A molecular signature of radiation injury

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In the event of a mass casualty scenario involving radiation exposure due to a terrorist attack, the recovery and outcome of potential victims will depend heavily on the rapid and efficient response of the medical community. Since the effects of radiation are dependent upon time, distance, and shielding from the epicenter of a radiation blast/source, it can be anticipated that exposure levels across an affected population will range from acutely non-significant (e.g. 0-50 cGy), to myelo- and immunosuppressive (100-400 cGy), to potentially life threatening (> 400 cGy). It will be critical, therefore, in such an event, for the medical caregivers to effectively triage which individuals have received a medically deterministic dose versus the "worried well." Unfortunately, in many instances, external dosimetry estimates will not accurately predict the biological exposure that an individual has sustained. Clinical signs of radiation exposure, such as nausea and vomiting, are non specific and could be present in a large number of unaffected individuals secondary to psychogenic stress. Lymphocyte depletion kinetics also require several blood collections over tim e to provide predictive dosimetry information. The gold standard, cytogenetics analysis, also requires several days to complete, during which time valuable therapeutic opportunities may be lost. In this proposal we aim to apply powerful molecular profiling technology to develop a biodosimetry test that can predict different levels of radiation exposure with a high level of sensitivity and specificity. First, we will develop gene expression profiles of normal, low dose-, intermediate dose-, and high dose-irradiated mice. We will then validate those signatures against the molecular profiles of human patients undergoing TBI. Next we will prospectively validate the signatures against unknown samples collected from irradiated mice and humans in a blinded manner. Finally, we will translate this validated molecular profile into a deployable biodosimetric instrument that can be utilized to accurately triage potential radiation victims.