Molecular mechanisms and novel therapeutic approaches to combined radiation and b

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DESCRIPTION (provided by applicant): We will investigate combined injury by moderate dose radiation in two models in a two-phase study. In the first phase, we will use anonymized surgical samples irradiated and wounded ex vivo by burning to study gene and protein expression differences, develop a non-invasive assay to predict successful wound healing, and test a beta adrenergic receptor antagonist as potential therapy to improve wound healing. In the second phase, we will investigate similar issues in a mouse model. Thus, the total study will combine human data (which is, however, not in vivo) and data from intact animals (which is in vivo) to obtain relevant information that can inform the development of a better mechanistic understanding of the mechanisms of wound healing in the presence of radiation damage, and to develop potential therapies that can later be tested in the clinic. Public Health Relevance In a nuclear warfare or terrorist incident, combined injury by radiation and burn wounding is likely. We will provide a better mechanistic understanding of the molecular biology behind healing of combined injury wounds, and will test a non-invasive assay for wound healing success and a potential therapy to improve healing. All of this would be of considerable public health benefit in such a scenario.