXIC T LYMPHOCYTE RESPONSE TO HPV 16

描述：(申请人的描述)医学博士学位学生。 在阿尔伯特爱因斯坦医学院的项目中，中川博士研究了 小鼠主要组织相容性复合体的结构与功能关系 就其免疫学和生理学特性而言。之后 在华盛顿大学完成实验室医学住院医师计划 在加州的旧金山，她仍然在那里，她开始了一项研究 人乳头瘤病毒16型细胞免疫研究项目 (HPV16)，它是宫颈不典型增生和癌症的病原体。数据 到目前为止收集的，使用T细胞增殖试验以及 细胞毒性淋巴细胞检测，支持她的工作假说 对HPV的细胞免疫有助于消除HPV，因此 预防相关疾病的发展。这些实验 本申请中提出的建议与正在进行的纵向研究嵌套在一起 其中HPV16感染未发展为高级别的妇女 对上皮内病变进行细胞毒性T淋巴细胞反应测试 HPV16癌基因蛋白、E6和E7。这个项目的具体目标是 为了表征负责抗HPV活性的淋巴细胞亚群(S)， 消除本底活度，探索体外替代方法 刺激，并开发一种方案来执行细胞毒性T淋巴细胞 用T细胞系代替批量培养进行检测。最后的目标将会给你 美国未来将成为识别HPV16免疫优势表位的工具。这个 该项目的长期目标是开发有效的疫苗和 预防和治疗宫颈癌的免疫疗法。 中川博士的长期职业目标是继续研究HPV 免疫学作为一名独立的调查者。她预想这将是最好的 通过成为学术医学中心的教员完成的 在那里她还将作为一名实验室医学承担临床责任 医生。加州大学旧金山分校，这是一个专业 拥有众多杰出科学家的学术医疗机构，提供 良好的环境来发展她的技能和进一步发展她在 来实现她的目标。

DESCRIPTION: (Applicant's Description) As a student in an M.D.-Ph.D. program at Albert Einstein College of Medicine, Dr. Nakagawa studied the structure function relationships of murine Major Histocompatibility Complex in terms of its immunological and physiological properties. After completing a residency program in laboratory medicine at the University of California at San Francisco, where she still is, she began a research project studying cell-mediated immunity to Human Papilloma Virus type 16 (HPV 16) which is a causative agent of cervical dysplasia and cancer. Data collected thus far, using a T cell proliferative assay as well as a cytotoxic lymphocyte assay, support her working hypothesis that cell-mediated immunity to HPV is instrumental in its elimination and thus is protected against the development of associated diseases. The experiments proposed in this application are nested with an ongoing longitudinal study in which HPV 16 infected women who have not developed high grade intraepithelial lesions are tested for cytotoxic T lymphocyte responses to HPV 16 oncogenic proteins, E6 and E7. The specific aims of this project are to characterize the lymphocyte subset(s) responsible for anti-HPV activity, to eliminate background activity, to explore alternative methods of in vitro stimulation, and to develop a protocol to perform cytotoxic T lymphocyte assay using T cell lines instead of bulk cultures. The last aim will give us a tool to identify immunodominant epitopes of HPV 16 in the future. The long-term goal of this project is to develop effective vaccines and immunotherapy for prevention and treatment of cervical cancer. Dr. Nakagawa's long-term career goal is to continue research in HPV immunology as an independent investigator. She envisions this will be best accomplished by becoming a faculty member at an academic medical center where she will also have clinical responsibilities as a laboratory medicine physician. The University of California at San Francisco, which is a major academic medical institution with many distinguished scientists, offers an excellent environment to develop skills and further her expertise in the field to accomplish her goals.