# The Role of Wnt2b in Intestinal Health

> **NIH NIH K08** · BOSTON CHILDREN'S HOSPITAL · 2022 · $168,005

## Abstract

Project Summary
 Wnt signaling has been shown to be critical for intestinal health, and Wnts are required for
intestinal stem cell (ISC) homeostasis. The roles of individuals Wnts in ISC regulation remain poorly
defined. We have recently described a human congenital diarrheal disorder caused by deficiency of
Wnt2b, marked by intestinal inflammation and loss of Lgr5+ISC, showing that Wnt2b is critical in the
intestine. The goal of this proposed project is to clarify the need for Wnt2b in intestinal health. In Aim
1 we will investigate whether there is a developmental requirement for Wnt2b using mouse and
human developmental models. In Aim 2 we will examine the impact of human Wnt2b on Lgr5+ISC
homeostasis using a more mature enteroid model. We will also consider the mesenchymal versus
epithelial sources of Wnt2b as components of Aims 1 and 2.
 This proposal is a five-year, mentored career development plan focused on expanding the
investigator's knowledge of mucosal development and intestinal stem cell biology, as well as
providing in depth instruction on genome editing and organogenesis techniques. The candidate is an
MD/PhD trained physician scientist who is also an allergist/immunologist and neonatologist, and
currently practices as a neonatologist at Boston Children's Hospital. The proposal will build on her
strong immunology background by adding new expertise in stem cell biology and translational
investigation through the tutelage of her co-mentors, Dr. Pankaj Agrawal and Dr. David Breault at the
Manton Center for Orphan Disease Research and the Harvard Digestive Disease Center of Boston
Children's Hospital. The proposed work will result in the candidate building niche expertise on
regulators of intestinal development, upon which she plans to build her independent research career.

## Key facts

- **NIH application ID:** 10312111
- **Project number:** 5K08DK120871-03
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Amy E OConnell
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $168,005
- **Award type:** 5
- **Project period:** 2020-01-15 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10312111

## Citation

> US National Institutes of Health, RePORTER application 10312111, The Role of Wnt2b in Intestinal Health (5K08DK120871-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10312111. Licensed CC0.

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