# BLRD Research Career Scientist Award Application

> **NIH VA IK6** · JAMES A. HALEY VA MEDICAL CENTER · 2020 · —

## Abstract

The overall objective of this application is to expand my current project towards a new phase to
further investigate the molecular control of cell specific mechanisms that contribute to the diseases
that are commonly in American Veterans. The future research focuses on the role of focal adhesion
kinase (FAK) in the regulation of gut barrier injury during trauma. Additional efforts will be devoted in
collaboration with VA surgeons to examining molecular mechanisms of endothelial barrier
dysfunction and MMP dysregulation that lead to the failure of vascular remodeling in VA patients.
Trauma-induced inflammation and multiple organ failure are major causes of mortality and
morbidity in American soldiers and veterans. Gut barrier dysfunction plays a critical role in the
development of posttraumatic complications by providing the major site for plasma leakage and
bacterial translocation. The intestinal epithelial barrier damage in burns, a major form of trauma, has
not been well characterized clinically. In addition, its cellular and molecular mechanisms remain
incompletely understood. The major goal of application is to elucidate the cell-specific mechanisms
of leaky guts during thermal injury. We hypothesize that thermal injury induced inflammation in gut
tissue activates Src and FAK activity in intestinal epithelium, stimulate focal remodeling and ZO1
mediated junction disassociation therefore impairing gut epithelial barrier integrity. The specific goals
developed in this study are: 1) to analyze the molecular mechanism of FAK mediated gut epithelial
barrier dysfunction, and 2) to evaluate the functional role of FAK activation and therapeutic potential
of FAK inhibition in gut barrier dysfunction during thermal injury. 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 pathway in the regulation of
tight and adherens junctions. Information gleaned from the research work will not only contribute to
the advancement of gastrointestinal pathobiology, but also has clinical implications in the
development of effective therapies or surgical interventions against gut barrier injury in the VA
patients with trauma and inflammatory bowel diseases.

## Key facts

- **NIH application ID:** 9899092
- **Project number:** 5IK6BX004210-03
- **Recipient organization:** JAMES A. HALEY VA MEDICAL CENTER
- **Principal Investigator:** MACK H WU
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899092

## Citation

> US National Institutes of Health, RePORTER application 9899092, BLRD Research Career Scientist Award Application (5IK6BX004210-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9899092. Licensed CC0.

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