# Thiol isomerases in neutrophil recruitment and thromboinflammatory disease

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $19,381

## Abstract

Project Summary
Neutrophil recruitment to sites of inflammation is a multi-step process mediated by the interactions between
several receptors and ligands. Although the major receptors and ligands mediating neutrophil-endothelial cell
interactions have been identified, it remains poorly understood how receptor-ligand interactions are regulated
under inflammatory conditions. This project will provide novel fundamental knowledge of how neutrophil surface-
localized ERO1α-thiol isomerase complexes target allosteric disulfide bonds in different surface receptors and
promote the ligand-binding function under inflammatory conditions. Our preliminary data demonstrated that
neutrophil surface-bound ERp57 and PDI cooperatively and distinctly regulate the process of neutrophil
recruitment and extracellular ERO1α coordinates this regulatory mechanism. Using biochemical, cellular, and in
vivo studies with novel blocking antibodies, peptides and mouse models, we will test the hypothesis that two
structurally-similar thiol isomerases, ERp57 and PDI and their oxidase ERO1α facilitate modification of allosteric
disulfide bonds in different surface molecules and enhance neutrophil adhesive function, contributing to tissue
damage under thromboinflammatory conditions. In Aim 1, we will determine how PDI and ERp57 distinctly
regulate the adhesive function of different neutrophil receptors. Also, we will test whether extracellular ERO1α
controls the activity of those thiol isomerases. In Aim 2, we will test how inflammatory environments influence
the function of extracellular PDI, ERp57 and ERO1α. In Aim 3, using in vivo live imaging techniques, we will
study the pathological roles of extracellular PDI, ERp57 and ERO1α in intravascular cell-cell interactions and
tissue damage in thromboinflammation. Our studies will provide insights into novel molecular and cellular
mechanisms of neutrophil-endothelial cell interactions, which can be used to design new strategies for the
treatment of thromboinflammatory disease.

## Key facts

- **NIH application ID:** 9862840
- **Project number:** 2R01HL130028-05
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Jaehyung Cho
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $19,381
- **Award type:** 2
- **Project period:** 2016-09-01 → 2020-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9862840

## Citation

> US National Institutes of Health, RePORTER application 9862840, Thiol isomerases in neutrophil recruitment and thromboinflammatory disease (2R01HL130028-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9862840. Licensed CC0.

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