# Enteroendocrine cell reprogramming during intestinal injury

> **NIH VA IK2** · ST. LOUIS VA MEDICAL CENTER · 2021 · —

## Abstract

RESEARCH STRATEGY: The primary research objective of this proposal is to address how subtypes of
enteroendocrine cells change their activity (secretion) or state of differentiation in response to injury signals. A
better understanding of intestinal injury repair is critical to VA health priorities; the prevalence of inflammatory
bowel disease (IBD) has more than doubled among VA patients since 1998 and at least half of patients won’t
experience full mucosal healing with existing therapies. Hormones produced in intestinal enteroendocrine cells
(EEC) are altered in patients with IBD and can promote epithelial healing, but there is little understanding of
how EEC secretion is regulated during injury. The study of EECs has been limited because they are rare,
heterogenous, and not amenable to long-term primary culture with existing methods. To address this gap, we
have developed a new experimental system to culture EECs from primary colon samples in long-term
monolayers that supports all known EEC subtypes. We have discovered that subtypes of EEC are dynamically
altered with a simple experimental injury in vitro. The altered EECs increase the expression of factors that
promote intestinal healing. The goal of this proposal is to determine the cellular and transcriptional basis of
how subtypes of EEC respond to intestinal injury through altered activity or differentiation. Our Aims are to (1)
test the hypothesis that subtypes of EECs are adaptively reprogrammed by injury induced endoplasmic
reticulum (ER) stress, (2) test the hypothesis that microenvironmental injury signals reprogram EECs to
increase hormone secretion, and (3) define the transcriptional mechanisms of EEC reprogramming during
injury at single-cell resolution. The expected outcome of this work is to establish the new paradigm that
EECs undergo adaptive reprogramming during injury which will serve as the foundation for future independent
grant proposals. Additionally, we expect to discover novel secreted factors or altered states of differentiation in
EEC that would lead to new potential treatments for veterans suffering from intestinal or metabolic disorders.
CANDIDATE/ENVIRONMENT: Dr. Brian Muegge is a senior fellow in the Division of Endocrinology at
Washington University in St. Louis and the St. Louis VA Medical Center. He completed his M.D., Ph.D. training
at Washington University where he performed graduate studies in Dr. Jeffrey Gordon’s laboratory. Dr. Muegge
completed his residency in internal medicine at UCSF. He is conducting his fellowship research in the lab of his
primary mentor Dr. Thaddeus Stappenbeck and co-mentor Dr. Carlos Bernal-Mizrachi at Washington
University. Dr. Muegge has gained experience in intestinal stem cell culture and computational analysis of
transcriptional data. He has developed a novel culture system that allows him to model EEC development and
injury using primary cells. He now seeks to expand his expertise in new areas including lineage tracing, cell...

## Key facts

- **NIH application ID:** 10087791
- **Project number:** 5IK2BX004909-02
- **Recipient organization:** ST. LOUIS VA MEDICAL CENTER
- **Principal Investigator:** Brian David Muegge
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10087791

## Citation

> US National Institutes of Health, RePORTER application 10087791, Enteroendocrine cell reprogramming during intestinal injury (5IK2BX004909-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10087791. Licensed CC0.

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