This proposal outlines a five year training plan culminating in a career in academic pulmonary and critical care medicine. The applicant has completed his subspecialty training, including 18 months of bench research in pulmonary and critical care medicine at the University of California Los Angeles. Through a combination of class work and laboratory training the applicant will further develop his research skills, receive a Ph.D. in Cellular and Molecular Pathology, and become an independent researcher. The training program will focus on the use of transgenic animal models of disease, cell culture systems, and molecular biology to understand the role of iron and anemia in host defense. Tomas Ganz, a pioneer in innate immunity and iron metabolism, will serve as the main scientific mentor. He has trained numerous postdoctoral fellows and graduate students. This program will also involve mentorship from Aldons Lusis, an experienced mouse geneticist, and Robert Strieter, the chief of pulmonary and critical care at UCLA and an expert in inflammatory mediators. Anemia of inflammation (Al) commonly develops during infectious and inflammatory diseases. The iron regulatory hormone, hepcidin, is thought to be the ultimate mediator of Al. Al is often treated with blood products, iron, or erythropoietin despite evidence that iron overload is detrimental in infection and lack of evidence of benefit for routine transfusions in Al. This research will focus on the role of iron and anemia in host defense. Specific aims of this proposal are to determine: 1) the time course of hepcidin upregulation and development of Al during systemic infection;2) whether hepcidin is necessary for the development of Al;3) whether Al contributes to host defense;4) whether hepcidin contributes to host defense by a mechanism independent of Al;and 5) whether supraphysiologic levels of hepcidin are beneficial in systemic infections. The research has broad relevance to the management of Al during severe infections.