# Cell death proteins as inflammatory mediators in sepsis

> **NIH NIH R35** · EMORY UNIVERSITY · 2024 · $391,250

## Abstract

Sepsis is a significant public health issue in the United States, killing 300,000 people each year and generating
over $60 billion in costs to Medicare beneficiaries. Because we do not fully understand how infection triggers
the inflammatory dysregulation seen in sepsis, no targeted therapies for sepsis are clinically available. Patient
treatments are limited to antibiotics directed against infection and supportive care for organ failure. Cell death
signaling pathways, the mechanisms that control cell fate in response to environmental stimuli, are distributed
throughout mammalian tissue and are a foundational component of host defense against invading pathogens.
During infection, these pathways activate immune responses, clear infected cells, incite tissue damage, and
promote inflammation. This proposal seeks to understand how cell death signaling pathways contribute to the
inflammatory dysregulation that typifies sepsis. This will be done by assaying activity of these pathways under
conditions of infection in both immune and non-immune tissue. Samples collected from septic human patients
will be analyzed for cell death signaling pathway activity and data will be correlated with clinical variables.
Insights gained from these observations will be used to direct mechanistic studies aimed at determining how
these pathways are regulated during sepsis. Both in vitro and in vivo techniques will be utilized when
experiments cannot be performed in human patients. Cultured human cell lines will be infected and analyzed in
vitro, and the effects of cell death signaling pathway inhibition will be measured in septic animals. Results from
this proposal will better define the mechanisms through which infection unleashes dysregulated inflammation in
sepsis and offer a greater understanding of how core cellular homeostasis and defense machinery functions
during critical illness. This knowledge stands to produce novel therapeutic strategies and targets for a deadly
disease process that continues to put tremendous strain on modern healthcare systems.

## Key facts

- **NIH application ID:** 10890077
- **Project number:** 5R35GM151220-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** John Daniel Lyons
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $391,250
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10890077

## Citation

> US National Institutes of Health, RePORTER application 10890077, Cell death proteins as inflammatory mediators in sepsis (5R35GM151220-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10890077. Licensed CC0.

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