Impact of sex on respiratory response to wood smoke exposure

项目概要/摘要 这个职业发展建议的重点是获得必要的技术研究和专业知识， 建立一个独立的、由校外资助的研究项目的技能，该项目的重点是调查性别特异性 空气污染物对呼吸系统健康的影响。这项工作建立在我目前的研究，重点是 空气污染物，如木材烟雾，臭氧，烟草制品和电子烟对上呼吸道的影响， 特别是鼻粘膜。这个TIEHR职业发展奖将拓宽我的技术研究 技能和建立下气道评估所需的专业知识，以有效地建立我的独立事业， 吸入毒理学家 这项研究的目的是为了验证一个中心假设，即遗传和激素 性介导木材烟雾暴露呼吸免疫反应。该补助金的目的包括：1） 测定木材烟雾暴露在体内的性别特异性肺生理学和免疫效应，以及2） 评估木材烟雾和性激素操作对原代肺上皮细胞的体外相互作用 和巨噬细胞培养物。完成这项资助所产生的数据将填补知识的巨大空白 了解性别对空气污染物暴露的呼吸反应，特别是对木材烟雾的反应。 它还将开始确定遗传和激素调节气道免疫反应的机制。 在全球范围内，这项工作将为预防或治疗措施提供新的探索目标， 对空气污染物的不良反应。 为了完成我的培训，这项资助联合了多位专家，协同支持研究的目标， 职业培训。目的是实现培训：1）临床研究，2）呼吸功能 评估，3）木材烟雾化学表征，4）下气道采样和样品分析 技术，和5）基因组分析管道，以确定木材烟雾的综合影响 暴露在下呼吸道这项培训将提高我系统地调查性别特异性的能力。 免疫系统的调节和人体临床研究中对空气污染物暴露的反应。培训 每个领域将由各自领域的专家提供。此外，实验室管理， 将通过以下方式获得专业知识、科学沟通、指导和职业发展技能 研讨会、演讲和其他实践培训。在成功完成培训部分后， 这个补助金，预计我将成功地作为一个独立的调查员，并准备建立一个 R 01资助的研究项目。

PROJECT SUMMARY / ABSTRACT This career development proposal is focused on acquiring the necessary technical research and professional skills to establish an independent extramurally funded research program focused on investigating sex specific effects of air pollutants on respiratory health. This work builds on my current research, which focuses on the effects of air pollutants such as wood smoke, ozone, tobacco products, and e-cigarettes on the upper airway, specifically in the nasal mucosa. This TIEHR career development award will broaden my technical research skills and build needed expertise in lower airway assessment to effectively establish my independent career as an inhalation toxicologist. The research proposed in this grant is designed to test the central hypothesis that that genetic and hormonal sex mediate respiratory immune responses to wood smoke exposure. The aims of this grant include: 1) determining sex specific pulmonary physiology and immune effects of wood smoke exposure in vivo and 2) evaluating ex vivo interactive effects of wood smoke and sex hormone manipulation on primary lung epithelial and macrophage cell cultures. Data generated by the completion of this grant will fill a large gap in knowledge and understanding of sex specific respiratory responses to air pollutant exposure, specifically to wood smoke. It will also begin identifying mechanisms of genetic and hormonal regulation of immune response in the airway. More globally, this work will provide new targets of exploration for preventative or treatment measures against adverse responses to air pollutants. To complete my training, this grant unites multiple experts to synergistically support the goals of research and career training. The aims are designed to achieve training in: 1) clinical studies, 2) respiratory function assessment, 3) wood smoke chemical characterization, 4) lower airway sampling and sample analysis techniques, and 5) genomic analysis pipelines, in order to determine comprehensive effects of wood smoke exposure on the lower airway. This training will enhance my ability to systematically investigate sex-specific regulation of the immune system and responses to air pollutant exposure in human clinical studies. Training in each area will be provided by experts in their respective fields. Additionally, laboratory management, grantsmanship, scientific communication, mentorship, and career development skills will be attained through workshops, presentations, and other hands on training. Upon successful completion of the training portion of this grant, it is expected that I will be successful as an independent investigator and prepared to establish a R01 funded research program.