The long-standing focus of our laboratory program involves the radiation and microenvironmental stress response. We have studied the effects of tumor hypoxia and have investigated the role of hypoxia-inducible factor 1 (HIF-1) and hypoxia-inducible factor 2 (HIF-2) in radiation sensitization. A somewhat related set of studies involves the role of non-specific nonsteroidal antiinflammatory drugs (NSAIDs) and cyclooxygenase (COX) inhibitors as radiation modifiers. We are now focusing on "radiation-inducible or suppressible molecular targets" that is, exploring the use of fractionated radiation to induce a cellular phenotype that makes the cell susceptible for molecular targeted therapy. In essence, radiation would set up the tumor for enhanced drug killing. This work is in its early stages. Indirectly related to this work are efforts being done in the Office of the Assistant Secretary for Preparedness and Response in Health and Human Services (HHS). I am heading a group developing civilian medical response planning for radiological and nuclear terrorism and other events. This involves planning, policy, and normal tissue injury-related science. Medical countermeasures are being developed through NIAID support in the Centers for Medical Countermeasures Against Radiation (CMCR). This overall program has major impact to U.S. preparedness and also has a spin-off for normal tissue injury from radiation and the potential for post-exposure mitigators and treatments.