Radiation therapy is a commonly used treatment modality for a wide range of oncological problems, including treatment of solid tumors in the primary or metastatic setting and as a conditioning regimen prior to hematopoietic stem cell transplantation. Despite providing excellent clinical response rates, radiation treatments targeting tumors are often limited by the radiosensitivity of nearby normal organs. The goal of our research project is to characterize radiation-induced immune responses and to identify radiomitigating strategies, using in vivo murine and cell culture models. We are studying pro-inflammatory radiation sequelae in several contexts, including following cranial irradiation, in the setting of total body irradiation as part of pre-transplantation conditioning, and in a model of catastrophic radiation injury exposure. Elucidating the molecular mechanisms regulating immune system activation following radiation is a critical step towards developing clinical strategies to either downregulate pro-inflammatory signals leading to damaging sequelae such as brain radionecrosis, or to modulate the inflammatory response to optimize anti-tumor immunity.