REGULATION OF TAP-1 AND MHC-I IN RESPIRATORY PAPILLOMAS

这份由一位年轻的训练有素的耳鼻喉科医生提出的申请旨在 为学术生涯做准备的第一步 临床医生/科学家。这笔赠款将提供正规的学习培训。 设计和实施广泛的研究项目和学术课程 与项目相关的工作。申请者的长期目标是 成为一名多产的研究科学家，在拨款方面具有竞争力 一个临床环境。 培训环境是一家大型教学医院，是一家临床 一所医学院的校园。这家医院提供研究生医疗服务 初级保健和内外科教育项目 特色菜。它拥有一大批从事研究的全职教职员工。 来自联邦和非联邦来源的赠款。申请人的 导师在耳鼻喉科和儿科 过敏/免疫学，是医学院的全职教授。 该研究项目的长期目标是了解 反复呼吸道感染的免疫识别机制 乳头状瘤病，以便更好地管理这种疾病 已实现。具体的目标将检验这样的假设：人类 乳头瘤病毒表达导致TAP-1水平或功能降低 (抗原-1的转运体)和随后的I类MHC组装和 在细胞表面的表达。目标是：1)确定是否 喉乳头状瘤组织中TAP-1和MHC基因和/或蛋白表达降低 组织和培养细胞，与正常组织和细胞相比。2) 确定TAP-1/MHC-I/钙结合蛋白复合体 乳头状瘤细胞的正常功能以及钙是否调节 复合体及TAP-1和MHC-1在正常和正常组织中的表达差异 乳头状瘤细胞。3)确定哪些病毒早期蛋白改变了TAP-1 和MHC-1的表达。4)确定MHC-I水平是否增加 如果TAP-1电平增加或其功能被绕过。

This application from a young trained otolaryngologist is intended as an initial step in preparation for a career as a academic clinician/scientist. The grant will provide formal training in study design and conduct of an extensive research project and academic course work relevant to the project. Long term goals for the applicant are to be a productive research scientist, competitive for grant funding, in a clinical environment. The training environment is a large teaching hospital that is a clinical campus for a medical school. The hospital offers graduate medical education programs in primary care and medical and surgical specialities. It has a large number of full-time faculty with research grants from both federal and non-federal sources. The applicant's mentors are in the Departments of Otolaryngology and Pediatric Allergy/Immunology, and are full professors at the medical school. The long term goal of the research project is to understand the mechanisms of immune recognition in recurrent respiratory papillomatosis, so that better management of this disease can be achieved. The specific aims will test the hypothesis that human papillomavirus expression results in reduced levels or function of TAP-1 (transporter of antigen-1) and subsequently Class I MHC assembly and expression on the cell surface. The aims are: 1) Determine whether TAP-1 and MHC mRNA and/or proteins are reduced in laryngeal papilloma tissues and cultured cells, compared to normal tissue and cells. 2) Determine whether the TAP-1/MHC-I/calcium binding protein complex functions normally in papilloma cells and whether calcium modulates the complex and TAP-1 and MHC-1 expression differently in normal and papilloma cells. 3) Determine which viral early proteins alter TAP-1 and MHC-1 expression. 4) Determine whether MHC-I levels are increased if TAP-1 levels are increased or its function is bypassed.