Preclinical Studies

We developed and validated the gold standard of murine neonatal sepsis modeling: the cecal slurry model of generalized peritonitis (2007). This model permits in-depth mechanistic investigation of the neonatal-specific host immune response to sepsis through the application of pharmacologic and genetic (knock-in, knock-out, and humanized) approaches.

We showed the neonate, in stark contrast to the adult, does not depend on adaptive immunity or type I interferon signaling for a successful host response (2008). In that report, we also demonstrated that innate immune priming (trained immunity) using selected toll-like receptor agonists dramatically reduced subsequent sepsis mortality by up to 40 percent and was associated with enhanced innate immune cellular function.

Recently, we showed murine neonatal CD71+ erythroid cells, although immunomodulatory ex vivo, had no impact on murine neonatal sepsis survival (2015). We showed the deleterious role of IL-18 in neonatal sepsis and is published in the Proceedings of the National Academy of Sciences (2016) and the subject of our NIGMS-funded R01 entitled Modifiable Determinants of Mortality in Neonatal Sepsis (R01HD089939). We showed IL-1α and not IL-1β drives IL-1R1-dependent neonatal murine sepsis lethality, highlighting a potential mechanism behind the inability of anakinra to reduce sepsis mortality (2018)

We are actively investigating other beneficial mechanisms of innate immune stimulation and detrimental mechanisms of sepsis.

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