ADENOSINE RECEPTORS IN ALLERGIC INFLAMMATION

为了成功地进行免疫介导的肺损伤机制的生物医学研究，必须对分子生物学，免疫学和肺生理学的现代技术有扎实的了解。 我在肺部医学方面的培训使我有机会在诊断和治疗各种肺部疾病患者的同时广泛研究肺部生理学。 虽然我已经开始获得分子生物学方面的一些技能，但长期的持续指导培训对于发展追求高质量肺部疾病研究所需的经验和技能至关重要。 Koller博士在研究疾病发病机制的小鼠模型的生成和表征方面的专业知识使她的实验室成为这种指导培训的理想环境。 该项目的总体目标是通过利用小鼠模型来确定腺苷对过敏性气道疾病的贡献，在小鼠模型中，A2b和A3腺苷受体基因的表达已经使用胚胎干细胞中的同源重组被灭活。 具体来说，我们将定义这些受体在免疫细胞和小鼠肺中的表达，确定负责腺苷诱导的肥大细胞脱粒的受体，并确定腺苷激活这些受体对过敏性气道疾病的整体发病机制的意义。 该项目将提供最先进的分子生物学，免疫学和小鼠肺生理学方面的广泛实践培训，该环境将促进独立研究技能的发展，这些技能是调查肺部疾病机制的职业所必需的。

To successfully pursue biomedical research into the mechanisms of immune mediated lung injury, one must have a solid understanding of modern techniques in molecular biology, immunolgy, and pulmonary physiology. My training in pulmonary medicine has given me the opportunity to extensively study pulmonary physiology while diagnosing and treating patients with a variety of lung diseases. While I have begun to acquire some skills in molecular biology, an extended period of continued mentored training is critical for the development of the experience and skills necessary to pursue high quality research into lung disease. Dr. Koller's expertise in the generation and characterization of mouse models to study the pathogenesis of disease makes her laboratory an ideal environment for this mentored training. The overall objective of this project is to determine the contribution of adenosine to allergic airways disease by utilizing mouse models in which the expression of the A2b and A3 adenosine receptor genes have been inactivated using homologous recombination in embryonic stem cells. Specifically, we will define the expression of these receptors on immune cells and in murine lung, determine the receptor responsible for adenosine-induced mast cell degranulation, and determine the significance of activation of these receptors by adenosine to the overall pathogenesis of allergic airways disease. This project will provide extensive hands-on training in state of the art molecular biology, immunology, and murine pulmonary physiology in an environment that will promote the development of independent research skills necessary for a career investigating the mechanisms of pulmonary disease.