Impact of sex on respiratory response to wood smoke exposure

性别对木烟暴露呼吸反应的影响

• 批准号: 10371435
• 负责人: Meghan Elizabeth Rebuli
• 金额: $ 16.12万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-07 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10371435
• 关键词: Address; Adverse effects; Air Pollutants; Air Pollution; Area; Bioenergetics; Biological Response Modifiers; Biology; Biomass; Breathing; Cell Culture Techniques; Cell physiology; Cessation of life; Chemicals; Chronic Obstructive Pulmonary Disease; Clinical Research; Clinical Trials; Communication; Coughing; Data; Development; Disease; Educational workshop; Electronic cigarette; Epithelial; Epithelial Cells; Estrogens; Exposure to; Extramural Activities; Female; Funding; Future; Gene Expression; Gene Proteins; Genetic; Genomics; Goals; Gonadal Steroid Hormones; Grant; Health Policy; Heating; Hormonal; Hormone Receptor; Host Defense; Human; Immune; Immune response; Impairment; In Vitro; Inflammation; Inflammatory Response; Inhalation; Investigation; K-Series Research Career Programs; Knowledge; Laboratories; Link; Lung; Magnetic Resonance Imaging; Measures; Mediating; Mentors; Mentorship; Modification; Ozone; Particulate Matter; Physiological; Physiology; Play; Predisposition; Prevention; Preventive measure; Protein Analysis; Public Health; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary Inflammation; Randomized; Regulation; Reporting; Research; Research Personnel; Respiratory Disease; Respiratory Mucosa; Respiratory physiology; Role; Sampling; Severities; Sex Bias; Sex Differences; Source; Spirometry; Sputum; Structure of mucous membrane of nose; Surface; Techniques; Testing; Training; Viral; Wildfire; Woman; Work; air filter; airway immune response; airway obstruction; analysis pipeline; asthma exacerbation; base; bronchial epithelium; career; career development; cigarette smoke; climate change; cooking; defense response; design; epidemiology study; global health; hormone regulation; immune function; immunoregulation; in vivo; inflammatory marker; macrophage; male; men; novel; particle; particle exposure; pollutant; premature; programs; pulmonary function; respiratory; respiratory health; response; sex; skill acquisition; skills; tobacco products; toxicant; translational model; wood smoke

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.

项目摘要/摘要 这份职业发展建议的重点是获得必要的技术研究和专业知识 建立一个独立的外部资助的研究项目的技能，专注于调查特定的性别 空气污染物对呼吸健康的影响。这项工作建立在我目前的研究基础上，重点是 空气污染物，如木烟、臭氧、烟草制品和电子烟对上呼吸道的影响， 尤其是在鼻黏膜中。TIEHR职业发展奖将拓宽我的技术研究 技能和在下呼吸道评估方面建立所需的专业知识，以有效地建立我的独立职业生涯 吸入性毒物学家。 这项拨款中提出的研究旨在检验核心假设，即基因和激素 性调节对木材烟雾暴露的呼吸系统免疫反应。这笔赠款的目的包括：1) 活体测定木材烟雾暴露的性别特异性肺生理和免疫效应 木材烟雾与性激素干预对原代肺上皮细胞影响的体外研究 巨噬细胞培养。完成这笔赠款所产生的数据将填补知识的一大空白 以及对暴露于空气污染物，特别是木材烟雾的特定性别的呼吸反应的了解。 它还将开始识别呼吸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，这笔赠款联合了多名专家，协同支持研究和 职业培训。这些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)下呼吸道采样和样品分析 技术，以及5)基因组分析管道，以确定木材烟雾的综合影响 暴露在下呼吸道。这次培训将增强我系统调查特定性别的能力 人体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 每个领域都将由各自领域的专家提供。此外，实验室管理， 专业精神、科学交流、指导和职业发展技能将通过以下途径获得 关于培训的研讨会、演示文稿和其他实践。在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。