DARTMOUTH COL COBRE: P 4: RESPIRATORY EFFECTS OF AIRBORNE PARTICULATE MATTER

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。环境暴露于空气中的颗粒物质已被牵连在临床上显着的哮喘和呼吸窘迫的急剧增加。一些正在进行的监测研究表明，东北地区城市和农村地区的环境和室内颗粒物浓度和成分存在变异。然而，迄今为止还没有研究试图将这些环境污染物浓度与可能导致肺病理生理学的蛋白质组中的生物学相关改变联系起来。拟议项目将通过调查特定假设来满足这一需求，即在东北地区城市、农村和人为来源特定监测点收集的空气颗粒物暴露含有独特的成分，从而在肺上皮中产生不同的病理蛋白质谱。这种影响肺部生物学的差异能力在新罕布什尔州和整个东北地区促进了不成比例的呼吸健康影响。这项工作将提供定性和定量的证据，以帮助政策制定者，因为他们试图确定现有的标准是否足以保护不成比例的受影响的人群，这项研究的具体目标包括识别和量化的空气中的颗粒物在东北地区的各个位置。将使用基因组学和蛋白质组学技术来确定相关浓度的颗粒物对培养的人上皮细胞的细胞效应。这项工作将支持蛋白质生物标志物的鉴定，然后将其带回人体研究，以证明暴露于空气颗粒物和肺病理学之间的因果关系。这项建议提供了一个机会，以成本有效地评估环境颗粒物1（PM）浓度和组成，同时还调查暴露和合理的毒性机制，以及整个国家和地区的变异性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Environmental exposure to airborne particle matter has been implicated in the dramatic increase in clinically significant asthma and respiratory distress. A number of on-going monitoring studies have demonstrated variability in ambient and indoor concentrations and composition of particulate matter in urban and rural areas of the Northeast region. However, no studies to date have attempted to link these ambient pollutant concentrations to biologically relevant alterations in the proteome that may result in pulmonary pathophysiology. The proposed project will address this need by investigating the specific hypothesis that exposure to airborne particles collected at urban, rural and anthropogenic source specific monitoring sites in the northeast region contain unique composition, which produce distinct pathological protein profiles in lung epithelium. This differential ability to affect lung biology promotes disproportionate respiratory health impacts in the State of New Hampshire and across the northeast region. This work will provide qualitative and quantitative evidence to assist policy-makers as they attempt to determine whether existing standards are adequately protective for disproportionately affected populations, The specific objectives of this study include identification and quantification of airborne particulate in various locations across the northeast region. Genomic and proteomic techniques will be used to determine the cellular effects of relevant concentrations of particulate matter on human epithelial cells in culture. This work will support the identification of protein biomarkers that can then be taken back into human studies to prove causal relationships between exposure to airborne particulate and pulmonary pathobiology, This proposal affords an opportunity to cost effectively evaluate the ambient particulate matter 1 (PM) concentration and composition while also investigating exposure and plausible mechanisms of toxicity and variability across the state and reg