# RHO-ASSOCIATED KINASE-DEPENDENT CYTOSKELETAL AND TIGHT JUNCTION DYSREGULATION IN NECROTIZING ENTEROCOLITIS

> **NIH NIH R03** · LURIE CHILDREN'S HOSPITAL OF CHICAGO · 2020 · $7,650

## Abstract

PROJECT SUMMARY/ ABSTRACT:
Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of newborns, and affects 7% of
patients admitted to a neonatal intensive care unit. Despite years of research there is a gap in the understanding
of the underlying pathophysiology of disease, and a lack of novel therapeutic approaches. Rho kinases (ROCK)
are serine/ threonine kinases and are involved in multiple cellular processes including regulating tight junction
function, actin cytoskeleton contraction, inflammatory cytokines and cell death. We and others, have previously
demonstrated the relevance of these pathways to the pathophysiology of NEC. The objectives of this R03
proposal are to define mechanism(s) of ROCK activation, identify molecular pathways targeted by ROCK during
experimental NEC and to determine the mechanisms by which ROCK inhibition limits NEC progression. The
central hypothesis is that oxidative stress and LPS induce ROCK activation, resulting in cytoskeletal contraction
and tight junction degradation that enhances mucosal and systemic inflammation and epithelial apoptosis. If this
hypothesis is correct then ROCK inhibition will be protective against these effects and NEC. To test this
hypothesis, we will examine the effects of signaling through ROCK pathway on tight junction proteins, epithelial
permeability, inflammation and apoptosis during experimental NEC. The objective of this application is to define
the ROCK-mediated molecular interactions that direct epithelial function during NEC. These studies will have
great power since they will be performed in vitro, in enteroids, and in vivo models of NEC as well as in human
intestinal samples from infants with and without NEC. We will determine whether inhibition of the ROCK pathway
(by pharmacological and genetic approaches) can stabilize tight junctions and minimize inflammation, decrease
cell death, and influence the outcomes and survival in experimental NEC. These findings will build upon my
current studies, and have a significant positive impact on human health by providing a new understanding of the
mechanisms governing epithelial intestinal barrier function during NEC.

## Key facts

- **NIH application ID:** 9851394
- **Project number:** 5R03DK117216-03
- **Recipient organization:** LURIE CHILDREN'S HOSPITAL OF CHICAGO
- **Principal Investigator:** Catherine Jane Hunter
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $7,650
- **Award type:** 5
- **Project period:** 2019-02-01 → 2020-01-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851394

## Citation

> US National Institutes of Health, RePORTER application 9851394, RHO-ASSOCIATED KINASE-DEPENDENT CYTOSKELETAL AND TIGHT JUNCTION DYSREGULATION IN NECROTIZING ENTEROCOLITIS (5R03DK117216-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9851394. Licensed CC0.

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