Humans are exposed to ionizing radiation via the environment and through medical interventions, but we know relatively little about the mechanisms by which human cells cope with the physiological stress caused by ionizing radiation. While many studies have examined changes in gene expression that are induced upon exposure of human cells to ionizing radiation, we lack a comprehensive systems-level view delineating which genes interact to coordinate a cellular response to ionizing radiation. In this study, we will examine the dynamic gene regulatory networks mobilized by cells in response to ionizing radiation. We will do so by profiling gene expression of human genes in normal human B cell lines before and at various time points after irradiation. We will analyze the data in a way that permits the identification of gene-gene interactions at various time points. By examining cell lines from unrelated individuals as well as families, we will: (1) infer gene-gene interactions that change in response to ionizing radiation, (2) identify and compare networks of gene-gene interactions at baseline and at various times points after exposure to ionizing radiation, and (3) identify regulatory relationships between genes by integrating results from genetic studies performed in our lab. PUBLIC HEALTH RELEVANCE: Humans are exposed to ionizing radiation in a variety of settings (e.g. radon in the environment, medical x-rays), with some having severe adverse reactions (e.g. cancer). A much needed systems-level understanding of the cellular response to ionizing radiation will allow us to (1) understand how environmental exposures to ionizing radiation may affect humans, (2) generate hypotheses as to why individuals respond differently to ionizing radiation, and (3) determine what we can do to modulate this response.