Impact of sex on respiratory response to wood smoke exposure

项目摘要/摘要

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.