# Ero1α in platelet activity and thrombosis

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $459,057

## Abstract

Project Summary
Despite advances in our understanding of the mechanisms mediating platelet thrombus formation, current
antiplatelet drugs increase the risk of major bleeding. In an effort to identify novel therapeutic targets, we and
others showed that intravascular protein disulfide isomerase (PDI) is crucial for full activation of αIIbβ3 integrin
and platelet accumulation in arterial thrombosis, providing insights into a new antithrombotic agent. However,
blocking the oxidoreductase activity of intravascular PDI prolongs tail bleeding times in mice. Our preliminary
data have demonstrated that endoplasmic reticulum (ER) oxidoreductin 1α (Ero1α), a key oxidase of PDI in the
ER, is released from activated platelets and that inhibition or deletion of platelet Ero1α alters the activity of
platelet surface-bound PDI and impairs platelet aggregatory function. Furthermore, we have found that global
deletion of Ero1α reduces the size of platelet thrombus formation without affecting initial platelet adhesion and
tail bleeding times following vascular injury. Using biochemical, cellular and in vivo animal studies with novel
pharmacological inhibitors and Ero1α conditional knockout and global knockout mice developed by our lab, we
will test the hypothesis that platelet-released Ero1α regulates the function of PDI and αIIbβ3 integrin on the cell
surface and contributes to the propagation step of platelet thrombus formation without affecting hemostasis
following vascular injury. In Aim 1, we will identify the molecular mechanism by which extracellular Ero1α
promotes platelet aggregation. In Aim 2, we will test whether arterial thrombotic conditions alter the function of
extracellular Ero1α. In Aim 3, we will determine the pathophysiological role of intravascular and platelet-derived
Ero1α in platelet adhesion and accumulation and vessel occlusion under thrombotic conditions. The proposed
studies will identify a central regulatory mechanism of platelet thrombus formation and lead to the discovery of
novel therapeutic strategies for the safe and effective treatment of thrombotic disease.

## Key facts

- **NIH application ID:** 9884277
- **Project number:** 1R01HL146559-01A1
- **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:** $459,057
- **Award type:** 1
- **Project period:** 2020-02-01 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9884277

## Citation

> US National Institutes of Health, RePORTER application 9884277, Ero1α in platelet activity and thrombosis (1R01HL146559-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9884277. Licensed CC0.

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