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).
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