# The Msi2 RNA binding protein coordinates epithelial regeneration and the inflammatory response to intestinal mucosal injury

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2020 · $32,947

## Abstract

Project Summary
Breakdown of the intestinal epithelial barrier occurs in many gastrointestinal disorders including inflammatory
bowel disease, pathogen infection, ischemia-reperfusion injury and radiation enteropathy. This barrier
breakdown initiates a regenerative response from the intestinal stem cell compartment and simultaneously elicits
an inflammatory response secondary to epithelial translocation of luminal microbes. Despite the necessity and
proximity of these two processes, little is known about how they are coordinated. Our group has previously
determined that the Msi family of RNA-binding proteins are both necessary and sufficient for activation of a
quiescent pool of facultative intestinal stem cells (qISCs) which mediate intestinal regeneration in response to
injury. We found that Msi2 binds several transcripts governing stem cell cycling and metabolism, as well as a
group of epithelial-specific anti-microbial and immunomodulatory transcripts. Thus, I hypothesize that Msi2
performs dual functions as an enhancer of facultative stem cell activation and a repressor of the immune
response to barrier disruption based on cell type specific RNA binding targets.
In this proposal, I will employ a MSI2-HyperTRIBE fusion protein in the mouse to uncover Msi2 RNA binding
targets that mediate intestinal regeneration (qISC-specific) and the epithelium’s inflammatory response to injury
(secretory cell-specific). The novel HyperTRIBE (targets of RNA binding proteins identified by editing) technology
allows for the identification of protein-RNA interactions in very small cell populations. I will use this technique to
identify how Msi2 RNA binding targets change in qISCs in response to radiation injury. I will also use MSI2-
HyperTRIBE mice to determine how Msi2-RNA binding partners change in secretory lineage epithelial cells
(Paneth and goblet cells) in response to immune challenge by Yersinia pseudotuberculosis infection.
Furthermore, I will perform in vitro functional assays to assess how Msi2 transcript binding affects translation of
regenerative and immune related candidate mRNAs. Lastly, I will test the functional consequences of Msi loss
on immune function by performing immune activation assays in response to Y. pseudotuberculosis induced
gastritis in Msi1/2 epithelial-specific conditional knockout mice. These studies will provide insight into how Msi2
cell-type specific functions coordinate the regenerative and immune responses to injury in the intestinal
epithelium.

## Key facts

- **NIH application ID:** 10067149
- **Project number:** 1F31AI150224-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Nicolette Johnson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $32,947
- **Award type:** 1
- **Project period:** 2020-08-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10067149

## Citation

> US National Institutes of Health, RePORTER application 10067149, The Msi2 RNA binding protein coordinates epithelial regeneration and the inflammatory response to intestinal mucosal injury (1F31AI150224-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10067149. Licensed CC0.

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