# Molecular Mechanisms of Histone-Induced Endotheliopathy in Trauma

> **NIH NIH R35** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2024 · $390,000

## Abstract

Injury and trauma are common conditions that encompass a considerable burden of illness and account for a
major component of health care costs. Endothelial cells (ECs) are the nexus between the blood and the body,
and disruption of endothelial function in trauma leads to a syndrome of endothelipathy characterized by impaired
microvascular blood flow, barrier integrity and coagulation. Our lack of understanding of how ECs translate the
signals of trauma into changes in vasodilatory, barrier and coagulation functions represents a significant void—
but also an opportunity for clinical intervention. The central theme of my lab is to understand endotheliopathy in
trauma and inflammation, so that we can improve outcomes. This research program will deliver a molecular
model of the mechanisms by which histones cause both immediate and sustained effects on vascular
endothelium that explain oscillating clotting responses seen in trauma patients. This project will also test novel
strategies to protect and/or rescue endothelial dysfunction after trauma. The proposed research is expected to
significantly advance the continuum of research needed to improve diagnosis and management of acute
endotheliopathy in trauma. Moreover, it has the potential to radically change our view of endothelial biology. This
research will provide an enduring and sustained impact on understanding the role of the endothelium in health
and disease.

## Key facts

- **NIH application ID:** 10748375
- **Project number:** 5R35GM144099-03
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** Kalev Freeman
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $390,000
- **Award type:** 5
- **Project period:** 2022-01-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10748375

## Citation

> US National Institutes of Health, RePORTER application 10748375, Molecular Mechanisms of Histone-Induced Endotheliopathy in Trauma (5R35GM144099-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10748375. Licensed CC0.

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