The broad and long term objectives of this research application focuses on rapid biodosimetry and mitigation of radiation injury as well as advancing education in this area. Many individuals believe that the single greatest threat to America is nuclear proliferation and the possibility of a nuclear device detonation on American soil. This center grant application will address the medical needs that would arise should such an event occur. Each program is led by a team of internationally renowned investigators. Many of the principal investigators have a long history of studies on normal tissue responses to radiation injury. While some project PIs are not radiation scientists, the organization of the Center is such that broad based expertise is drawn from all aspects of radiation sciences. Eminent faculty in the areas of radiation biology, radiation oncology and physics are leaders and active participants in this center. This organization provides an infrastructure that brings experts outside the field of radiation sciences into the center in a way that will maximize the likelihood that they will be successful in developing therapies or diagnostics pertinent to the tasks at hand. These investigators have united to form a comprehensive, inclusive, inter-institutional, and interdisciplinary Center for Medical Countermeasures against Radiation (CMCR). The overarching themes are those of: 1) Novel biodosimetry methods for rapid screening, 2) Mitigation of normal tissue injury with focus on: a.) the immune system, b.) lung, c.) gastrointestinal tract and, d.) hematopoiesis. Thus, the broad scientific specific aims are as follows: Aim 1: To develop diagnostic tests for rapid and effective biodosimetry based on optically stimulated luminescence and on DNA based arrays. This will be accomplished by support of work in Program 1. Aim 2: Development of novel, safe and effective drugs or candidate molecules for mitigation of radiation injury. This aim will be accomplished through work on Programs 2 and 3. Aim 3: Development of novel, safe and effective drugs or candidate molecules for enhancing immune recovery following exposure to radiation. This will be accomplished under Program 4. All the cores of the center will support the work to achieve the deliverables for Aim 1, 2 and 3. Equally important is the expertise of this group of investigators who are committed to an educational program to train young investigators in this difficult area. These aims fully support the mission of identifying and developing deliverables that will mitigate the effects of exposure to irradiation while following the NIH roadmap.