What drives initiation and severity of sepsis?

Sepsis is a deleterious immune response to infection that leads to life-threatening organ failure and is one of the leading causes of death in the intensive care unit (ICU). Though it has plagued humanity for thousands of years, sepsis is a complex biological scenario that makes it inherently difficult to study, and even more difficult to diagnose and treat in the clinic. The long-term goal of the Napier Lab is to identify and manipulate specific host factors that initiate and drive sepsis severity and mortality. We use our strong expertise in innate immunity, inflammation, and bacterial infections to probe host factors that may drive sepsis.

 

How does the Westernized diet influence immunity?

Recent studies have shed light on the role of diet in regulating the immune system and associated inflammatory diseases. Specifically, the Western Diet, a diet that arose nearly 10,000 years ago during the Neolithic period that is low-fiber and high in saturated fats and sugars, is one of the most prevalent diets in Westernized nations and is associated with more severe inflammatory diseases. Our lab studies the effect of this diet on reprogramming the immune system and altering sepsis outcomes.

Mice on a specialized diet.

Mice on a specialized diet.

Special diet mouse condos.

Special diet mouse condos.

 

What genes regulate inflammatory cell death?

Cell death and release of proinflammatory mediators contribute to mortality during infection and septic shock. Specifically, caspase-11-dependent cell death contributes to pathology and decreases in survival time in sepsis models and some infection models. We used a myriad of techniques, including CRISPR-Cas9 gene editing systems, to identify new proteins and pathways that contribute to caspase-11-dependent cell death during septic conditions and bacterial infection.