# Characterization and Modulation of Caspase 4-Mediated Pyroptosis

> **NIH NIH F32** · STANFORD UNIVERSITY · 2021 · $68,562

## Abstract

Project Summary/Abstract
 The innate immune system is the first-line of defense against both endogenous and exogenous threats, serving
dual roles as both effectors and activators. However, when the innate immune system responds too robustly to a stimulus,
this can lead to the host’s demise, a phenomenon we frequently call “sepsis”. Sepsis is frequently associated with
infection by a gram-negative bacterial agent such as E. coli or P. aeruginosa and has been hypothesized to be driven by
their immunogenic substances, with lipo-polysaccharide (LPS) likely playing a critical role in this aberrant over-signaling.
This proposal outlines a plan to study the intracellular receptor of LPS, a recently discovered phenomenon seemingly the
cause of endotoxemia, although the mechanisms underlying the exact nature of this receptor are still unknown. By probing
both the enzyme’s activation and characterizing its downstream proteolytic events, we plan to identify if this receptor is
the root cause of LPS-induced shock in human cell systems, as knockout of its murine homolog is protective against
endotoxin shock when directly injected into mice. In addition to further characterizing the basic nature of this intracellular
LPS receptor, we will initiate a screening campaign to identify selective molecules with a preference for this enzyme, over
its closely related family members. The data generated by this proposal should identify either a validated therapeutic
target for the reversal of sepsis and septic shock, a biomarker for the proper diagnosis of sepsis, or a new, highly sensitive
assay for the detection of endotoxin in serum.

## Key facts

- **NIH application ID:** 10239081
- **Project number:** 5F32GM134689-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Joseph Anthony Buonomo
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $68,562
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10239081

## Citation

> US National Institutes of Health, RePORTER application 10239081, Characterization and Modulation of Caspase 4-Mediated Pyroptosis (5F32GM134689-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10239081. Licensed CC0.

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