Administrative Core

拟议的RESAC中心，题为银和碳纳米材料的呼吸效应，建立在UMDNJ/Rutgers和伦敦帝国理工学院之间的长期合作关系基础上。这段关系始于2000-2001年间，当时张博士正在帝国理工学院休假。 从那时起，张和钟博士与UMDNJ和帝国理工学院的其他研究人员合作，进行了世界上第一项关于真实世界暴露于柴油废气颗粒物对哮喘患者的急性呼吸影响的研究。这项研究产生了一篇发表在《新英格兰杂志》上的开创性论文 医学。张博士、钟博士和泰特利博士继续合作，并提出研究建议，分别进一步研究接触柴油废气颗粒物和含有ENM的消费品对心血管系统影响的病理生理机制。(融资决定尚未做出。) UMDNJ/罗格斯大学的调查人员是RESAC中心提案的一部分，他们都是新泽西州环境与职业健康科学研究所(EOHSI)NlEHS资助的环境暴露和疾病中心(CEED)的成员。CEED的研究人员探索了与环境/职业暴露与人类之间的多维界面相关的科学问题 健康。这反映在参加欧洲经济共同体的成员拥有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)。 拟建RESAC中心。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、肺部医学、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 组织结构图如图ACI所示。 RESAC中心由行政核心、科学核心和三个研究项目组成。此外，该中心还有一个整合委员会和一个科学咨询委员会。这一组织结构旨在鼓励、最大化和促进研究项目内部和项目之间、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。该组织结构旨在以高度整合和协同的方式处理RESAC中心的总体主题：ENM和肺衬里液体成分之间的相互作用。本中心的方法涉及使用(1)两种模型ENM，纳米银和碳纳米管，它们的物理化学性质差异很大(Science Core)，(2)一套体外实验，在细胞和分子水平上确定ENM的作用以及与肺衬里液体的相互作用(项目1)，(3)一套体内研究，以研究ENM在肺中的去向和生理效应及其机制(项目2)，以及(4)在风险表征中能够特别适应ENM独特的物理化学(和毒理学)特征的计算模型(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 worid's first study of acute respiratory effects of real-worid 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 underiying cardio-respiratory effects of exposure to diesel exhaust particles and to consumer products containing ENMs, respecfively. (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 Occupafional 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 participafing 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 organizafional 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 interacfions 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 underiying 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).