Mechanisms of Eosinophil Effector Functions in the Lung

基因转移技术的使用和小鼠作为人类呼吸道疾病模型的应用恰当地总结了 研究计划的候选人，詹姆斯（杰米）J-.ee，博士。这项工作构成了候选人的基础 近期的职业目标是扩大他的实验室的广度，包括越来越复杂的评估， 病理学的生理学相关终点。这些近期目标的实现反过来又支持了 长期目标，包括（i）将实验室的方向从分子生物学的角度转变为 （ii）在马约内扩大小鼠研究的教育活动 基金会，特别是亚利桑那州的马约诊所，并包括亚利桑那州立大学的区域研究生课程 大学。梅奥诊所对研究和研究生教育的机构支持和承诺， 与不断扩大的当地大学研究生课程在生物医学研究，代表了独特的 利用鼠标作为人类的模型系统， 疾病研究。本职业发展计划的一个关键目标是招募和培养有动力的学生 和研究员，利用实验室的研究活动的成功。 是为了确定嗜酸性粒细胞和嗜酸性粒细胞效应功能介导过敏性炎症的作用， 因此，它们在肺部病理学发展中的作用。这项提案利用了独特的嗜酸性粒细胞- 我们在嗜酸性粒细胞的研究中创造了特异性试剂和新型转基因和基因敲除小鼠， 生物学这些目标将通过完成以下目标来实现：（1）确定 明确的是，嗜酸性粒细胞对在转基因肺肿瘤模型中出现的肺部病理的贡献。 研究JJL-5和Eotaxin-2共表达对哮喘发病的影响;（2）探讨Eotaxin-2与JJL-5共表达的作用机制 在IL-5/eotaxin-2转基因哮喘模型中引起肺病理学的功能; (3)为了确定脱粒和颗粒蛋白的释放是否代表了一种机制， 嗜酸性粒细胞导致哮喘的IL-5/嗜酸性粒细胞活化趋化因子-2转基因模型中出现的病理。

The use of gene transfer technologies and the mouse as a model of human respiratory diseases aptlysummarizes the research program of the candidate, James (Jamie) J-.ee, Ph.D. This work forms the basis of the candidate's immediate career goals of expanding the breadth of his laboratory to includeincreasinglycomplex assessmentsof physiologically relevant endpoints of pathology. The achievement of these immediate goals, in turn, support the long term goals, including (i) To move the orientation of the lab from a molecular biology perspective to a physiology-based program and (ii)To expand the educational activities in mouse research within the Mayo Foundation, and Mayo ClinicArizona in particular,and to includethe regional graduate program at ArizonaState Uni versity. The institutional support and commitmentto research and graduate education offered byMayo Clinic, together with the expanding local university graduate programs in biomedical research, represent unique opportunities to create a collaborative center of focused efforts using the mouse as a model system of human disease research. A critical objective of this career development plan is to recruit and train motivatedstudents and fellows, capitalizing on the success of the laboratory's research activities.The goals of the researchproposal are to define the role(s) of eosinophils and eosinophil effector functions mediating allergic inflammation and, therefore, their roles in the development of pulmonary pathologies. The proposal exploits unique eosinophil- specific reagents and novel transgenic and gene knockout mice we have created in our studies ofeosinophil biology. The objectives will be achieved through the completion of the following aims: (1) To determine unequivocally the contribution(s)of eosinophils to the pulmonarypathologies arising in a transgenic model of asthma generated by the co-expression of JJL-5 and eotaxin-2; (2) To define mechanisms of eosinophil effector functions responsible for the pulmonarypathologiesoccurring in the IL-5/eotaxin-2 transgenicmodel of asthma; (3) To determine if degranulation and the release of granule proteins represents a mechanism by which eosinophils contribute to the pathologies arising in the IL-5/eotaxin-2 transgenic model of asthma.