# Mechanisms of interactions between von Willebrand factor and its binding partners

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2024 · $703,329

## Abstract

SUMMARY
 Von Willebrand factor (VWF) has two major roles in blood. One is to facilitate platelet adhesion and
aggregation, in which a critical step is to activate the VWF A1 domain to bind with platelet protein GPIbα under
flow. The other is to protect coagulation factor VIII (FVIII) from degradation, which is important for fibrin clot
formation. Mutations in VWF interfering with these binding interactions can cause thrombosis or von Willebrand
disease. The goal of this project is to determine molecular mechanisms governing the interactions between VWF
and its binding partners GPIbα and FVIII.
 Several questions regarding VWF interactions with GPIbα and FVIII persist. There has not been a
consistent model for how VWF A1 domain is activated to bind with GPIbα. It still remains unclear which and how
conformational changes actually happen during A1 activation. To date, the interaction between VWF multimer
and FVIII has been studied primarily using bulk VWF preparations. How FVIII binds to individual VWF multimers
is unknown. In intravenous infusion treatment for bleeding disorders, more free FVIII in the infusion is linked to
higher risk of FVIII immunogenicity, but the mechanisms remain unclear.
 In this project, we will combine single molecule biophysics and super resolution imaging methods to study
the following aims. (1) Understand flow-induced activation of VWF A1 binding with GPIbα. (2) Dissect the VWF-
FVIII binding mode and its role in protecting FVIII in blood. This study will provide direct evidence for the
mechanisms of how VWF binds with GPIbα and FVIII, and provide new insights into therapeutic development to
treat thrombotic or bleeding disorders.

## Key facts

- **NIH application ID:** 10911783
- **Project number:** 5R01HL167688-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Hongxia Fu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $703,329
- **Award type:** 5
- **Project period:** 2023-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10911783

## Citation

> US National Institutes of Health, RePORTER application 10911783, Mechanisms of interactions between von Willebrand factor and its binding partners (5R01HL167688-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10911783. Licensed CC0.

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