The overarching goal of this midcareer investigator award in patient-oriented research is to expand training in clinical multidisciplinary research focused on environmental health at Yale University. The candidate, Carrie A. Redlich, MD, MPH, an Associate Professor of Medicine, is a well respected clinical investigator with unique training and research experience in multidisciplinary environmental/occupational health research. This proposal will enable Dr. Redlich to expand her current research efforts and to develop a mentoring program that focuses on environmental and occupational health (EOH), and integrates laboratory, clinical and epidemiologic approaches (also known as biomarker research, molecular epidemiology, or translational research). The proposed research project is a continuation of Dr Redlich's ongoing research. Specific aims are: 1) Characterize exposure and host factors which determine/modify risk of isocyanate asthma in a field epidemiologic study of HDI exposed autobody shop workers; 2) Determine how best to diagnose isocyanate asthma and how prevalent it is in autobody shop industry; 3) Investigate the mechanisms by which isocyanates cause isocyanate asthma; 4) Based on T cell or other immunologic responses, identify peripheral blood markers of immune sensitization or isocyanate asthma; 5) Develop a murine model of HDI asthma with the salient features of human isocyanate. The goals of the mentorship program are to provide research mentorship in patient-oriented environmental health research to occupational and environmental medicine fellows, doctoral and postdoctoral students, medical students and other trainees. The program will include didactic training, including new courses in biomarker research, a research infrastructure (data analysis, research assistance, information systems), and hands-on well supervised research mentorship. The environment for EOH research at Yale, spanning clinical, public health, and basic science departments, provides an ideal setting for multidisciplinary collaborative environmental health research and training.