Administrative Core

拟议的RESAC中心，题为呼吸效应的银和碳纳米材料，建立在UMDNJ/罗格斯大学和帝国理工学院伦敦之间的长期合作关系。这种关系始于2000-2001年，当时张博士正在帝国理工学院休假。 从那时起，张博士和钟博士，沿着与UMDNJ和帝国理工学院的其他研究人员一起，合作进行了世界上第一项关于哮喘患者在现实世界中暴露于柴油废气颗粒的急性呼吸影响的研究。这项研究产生了一篇开创性的论文，发表在《新英格兰医学杂志》上。Zhang博士、Chung博士和Tetley博士继续合作并制定研究方案，以进一步研究暴露于柴油机尾气颗粒和含有ENM的消费品对心肺影响的病理生理机制。（供资决定待定。 参与RESAC中心提案的UMDNJ/Rutgers研究人员都是新泽西环境与职业健康科学研究所（EOHSI）NlEHS资助的环境暴露与疾病中心（CEED）的成员。CEED的研究人员探索与环境/职业暴露和人类健康之间的多维界面相关的科学问题。这反映在广泛的多学科专业知识（例如，暴露和风险评估、PBPK建模、毒理学、免疫学、生物统计学）。英国合作者提供免费的专业知识（例如，纳米毒理学、肺和细胞生物学、肺医学、纳米材料合成和表征），增强RESAC中心解决当前U19 RFA所要求的关键问题的能力。RESAC中心的组织结构图见图ACI。 RESAC中心由一个行政核心、一个科学核心和三个研究项目组成。此外，该中心还设有一个整合委员会和一个科学咨询委员会。这种组织结构旨在鼓励，最大限度地提高和促进研究项目内部和之间的互动，研究人员之间，以及与通过该RFA建立的NIEHS联盟的其他中心的互动。组织结构旨在以高度集成和协同的方式解决RESAC中心的首要主题：ENM与肺衬里液成分之间的相互作用。我们中心的方法包括使用（1）两种模型ENM，纳米银和碳纳米管，它们的物理化学性质有很大的对比（科学核心），（2）在细胞和分子水平上确定ENM效应和与肺衬里液相互作用的一套体外实验（项目1），（3）一组研究ENM在肺中的结局和生理效应及潜在机制的体内研究（项目2），和（4）计算模型，可以特别适应独特的物理化学在风险定性中确定化学物质的特性（以及随后的毒理学特性）（项目3）。

The proposed RESAC Center, entitled Respiratory Effects of Silver and Carbon Nanomaterials, builds on the long-term collaborative relationship between UMDNJ/Rutgers and Imperial College London. This relationship started in 2000-2001 when Dr. Zhang was spending his sabbatical leave at Imperial College. Since then Drs. Zhang and Chung, along with other researchers at UMDNJ and Imperial College, have collaborated on the world¿s first study of acute respiratory effects of real-world exposure to diesel exhaust particles in persons with asthma. This study generated a seminal paper published in New England Journal of Medicine. Drs. Zhang, Chung, and Tetley have continued to collaborate and developed research proposals to further investigate pathophysiological mechanisms underlying cardio-respiratory effects of exposure to diesel exhaust particles and to consumer products containing ENMs, respectively. (Funding decisions are pending.) The UMDNJ/Rutgers investigators who are part of the RESAC Center proposal are all members of the NlEHS-funded Center for Environmental Exposure and Diseases (CEED) at the Environmental and Occupational Health Sciences Institute (EOHSI) in New Jersey. The CEED researchers probe scientific questions related to the multidimensional interface between environmental/occupational exposure and human health. This is reflected by the wide range of multidisciplinary expertise (e.g., exposure and risk assessment, PBPK modeling, toxicology, immunology, biostatistics) possessed by the CEED members participating in the proposed RESAC Center. The UK collaborators provide complimentary expertise (e.g., nano-toxicology, lung and cell biology, pulmonary medicine, nanomaterial synthesis and characterization), enhancing the capability of the RESAC Center to address critical issues called for by the current U19 RFA. The RESAC Center's organizational chart is shown in Figure ACI. The RESAC Center consists of an administrative core, a scientific core, and three research projects. Additionally, the Center has an Integration Committee and a Scientific Advisory Committee. This organizational structure is designed to encourage, maximize, and facilitate interactions both within and between the research projects, among researchers, and with other centers participating in the NIEHS Consortium established through this RFA. The organizational structure is designed to address, in a highly integrated and synergistic way, the overarching theme of the RESAC Center: the interaction between ENMs and the components of the lung lining fluid. Our Center's approaches involves the use of (1) two model ENMs, nano silver and carbon nanotube, with a large contrast in their physiochemical properties (Scientific Core), (2) a suite of in vitro experiments determining ENM effects and interactions with the lung lining fluid at the cellular and molecular level (Project 1), (3) a set of in vivo studies to study ENM fate in the lung and physiological effects and underlying mechanisms (project 2), and (4) computational models that can specifically accommodate the unique physicochemical (and consequently toxicological) characteristics of ENMs in the characterization of risk (Project 3).