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

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。环境暴露于空气中的颗粒物与临床上显着的哮喘和呼吸窘迫的急剧增加有关。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浓度以及颗粒物的组成存在变异性。然而，到目前为止，还没有研究试图将这些环境污染物浓度与蛋白质组中可能导致肺部病理生理的生物相关变化联系起来。拟议的项目将通过调查在东北地区城市、农村和人为来源特定监测点收集的空气颗粒物暴露包含独特的成分，从而在肺上皮中产生不同的病理蛋白质谱这一具体假设来满足这一需要。这种不同的影响肺部生物学的能力在新罕布夏州和整个东北部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证据，以帮助政策制定者确定现有标准是否足以保护受影响不成比例的人口，这项研究的具体目标包括识别和量化东北地区不同地点的空气颗粒物。基因组和蛋白质组技术将被用来确定相关浓度的颗粒物对培养中的人上皮细胞的细胞影响。这项工作将支持识别蛋白质生物标记物，然后将其带回人类研究，以证明暴露于空气颗粒物与肺部病理生物学之间的因果关系。这项建议提供了一个机会，以经济有效地评估环境颗粒物1(PM)的浓度和组成，同时还调查暴露和整个州和地区的毒性和可变性的可信机制。

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