Impact of sex on respiratory response to wood smoke exposure

项目概要/摘要 该职业发展建议的重点是获得必要的技术研究和专业知识 建立独立的校外资助研究项目的技能，重点调查特定性别 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的基础上，该研究的重点是 木烟、臭氧、烟草制品和电子烟等空气污染物对上呼吸道的影响， 特别是在鼻粘膜中。这个 TIEHR 职业发展奖将拓宽我的技术研究范围 技能并建立下呼吸道评估所需的专业知识，以有效地建立我的独立职业生涯 吸入毒理学家。 这笔赠款中提出的研究旨在检验以下中心假设：遗传和荷尔蒙 性介导对木烟暴露的呼吸道免疫反应。这笔赠款的目的包括：1) 确定体内木烟暴露的性别特异性肺部生理学和免疫影响以及 2) 评估木烟和性激素操作对原代肺上皮的离体交互作用 和巨噬细胞培养物。完成本次资助所产生的数据将填补巨大的知识空白 以及了解对空气污染物暴露（特别是木烟）的性别特异性呼吸反应。 它还将开始确定气道免疫反应的遗传和激素调节机制。 在全球范围内，这项工作将为探索预防或治疗措施提供新的目标 对空气污染物的不良反应。 为了完成我的培训，这笔赠款将多位专家联合起来，协同支持研究和目标 职业培训。目标旨在实现以下方面的培训：1) 临床研究，2) 呼吸功能 评估，3) 木材烟雾化学特性，4) 下呼吸道采样和样本分析 技术，以及5）基因组分析管道，以确定木材烟雾的综合影响 暴露于下呼吸道。这次培训将增强我系统地调查特定性别的能力 人类临床研究中免疫系统的调节和对空气污染物暴露的反应。培训于 每个领域都将由各自领域的专家提供。此外，实验室管理、 资助、科学交流、指导和职业发展技能将通过 研讨会、演示和其他实践培训。成功完成培训部分后 这笔赠款，预计我将作为一名独立调查员取得成功，并准备建立一个 R01 资助的研究计划。

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.