SPECIFICITY AND MODULATION OF VIRUS INDUCED MEMORY CELLS

我是一名医生，不仅对病人的护理， 转向医学研究，我的护理历史很好地证明了这一点。 我 在北卡罗来纳州哈利法克斯的达尔豪西大学获得医学博士学位。 这段时间我 作为一名医学生，我已经积极参与了内分泌研究 共出版3本。 我继续去拿我的内科药 在同一个机构培训。其次是专科培训， 传染病在加拿大领先的中心在大学 马尼托巴，温尼伯，MB.. 加拿大医学研究理事会资助 我追求我对人类免疫防御的兴趣，并获得了博士学位， 马尼托巴大学医学微生物学系。 我的论文 工作集中于人类NK和γ δ T细胞对肿瘤的反应。 我觉得 进一步训练对病毒的免疫反应， 补充了我的临床和研究兴趣。 我加入了博士。 Raymond Welsh实验室，病理科，马萨诸塞州大学医学 中心，3年前进行博士后培养。 与威尔士医生合作， 这让我做出了一些新的观察，这些观察不仅与病毒有关， 免疫学，但基本的免疫理论。 我已经证明了急性病毒 感染，产生细胞毒性T淋巴细胞（CTL）与 小鼠体内的异源病毒。 异源病毒感染可以引发 CTL应答并提供对第二种病毒的保护性免疫 第二次病毒感染后，记忆CTL 对第一个病毒的反应被部分删除。 我想象一个 记忆细胞的免疫网络，由于有时远程 交叉反应，不断地被传染因子调节 和环境抗原。 我在这里建议使用几种病毒， 合成病毒肽，以探索病毒诱导的特异性 多克隆CTL激活，并确定 交叉反应性CTL在“天然”抗感染和病毒诱导 免疫病理学 具体目标：#1将定义病毒的动力学 CTL对LCMV应答的肽特异性; #2分析CTL 不同病毒之间的反应交叉反应; #3测试模型系统 交叉反应的重要性 这是一个理想 环境，以实现我的临床研究者的最终目标。 内 博士威尔士的实验室我可以继续发展强大的基础科学背景 在病毒免疫学领域，在一所学校， 病毒免疫学跨部门项目 随着我工作的进展， 有潜力与哈里特博士 罗宾逊博士将我的模型应用于她在猕猴体内的艾滋病毒系统。 弗兰克·恩尼斯，研究人类感染病毒的免疫调节 例如流感、HIV和EBV。

I am a physician with a strong commitment not only to patient care but also to medical research , which is well demonstrated by my carer history. I obtained m MD at Dalhousie University, Halifax, N.S.. During this time I was already actively involved as a medical student in endocrine research resulting in 3 publications. I went on to obtain my internal medicine training at the same institution., followed by subspecialty training in infectious diseases at the leading Canadian center at the University of Manitoba, Winnipeg, Mb.. With Medical Research Council of Canada funding I pursued my interest in human immune defenses and obtained a PhD, in the medical Microbiology Department at the University of Manitoba. My thesis work focused on human NK and gammadelta T cell responses to tumors. I felt that further training with immunological responses to viruses would complement both my clinical and research interests. I therefore joined Dr. Raymond Welsh's Lab, Pathology Dept., University of Massachusetts Medical Center, 3 years ago for postdoctoral training. Working with Dr. Welsh, has led to my making some novel observations which pertain not only to viral immunology but to basic immuno theory. I have shown that acute viral infections, generate cytotoxic T lymphocytes (CTL) cross-reactive with heterologous viruses in mice. A heterologous viral infection can prime a CTL response and provide some protective immunity to a second viral infection, and subsequent to the second viral infection, the memory CTL response to the first virus becomes partially deleted. I envision an immunological network of memory cells that, by virtue of sometimes remote cross-reactivities, are continually being modulated by infectious agents and environmental antigens. I propose here to use several viruses and synthetic viral peptides to explore the specificities of virus-induced polyclonal CTL activation and to determine the significance of crossreactive CTL in "natural" resistance to infection and virus-induced immunopathology. Specific Aims: #1 will define the kinetics of the viral peptide specificities of the CTL response to LCMV; #2 analyzes CTL responses crossreactive between different viruses; #3 tests model systems for the significance of the crossreactive responses. This is an ideal environment to achieve my ultimate goal of clinical investigator. Within Dr. Welsh's Lab I can continue to develop a strong basic science background in the field of viral immunology, at a school that has a strong interdepartmental program in viral immunology. As my work progresses I have the potential to form collaborative efforts with both Dr. Harriet Robinson, applying my models to her HIV system in macaques, and with Dr. Frank Ennis, looking at immune modulation in human infections with viruses such as influenza, HIV and EBV.