# Deciphering the role of Claudin-23 in regulation of the intestinal epithelial barrier

> **NIH NIH F30** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $16,597

## Abstract

PROJECT SUMMARY
 Intestinal epithelial cells (IECs) constitute a selective barrier that regulates nutrient uptake and restricts
antigen access from the lumen to the underlying mucosa. Permeability across the intestinal epithelium is
dynamically regulated by a range of physiologic and pathologic stimuli. Patients with chronic inflammatory bowel
disease (IBD), suffer from debilitating gastrointestinal symptoms that significantly impact their quality of life and
pose a disproportionately large economic burden on the healthcare system. Although genetic susceptibility,
environmental factors, and immune dysregulation are all critical contributors to the multifactorial etiology of IBD,
there is increasing evidence suggesting a central role for intestinal epithelial barrier dysfunction in IBD patients.
Intestinal barrier properties are regulated through dynamic remodeling and maturation of intercellular junctions
along the lateral membrane of IECs. Tight junctions (TJs) are the most apical intercellular junctional complex
and are composed of a highly organized array of transmembrane proteins and cytoplasmic scaffolding proteins
that anchor the complex to the actin cytoskeleton. The claudin (CLDN) family of TJ transmembrane proteins is
comprised of 27 members in humans that control barrier function by regulating the sealing properties of the TJ.
In the colon, CLDNs are differentially expressed to spatially regulate barrier properties. Notably, CLDN
expression is perturbed in IBD and has been linked to barrier compromise. However, the mechanisms by which
IECs differentially express CLDNs to control barrier function and how CLDN dysregulation contributes to
epithelial barrier compromise in IBD remain unclear. In this proposal we present compelling preliminary data
implicating CLDN23, an understudied non-classical claudin family member, as a central orchestrator of CLDN
complex stability and TJ barrier function in IECs. Moreover, we have observed that CLDN23 expression is
dysregulated in IBD. Thus, my proposed studies will employ novel tools to investigate how CLDN23 controls
intestinal epithelial barrier function using complementary in vitro and in vivo techniques. Successful completion
of the proposed studies will expand our knowledge of basic mechanisms that control intestinal epithelial barrier
function in health and disease, and will open new avenues for investigation of therapeutic interventions to restore
barrier properties and ameliorate inflammation in IBD. Importantly, this scientific proposal and training will
position me for a sustained career as a physician-scientist studying the mechanisms of disease of
gastrointestinal inflammatory illnesses.

## Key facts

- **NIH application ID:** 10906295
- **Project number:** 5F30DK132817-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Kristen Michelle Lozada-Soto
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $16,597
- **Award type:** 5
- **Project period:** 2022-09-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906295

## Citation

> US National Institutes of Health, RePORTER application 10906295, Deciphering the role of Claudin-23 in regulation of the intestinal epithelial barrier (5F30DK132817-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10906295. Licensed CC0.

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