# Uncovering Mechanisms of Risk-Variant APOL1-modulated Inflammatory Signaling in Macrophages

> **NIH NIH F31** · NORTHWESTERN UNIVERSITY · 2024 · $44,187

## Abstract

Project Summary
Chronic kidney disease (CKD), the graduate loss of kidney function, is an incurable condition which affects more
than 37 million individuals in the United States and is costly to manage. In particular, Black Americans face a
higher risk to develop CKD and progress to end stage kidney disease (ESKD) even after accounting for clinical
and socioeconomic factors. Recently, variants in the gene encoding for Apolipoprotein L1 (APOL1) have been
identified as risk factors for focal segmental glomerulosclerosis (FSGS) and HIV-associated nephropathy
(HIVAN) in individuals with recent African ancestry. However, the cell-specific mechanisms that cause disease
are not well understood. In this study we propose to better understand the effect of risk variant APOL1 on
macrophage function and inflammation. Specifically, we hypothesize that risk variant APOL1 hinders the
macrophage's ability to polarize toward an anti-inflammatory phenotype and thus prolongs inflammation in the
kidney after injury. Because APOL1 is found only in humans and new-world primates, we will use induced
pluripotent stem cell (iPSC)-derived macrophages to more accurately model native genomic regulation of
APOL1. To recapitulate the kidney microenvironment and its effects on macrophage activation, we will induce
inflammatory kidney injury in transgenic mice expressing the APOL1 variants. In both iPSC-derived
macrophages and transgenic mouse kidney macrophages we will observe the effects of risk variant APOL1 on
inflammatory signaling, metabolic activity, and mitochondria-mediated autophagy. We will also evaluate the
effect of risk variant APOL1 on anti-inflammatory polarization in macrophages. The goal of this study is to unveil
the mechanisms in risk variant APOL1 macrophages which contribute to kidney disease progression.

## Key facts

- **NIH application ID:** 10820518
- **Project number:** 1F31DK131884-01A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Esther Liu
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $44,187
- **Award type:** 1
- **Project period:** 2024-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10820518

## Citation

> US National Institutes of Health, RePORTER application 10820518, Uncovering Mechanisms of Risk-Variant APOL1-modulated Inflammatory Signaling in Macrophages (1F31DK131884-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10820518. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*