# Identify cell surface protein ligand candidates for understudied adhesion GPCRs using a sensitive cell-based approach

> **NIH NIH R03** · NEMOURS CHILDREN'S HOSPITAL, DELAWARE · 2022 · $142,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Adhesion G protein-coupled receptors (aGPCRs) are a group of 33 poorly characterized non-olfactory GPCRs
with distinct features including autocatalytic processing and large extracellular regions. aGPCRs are involved
in a myriad of biological processes and some of them are associated with diseases, especially a wide range of
cancers. The extracellular regions of many of the aGPCRs contain domains that are known to be involved in
protein-protein interactions, suggesting that binding to cell surface protein ligands may play an important role in
their mechanisms of action. The majority of aGPCRs, however, are orphan receptors without known ligands.
Identification of ligands for these aGPCRs should help understand their physiological functions and roles in
cancer development. A major challenge for identifying ligands involved in ligand-receptor interactions at the
cell-cell interface is that they tend to bind their receptors very weakly and currently available methods do not
have enough sensitivity. To overcome this, we propose to employ a novel and highly sensitive cell-based
approach to identify protein ligands for 17 understudied orphan aGPCRs. The feasibility of the approach has
been tested using model ligands and receptors that are known bind to each other with low affinities. We will
use the cell-based approach to screen a collection of transmembrane proteins to identify ligand candidates for
the aGPCRs. Ligand candidates identified in this study will pave the way for more in-depth characterization of
their bindings to respective aGPCRs and the functional consequences of the bindings in future studies.

## Key facts

- **NIH application ID:** 10452320
- **Project number:** 1R03TR004206-01
- **Recipient organization:** NEMOURS CHILDREN'S HOSPITAL, DELAWARE
- **Principal Investigator:** Zhengyu Ma
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $142,000
- **Award type:** 1
- **Project period:** 2022-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10452320

## Citation

> US National Institutes of Health, RePORTER application 10452320, Identify cell surface protein ligand candidates for understudied adhesion GPCRs using a sensitive cell-based approach (1R03TR004206-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10452320. Licensed CC0.

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