Sasha Jemison
Research Mentor(s): Vinitha Jacob
Mentor Department: Emergency Medicine
Authors: Sasha Jemison, Vinitha Jacob
Session: Session 6 (3:00pm – 3:50pm)
Presentation Type: Poster 86
Abstract
Sepsis, defined as the body’s uncontrolled response to an infection, is a common, costly, and deadly disease. Endotoxemia, the presence of components of bacteria in the blood, is a feature of sepsis pathogenesis. Despite advances in antibiotics, sepsis remains resistant to current standards of care and thus carries a high mortality rate. Our project involves identifying novel targets in a zebrafish model to identify potential novel sepsis targets and therapeutics. We employ zebrafish as our model organism because they are vertebrates with a high degree of genetic conservation to humans. Furthermore, zebrafish can produce hundreds of progeny per mating, allowing for high-throughput testing that is impossible in other vertebrates. We first use lipopolysaccharide (LPS), a component of the outer membrane of gram-negative bacteria, to induce endotoxemia in zebrafish and to characterize whether features of human sepsis are replicated. We find that our LPS-induced endotoxemia model recapitulates key elements of human sepsis, including upregulation of the immune response and elements of sepsis-induced coagulopathy, which confirmed commonalities between the pathways induced by LPS in zebrafish and human sepsis. We next perform an in-vivo drug screen in this model using FDA-approved compounds to identify potential therapeutic candidates for human sepsis. We find several candidate compounds that successfully conferred protection from LPS-induced mortality at specific concentrations. However, we find surprising differences in the types of responses induced by LPS from different bacteria, as confirmed by pathway analysis. Consequently, the compounds that block LPS toxicity vary based on the bacteria that they originate from. Our findings have implications for developing therapeutics for human inflammatory conditions, including sepsis.
