# Role of NLRP3 signals in ischemia/reperfusion-induced organ injury

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 2022 · $924,366

## Abstract

Project Summary: This proposal evaluates how the cytoplasmic innate immune receptor, NOD-, LRR- and pyrin
domain-containing protein 3 (NLRP3) contributes to chronic kidney disease (CKD) after SARS-CoV2 infection of
human and murine kidneys. The project is highly significant for understanding the steps leading to chronic renal
injury associated with COVID-19 disease.
Broad/long-term objectives: The long-term goals of the proposed research are to define how activation of NLRP3
contributes to chronic injurious tissue responses in human kidneys following SARS-CoV2 infection.
Specific Aims: The central goal of this proposal is to test the hypothesis that SARS-CoV2 infection triggers cell-
type specific responses that affect the NLRP3 pathway, and that dysregulation of this pathway contributes to the
pathogenesis of CKD as a post-acute sequalae of COVID-19 disease.
Research Design and Methods for Achieving the Stated Goals: Aim 1 will examine the effect of SARS-CoV2
infection on NLRP3 pathway activation and its functional consequences in human and murine renal tubular epithelia
and will test consequences of blockade. Aim 2 will examine how SARS-CoV2 infection induces chronic kidney
injury using two murine models of infection, and tests whether blockade of NLRP3 signaling pathways prevents that
injury. Aim 3 will examine the consequences of NLRP3 pathway activation and blockade in SARS-CoV2 chronically
infected human kidney organoids.
Health Relatedness of Project: If the aims of this proposal are met we will learn how activation of NLRP3
contributes to the pathogenesis of the post-acute sequalae of CKD after COVID-19 disease. This knowledge is
crucial for the development of rational target therapies for prevention or amelioration of organ injury following SARS-
CoV2 infection.

## Key facts

- **NIH application ID:** 10555070
- **Project number:** 3R01DK128547-02S1
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Dianne B Mckay
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $924,366
- **Award type:** 3
- **Project period:** 2021-09-24 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10555070

## Citation

> US National Institutes of Health, RePORTER application 10555070, Role of NLRP3 signals in ischemia/reperfusion-induced organ injury (3R01DK128547-02S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10555070. Licensed CC0.

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