January 23, 2020

Dr. Vladimir Badovinac received a five-year NIH MIRA(Maximizing Investigators' Research Award) R35 entitled ‘Cellular and Molecular Mechanisms Controlling Sepsis-induced Immunoparalysis State’ from the National Institute of General Medical Sciences (NIGMS). Five-year MIRA grants are awarded by the NIGMS to productive investigators in order to “take on ambitious scientific projects and approach problems more creatively”.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. It represents a significant public health burden striking 1.7 million American annually (with 20-25% mortality). In general, early stages of sepsis are characterized by a potentially detrimental hyperinflammatory state. However, patients who survive the cytokine storm phase of sepsis enter a state of immunoparalysis defined by enhanced susceptibility to infection, viral reactivation, and mortality years after the septic insult. Sepsis-induced lymphopenia reduces the number of immune cells and influences the function of remaining/surviving cells. Yet, the sepsis-induced lymphopenia is transient while the prolonged immunoparalysis (or immunosuppression) that develops (even after lymphocyte numbers normalize) is now considered a leading reason for the extended period of increased susceptibility to bacterial and viral pathogens normally handled by the immune system in healthy individuals. Therefore, our long-term goal in the next five years is to precisely determine, on cellular and molecular levels, sepsis-induced changes in various lymphocyte populations that support and define the chronic state of immunoparalysis and inability of immune cells to exert their effector functions properly.