# Role of sumoylation in vascular endothelial barrier dysfunction in sepsis

> **NIH NIH R21** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $239,850

## Abstract

Vascular leakage resulting from endothelial barrier dysfunction is a common mechanism of multiple organ
failure that mainly contributes to the morbidity and mortality in patients with sepsis. Identifying novel
therapeutic targets that can effectively maintain vascular integrity is crucial to treat septic patients. The
intercellular adhesion protein vascular endothelial (VE)-cadherin is the most important molecule in forming the
adherens junctions, as well as regulating the endothelial barrier function. VE–cadherin expression in cell-cell
junctions is stabilized by binding to p120-catenin (p120). Our preliminary data indicate that p120 sumoylation
plays a crucial role in regulating the interaction of p120 and VE-cadherin and endothelial barrier function in
sepsis. In this proposal, we will test the hypothesis that p120 sumoylation is the critical determinant of p120-
VE-cadherin dissociation, endothelial barrier dysfunction and vascular endothelial hyperpermeability during
sepsis. Two Specific Aims are proposed as follows: Aim 1. To elucidate the molecular mechanisms by which
p120 sumoylation regulates endothelial barrier function during sepsis. Aim 2: To evaluate the role of p120
sumoylation in vascular leakage and survival during polymicrobial sepsis and test the therapeutic potential of
targeting p120 sumoylation for treating septic injury. These comprehensive studies will utilize genetic, imaging,
pharmacological and physiological approaches to investigate molecular mechanisms of p120 sumoylation in
the regulation of endothelial barrier integrity and assess the therapeutic potential of inhibition of p120
sumoylation in improving lung edema and survival during sepsis.

## Key facts

- **NIH application ID:** 9988095
- **Project number:** 1R21AI152249-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Guochang Hu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $239,850
- **Award type:** 1
- **Project period:** 2020-03-04 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988095

## Citation

> US National Institutes of Health, RePORTER application 9988095, Role of sumoylation in vascular endothelial barrier dysfunction in sepsis (1R21AI152249-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9988095. Licensed CC0.

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