Integration of physiopathogenomics to identify progression of illness & stage‐appropriate therapeutic targets in a model of staphylococcal enterotoxininduced lethal shock.

The onset of irreversible shock upon exposure to certain pathogens can progress rapidly from onset of flu‐like symptoms to near‐untreatable illness. Our approach has been to characterize host responses, an approach that offers other benefits that include assessment of “progression of illness”. This can take into account not only time post‐exposure, but also exposure level and susceptibility due to personal factors. Our studies have characterized host gene expression responses to biological threat pathogenic agents as well as to common influenza and other flu‐like pathogens in order to gain an understanding of host responses that lead to irreversible, critical illness. These studies integrate the clinical pathophysiological findings with host‐omics, from 1–72 h post‐exposure, developing algorithms to correlate these massive datasets with the progression of illness and identification of early indicators of impending vascular leakage and eventual collapse. Definition of the biosignatures at various stages during the progression to lethality have revealed stage‐appropriate therapeutic targets have the potentialo to be used for intervention strategies.