# Revealing the mechanisms of increased intestinal epithelial cell barrier permeability in peanut allergy

> **NIH NIH K08** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $202,314

## Abstract

PROJECT SUMMARY/ABSTRACT
This proposal represents a five-year research career development program focused on understanding intestinal
epithelial cell (IEC) barrier dysfunction in peanut allergy and on providing a strong foundation for the applicant,
Dr. Erin Steinbach, to build an independent basic and translational research career. The candidate is currently
a tenure track Assistant Professor of Medicine at the University of North Carolina (UNC) School of Medicine in
the Division of Rheumatology, Allergy, and Immunology. She is a member of the Thurston Arthritis Research
Center and Center for Gastrointestinal Biology and Disease. The proposal builds on the candidate’s previous
mucosal immunology research and clinical allergy training by integrating five new realms of expertise
represented by her mentor team of Drs. Shehzad Sheikh and Wesley Burks and her advisors’ expertise in IEC
biology, gene regulation, metabolomics and integration of large datasets, and prospective human studies. This
work will add to the existing knowledge of a diverse group of diseases associated with increased IEC permeability
and will foster the development of novel therapies targeting the intestines for severe allergic reactions. Through
formal coursework, seminars, and guidance from her team, the candidate will develop the skills needed to run a
successful research program. She will develop a unique skillset for competing successfully for R01-level grants
that will support her transition to an independent physician scientist career.
Peanut is the most common cause of death from food-related anaphylaxis. Severity of a food allergic reaction is
partly determined by IEC barrier dysfunction, suggesting that peanut is adept at affecting the IEC barrier. No one
has worked out how or why people with peanut allergy have increased IEC barrier permeability. Our preliminary
data show that barrier permeability after the development of peanut allergy persists even in isolated, cultured
IECs. We will use a novel Collaborative Cross mouse model (CC027 strain) and primary human 2D “enteroids”
(primary human-derived IEC monolayers) to broaden the understanding of increased IEC permeability in peanut
allergy. CC027 mice develop peanut allergy through the oral route without adjuvant, which is normally needed
in animal models to establish peanut allergy. The CC027 peanut-allergic mouse develops increased intestinal
permeability. Peanut-allergic CC027 mouse-derived IECs have altered proliferation and cholesterol metabolism,
gut dysbiosis, and produce very high levels of Angiopoietin-like 4 (ANGPTL4). Serum ANGPTL4 levels are higher
in peanut-allergic, compared to non-allergic, pediatric patients. Alterations in the gut microbiota are present in
food allergy and affect the IEC barrier, but its effects in IEC barrier function in peanut allergy remain elusive. We
hypothesize that in established peanut allergy, more local IEC ANGPTL4 production and an altered microbial
metabolome disrupts inte...

## Key facts

- **NIH application ID:** 10887064
- **Project number:** 1K08AI175655-01A1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Erin C. Steinbach
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $202,314
- **Award type:** 1
- **Project period:** 2024-08-15 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10887064

## Citation

> US National Institutes of Health, RePORTER application 10887064, Revealing the mechanisms of increased intestinal epithelial cell barrier permeability in peanut allergy (1K08AI175655-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10887064. Licensed CC0.

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