# Structure and pharmacology of GPR32 in the resolution of inflammation

> **NIH NIH R03** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $156,500

## Abstract

Project Summary
Inflammation is a complex process with many lipid mediators involved. A large number of these mediators are
eicosanoid lipids that promote either pro-inflammatory or pro-resolving effects through action on G protein-
coupled receptors (GPCRs). These eicosanoid lipids share a high chemical similarity. However, they target
different GPCRs and elicit distinct roles in inflammation, potentially by inducing different signaling pathways.
The mechanism underlying the signaling of eicosanoid lipids is largely unknown. Our group studies an
important family of eicosanoid GPCRs that comprises receptors for both pro-inflammatory eicosanoid lipids
such as prostaglandin D2 (PGD2) and specialized pro-resolving lipid mediators (SPMs) such as lipoxin A4
(LXA4) and resolvin D1 (RvD1), aiming to understand the molecular mechanisms for ligand recognition and
receptor signaling. We published the first structures of antagonist-bound DP2 as the receptor for PGD2.
Recently, we obtained a crystal structure of lipid-bound DP2 and a cryo-EM structure of another receptor in this
family, FPR2/ALX, as the receptor for LXA4. Built on such progress, we propose to further study the structure
and pharmacology of GPR32 as the receptor for resolvin D1. We aim to gain a comprehensive structural
understanding of how pro-resolving agents act on and signal through GPR32 and use the structural information
to develop novel GPR32 ligands as useful research tools and potential drug candidates. In the proposed
initiatives, we will establish experimental systems to obtain samples of GPR32 and GPR32 signaling complex
for structural characterization by cryo-EM. We will also obtain a structural model of GPR32 based on our
structure of lipid-bound DP2 and use it to predict new GPR32 ligands. The results will provide a solid
foundation for our future research efforts in the structural elucidation of GPR32 signaling and structure-based
development of new GPR32 ligands as novel pro-resolving agents.

## Key facts

- **NIH application ID:** 10217380
- **Project number:** 1R03TR003306-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** CHENG ZHANG
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $156,500
- **Award type:** 1
- **Project period:** 2021-04-15 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217380

## Citation

> US National Institutes of Health, RePORTER application 10217380, Structure and pharmacology of GPR32 in the resolution of inflammation (1R03TR003306-01A1). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10217380. Licensed CC0.

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