# AIM2 as a negative regulator of renal ischemia/reperfusion injury

> **NIH NIH R21** · SCRIPPS RESEARCH INSTITUTE, THE · 2021 · $221,875

## Abstract

Project Summary: This proposal studies how activation of a key cytoplasmic innate immune receptor, the
pattern recognition receptor AIM2, regulates activation of the NLRP3 inflammasome and thus protects from
renal tubular epithelial cell (RTE) injury. The project is highly significant for acute kidney injury, which occurs
frequently and leads to the burden of chronic kidney disease.
Broad/long-term objectives: The long-term goals of the proposed research are to define how activation of
AIM2 regulates injury responses in the kidney in the setting of ischemia reperfusion injury.
Aim 1 asks how AIM2 regulates the NLRP3 inflammasome (a well-described trigger of renal IR injury) in RTE
cells (the cell type most vulnerable to renal IR injury), by defining the mechanisms by which AIM2 regulates
NLRP3 inflammasome priming, assembly; and subsequent release of IL1b/IL18 and pyroptosis.
Aim 2 focuses on understanding the relative role of AIM2 in the kidney in vivo. The experiments in this aim will
broadly assess kidney-specific mediators of injury vs. inflammatory mediators of injury using a kidney
transplant model that allows injury responses of the aim2-/- kidney to be studied in a WT host, and WT kidney
injury to be studied in the aim2-/- host.
Health Relatedness of Project: If the aims of this proposal are met we will learn how AIM2 participates as a
negative regulator of injury responses in the kidney. This knowledge is crucial for the development of rational
targeted therapies for prevention or amelioration of renal injury in clinical situations where hypoxia is
anticipated. Focusing on the earliest events of ischemic kidney injury holds the greatest promise for effective
therapeutic strategies.

## Key facts

- **NIH application ID:** 10170263
- **Project number:** 5R21AI154471-02
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Dianne B Mckay
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $221,875
- **Award type:** 5
- **Project period:** 2020-05-22 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10170263

## Citation

> US National Institutes of Health, RePORTER application 10170263, AIM2 as a negative regulator of renal ischemia/reperfusion injury (5R21AI154471-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10170263. Licensed CC0.

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