# Zimmerman Program on the Biology of VWD

> **NIH NIH P01** · VERSITI BLOOD HEALTH, INC. · 2021 · $2,638,519

## Abstract

PROJECT SUMMARY: OVERALL
This Program Project Grant on remaining critical issues concerning the molecular and biologic control of von
Willebrand factor in von Willebrand disease. This PPG is comprised of 4 projects and 3 cores that are all
focused on von Willebrand disease and mechanisms causing its dysfunction, increased clearance or increased
synthesis, and the role carbohydrate modification play in VWF biology. While this represents a new PPG
application, this PPG makes use of the samples and biodata from the pre-existing PPG on historically
diagnosed subjects and an R01 grant on new VWD subjects recruited prospectively. Project 1 includes aims to
define longitudinal changes in VWF concentration and changes in semiquantitative bleeding assessment
during follow-up intervals, the fidelity of the diagnosis of type 2 VWD, the frequency of antibodies to VWF in
type 3 VWD, and the development of animal models of VWD and VWD variants. Subjects with low von
Willebrand factor (LVWF), and type 1 or 3 VWD with no sequence variants will be studied in Core B with full
genome sequencing. Abnormalities identified will be sought in their family members through Project 1 and the
mechanism studied by projects 1, 2, 3, or 4 based on candidate pathway. Project 2 will define the role of
carbohydrate modification of VWF through determination of N- and O-glycan profiles, study the glycan
differences in plasma, endothelial and platelet VWF, and racial differences using MS-glycomic and
glycoproteomic approaches. Model systems will be set up in mice to mirror the changes found in human
mechanisms. Project 3 will examine the upstream regulatory control as a mechanism causing VWD. The cell
biology of VWF will be studied using BOECs obtained from patients with VWD and used to examine the role of
promoters and enhancers. Genetically engineered mice will study the mechanisms by which clearance
receptors alter VWF concentration. Project 4 will study the transcription regulation of VWF and the inhibition
with microRNAs. This project will also examine the role of epigenetics in modulating plasma VWF and the
effect of chronic inflammation on these mechanisms. There are three cores to support this PPG. Core A is the
administrative core that will facilitate exchange of information, data, and patient samples and biodata. It will
also oversee the 10 Primary Clinical Centers that will be following our enrolled subjects. Core B will be doing
whole genome sequencing of subjects with very low or absent VWF that have had normal VWF sequencing.
Core C will develop animal models for each of the projects to further their studies on VWD mechanisms.
Together these studies will comprehensively study unique mechanisms that lead to reduced or abnormal VWF
in VWD.

## Key facts

- **NIH application ID:** 10113367
- **Project number:** 5P01HL144457-03
- **Recipient organization:** VERSITI BLOOD HEALTH, INC.
- **Principal Investigator:** ROBERT R MONTGOMERY
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,638,519
- **Award type:** 5
- **Project period:** 2019-03-15 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10113367

## Citation

> US National Institutes of Health, RePORTER application 10113367, Zimmerman Program on the Biology of VWD (5P01HL144457-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10113367. Licensed CC0.

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