# Molecular Control of Gut Permeability in Trauma

> **NIH VA I01** · JAMES A. HALEY VA MEDICAL CENTER · 2020 · —

## Abstract

Project Summary
Systemic inflammation and multiple organ failure associated with trauma are a major cause of
mortality and morbidity in American soldiers and veterans. Intestinal barrier dysfunction plays
an important role in the development of posttraumatic complications such as sepsis by
providing the major site for diffusion of toxins, allergens and bacterial translocation to the
circulation. Despite the well- recognized importance of gut dysfunction in the pathogenesis of
posttraumatic complications, the intestinal permeability response to severe burns, a major form
of trauma, has not been well characterized, and its cellular and molecular mechanisms have
not been fully understood. The goal of this study is to elucidate the cell-specific mechanisms of
leaky guts during thermal injury. The hypothesis to be tested is that thermal injury induced
inflammation in gut tissue activates focal adhesion kinase (FAK) activity in gut epithelium,
stimulates focal remodeling and epithelial junction disassociation, therefore impairing gut
epithelial barrier integrity. Two specific aims are developed in this proposal to: 1) characterize
functional role of FAK mediated intestinal barrier dysfunction and therapeutic potential of FAK
inhibition during thermal injury, and 2) explore the molecular mechanism of FAK mediated gut
epithelial barrier dysfunction. The study design employs complimentary in vivo, ex vivo, and in
vitro models that incorporate molecular and genetic approaches into physiological experiments
under clinically relevant trauma conditions. The significance of the study lies in its potential to
establish a new molecular mechanism in the regulation of gut epithelial barrier function. The data
derived from this project will enhance our understanding of pathophysiological mechanisms
involved in gut epithelial barrier function. More importantly, it will expand our knowledge of
gastrointestinal pathobiology and contribute to the development of effective therapies and
surgical interventions against gut barrier injury in patients suffered from trauma or inflammatory
diseases.

## Key facts

- **NIH application ID:** 9833435
- **Project number:** 5I01BX000799-10
- **Recipient organization:** JAMES A. HALEY VA MEDICAL CENTER
- **Principal Investigator:** MACK H WU
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2010-04-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9833435

## Citation

> US National Institutes of Health, RePORTER application 9833435, Molecular Control of Gut Permeability in Trauma (5I01BX000799-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9833435. Licensed CC0.

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