# Role of lung WWOX deficiency in vascular leak during lung injury

> **NIH NIH K08** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $174,172

## Abstract

Project Summary/Abstract
Acute respiratory distress syndrome (ARDS) is a critical illness that afflicts an estimated
200,000 patients/year in the United States alone, kills approximately 75,000, and is seriously
debilitating for many survivors. Specific ARDS therapies do not currently exist, and efforts to
reduce its burden have been limited by an incomplete characterization of the diverse molecular
mechanisms underlying its pathogenesis. The cardinal, morbidity-producing feature of ARDS is
non-cardiogenic pulmonary edema resulting from pulmonary vascular barrier disruption with
consequent alveolar flooding, and respiratory failure. The conceptual underpinning for these
events consists of cytoskeletal contraction of pulmonary endothelial cells (ECs) leading to the
formation of paracellular gaps. Novel strategies which reduce the vascular permeability and
lung edema of ARDS are desperately needed. The objective of this proposal is to determine the
contribution of the tumor suppressor WWOX to the pathobiological processes associated with
ARDS. WWOX resides at the second most active common chromosomal fragile site in the
human genome, making it highly susceptible to genotoxic stress such as that which occurs
during cigarette smoke and other toxic respiratory exposures. Data detailed in this application
suggests that 1) loss of WWOX occurs in the lung during cigarette smoke exposure, and this
event may at least partly explain an increased susceptibility for severe ARDS in smokers versus
nonsmokers observed in currently emerging evidence from epidemiologic studies, and 2)
WWOX exerts potent EC barrier-protective effects during both in vivo and in vitro
lipopolysaccharide (LPS)-induced ARDS. This project aims to 1) determine the significance of
EC WWOX expression in murine ARDS, 2) define the molecular mechanisms by which WWOX
promotes EC barrier protection and 3)Establish the conceptual basis for WWOX-based therapy
in cigarette-smoke primed, sepsis-induced ARDS.

## Key facts

- **NIH application ID:** 9983155
- **Project number:** 5K08HL140222-03
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Sunit Singla
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $174,172
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983155

## Citation

> US National Institutes of Health, RePORTER application 9983155, Role of lung WWOX deficiency in vascular leak during lung injury (5K08HL140222-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9983155. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*