# Molecular Mechanisms of Uric Acid Homeostasis

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $347,625

## Abstract

Uric acid (UA) is a terminal metabolite of the purine metabolic pathway in humans. Excess UA, the clinical
disorder hyperuricemia, affects 43 million Americans causing gout and increasing risk for hypertension, stroke,
metabolic syndrome, and chronic kidney disease. A genetic and physiological approach led to our identification
of the multidrug transporter ABCG2 as a high capacity UA efflux transporter and that common ABCG2 variants
make the largest genetic contribution to increased UA levels and gout risk. Although the genetic role of
ABCG2 in hyperuricemia and gout risk is now well established, we know little of the physiological role of
ABCG2 as a renal UA transporter. The process of UA homeostasis is by necessity a dynamic process as diet
and metabolism produce highly variable UA loads. Thus, the overarching goal of this proposal is to develop a
mechanistic explanation of how ABCG2 mediated renal UA excretion is physiologically regulated, and how
dysfunction of the process leads to hyperuricemia and human disease. The AIMs of our proposal will address
the following three questions: 1) Is ABCG2 physiologically regulated in vivo and a critical component of UA
homeostasis? 2) What role does phosphorylation play in regulating ABCG2 and renal UA excretion? and 3)
How does the common ABCG2 gout mutation Q141K alter ABCG2 regulation and the physiology of renal UA
excretion? This work will provide a new understanding of the molecular mechanisms of urate homeostasis and
illuminate both the consequences of dysregulated hyperuricemia on human health, and novel therapeutic
targets for treatment.

## Key facts

- **NIH application ID:** 9925221
- **Project number:** 5R01DK114091-04
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** OWEN M WOODWARD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $347,625
- **Award type:** 5
- **Project period:** 2017-08-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9925221

## Citation

> US National Institutes of Health, RePORTER application 9925221, Molecular Mechanisms of Uric Acid Homeostasis (5R01DK114091-04). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/9925221. Licensed CC0.

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