Infections are the most common cause of death worldwide and no significant improvements in the treatment of severe infection have been developed since the discovery of antibiotics almost a century ago. The role that genetics play in severe infections has not previously been widely investigated. Sepsis is an illness where the patient’s tissues and organs are damaged by the body’s own immune response to infection, and is often life-threatening. Sepsis can lead to septic shock when blood pressure drops and fluid replacement does not improve the condition.
The aim of this project is to explore various ways genetics and epidemiological exposures contribute to sepsis and septic shock. Some of the questions we will be exploring include:
– Do cholesterol-related exposures and their regulatory genetic variants affect survival of sepsis and septic shock patients?
– Are there unique types of sepsis patients? Are there unique types of organ-specific sepsis damage? What can we learn from combining exposure data with genetic and clinical data about organ dysfunction in sepsis? Are there exposures that point to treatment of both organ-specific (e.g., kidney, brain) damage due to sepsis and sepsis and septic shock generally?
– What role do these exposures and their regulatory genetic variants have in differentiating classes of patients? What role do they play in differentiating subclasses (classes of organ dysfunction) in sepsis?
– Are cholesterol-specific exposures enriched in most, if not all, sepsis classes and subclasses? Given the abundance of cholesterol-modulating drugs on the market, can we use any of these existing drugs to be repurposed in sepsis or organ-specific damage in sepsis?
Findings of this project could lead to new treatments for sepsis and septic shock and reduce the death toll caused by these illnesses.