Systems Biology Approach to Identify Biomarkers and Risk Factors of Heat Injury / Stroke Susceptibility

Heat stroke (HS) is a life-threatening illness induced by prolonged exposure to a hot environment that causes central nervous system abnormalities and severe hyperthermia. There is a critical military medical need to identify biomarkers, risk factors & intervention strategies to decrease heat injury/stroke (HI/S) susceptibility. Current data suggest that the pathophysiological responses to heatstroke may not be due to the immediate effects of heat exposure per se but the result of a systemic inflammatory response syndrome (SIRS) that ensues following thermal injury. Recent evidence suggests that prior infection (viral & bacterial) or prior heat injury increases Warfighter susceptibility to HI/S by deactivating molecular inflammatory mechanisms that protect against multi-organ damage & failure. Exploiting a Systems Biology approach – which focuses on the complex interactions in biological systems – can help to understand the role of cytokines in the thermoregulatory and inflammatory responses to heat stroke. Moreover, we aim to identify biomarkers, risk factors & molecular pathways of increased HI/S susceptibility using rodent HI/S models, military field study of HI/S victims & mathematical modeling of molecular inflammatory pathways. Our experimental collaborator on this project is Dr. Lisa R. Leon, U.S. Army Research Institute for Environmental Medicine (USARIEM).