# Polarity proteins and intestinal mucosal responses to inflammation and injury

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $482,628

## Abstract

Abstract
The gastrointestinal epithelium plays a central role in maintaining barrier function while coordinating mucosal
homeostasis and immunity. An important negative consequence of excessive inflammation, ischemia, certain
infections, and other clinical conditions is mucosal epithelial injury and wounding that serves to compromise
the epithelial barrier which is tightly regulated by intercellular junctions that include the tight junction (TJ) and
adherens junction (AJ), collectively referred to as the Apical Junctional Complex (AJC). Proteins involved in
regulating epithelial polarity such as the Crumbs family of proteins, influence organization and function of the
AJC and regulate epithelial homeostasis and differentiation. Since most of studies on polarity proteins have
been performed in model organisms and transformed cell lines, current knowledge of the molecular basis by
which polarity proteins orchestrate intestinal epithelial barrier function and wound repair in vivo in mammals
remains limited. The overall goal of this proposal is to identify how the polarity protein Crumbs 3 (CRB3)
controls epithelial homeostasis, namely barrier function and wound repair in vivo using CRB3 transgenic mice
and natural human and murine intestinal epithelium. Our overarching hypothesis is that CRB3 functions as a
master regulator of intestinal epithelial barrier function and wound repair by controlling assembly of different
adhesion-cytoskeletal modules at the plasma membrane. Knowledge gained from these studies in the short
term will provide important new insights on basic mechanisms by which polarity proteins regulate the intestinal
epithelial barrier and repair. In the long term, these studies will likely provide ideas for development of new
therapeutic strategies aimed at strengthening the epithelial barrier and in promoting intestinal mucosal wound
repair.

## Key facts

- **NIH application ID:** 10786050
- **Project number:** 5R01DK129214-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** ASMA NUSRAT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $482,628
- **Award type:** 5
- **Project period:** 2022-04-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10786050

## Citation

> US National Institutes of Health, RePORTER application 10786050, Polarity proteins and intestinal mucosal responses to inflammation and injury (5R01DK129214-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10786050. Licensed CC0.

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