# “Protection from MRSA lethality by inhibiting LXRα phosphorylation”

> **NIH NIH R21** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $211,875

## Abstract

PROJECT SUMMARY
This proposal aims to determine whether LXRα phosphorylation at serine 196 (S196) is a possible target for
therapeutic intervention in MRSA. Our previous published studies demonstrated in cultured cells and mouse
models of cardiometabolic diseases that the non-phosphorylated form of LXRα S196A reprograms the LXR-
modulated transcriptome and produces a more robust anti-inflammatory response. We hypothesize that reducing
LXRα phosphorylation in myeloid and endothelial cells would reduce MRSA pathology via resistance to MRSA
toxin-mediated killing via enhanced exosome release.
To test this, we will develop a mouse model that harbors either myeloid or endothelial cell-specific LXRα S196A
knock-in mice and compare the mortality and exosome abundance in the blood upon MRSA infection to that of WT
LXRα mice and global LXRα S196A mice. We will also generate primary macrophages and endothelial cells from
wild-type and LXRα S196A mice and measure effects on gene expression upon infection with MRSA to reveal
genes and pathways modulated by LXRα S196 phosphorylation that can be manipulated for preventive and
therapeutic purposes. We will also test whether pharmacological interventions that promote the non-
phosphorylated form of the wild-type LXRα can protect wild-type mice and human PBMCs from lethal MRSA
infection. Successful completion of the aims will determine whether LXRα phosphorylation represents a tractable
target for treating MRSA due to its ability to reduce inflammatory gene expression.

## Key facts

- **NIH application ID:** 10791916
- **Project number:** 5R21AI176657-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Michael J. Garabedian
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $211,875
- **Award type:** 5
- **Project period:** 2023-02-17 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10791916

## Citation

> US National Institutes of Health, RePORTER application 10791916, “Protection from MRSA lethality by inhibiting LXRα phosphorylation” (5R21AI176657-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10791916. Licensed CC0.

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