# The Role of Lpcat3 and Phospholipid Remodeling in Intestinal Homeostasis

> **NIH NIH K01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2022 · $165,005

## Abstract

PROJECT SUMMARY
Intestinal homeostasis is controlled by a strict balance between cell proliferation in the crypts and cell shedding
from the villi. Dysregulation of intestinal homeostasis is known to cause severe intestinal pathologies, including
inflammatory bowel diseases (IBD) and gastrointestinal cancer. Although much progress has been made
towards understanding how this complex epithelial system maintains homeostasis, whether and how lipid
metabolism may influence the epithelial cells along the crypt-villus axis during homeostatic and diseased states
has been largely unexplored. Recent studies from our lab has identified critical functions of
lysophosphatidylcholine acyltransferase 3 (Lpcat3), a phospholipid (PL) remodeling enzyme, in intestine. Loss
of Lpcat3 in intestine selectively reduces polyunsaturated phosphatidylcholine (PC) in membranes, leading to
decreased membrane fluidity and curvature, and impaired lipid absorption. Our following studies discovered that
Lpcat3 and PL remodeling also play important roles in intestinal stem cell (ISC) proliferation and the maintenance
of homeostasis. However, the mechanisms by which Lpcat3 affects intestinal homeostasis are not clear.
The primary aim of this proposal is to understand how Lpcat3 and phospholipid remodeling regulate ISC
proliferation and intestinal homeostasis. Aim 1 will examine if Lpcat3 deficiency affects proliferation and
differentiation of ISCs, and test if different PC species regulate crypt proliferation using ex vivo crypt organoid
culture. Aim 2 will unravel the mechanisms by which loss of Lpcat3 promotes crypt proliferation. Aim 3 will
determine if PC remodeling and cholesterol metabolism may contribute to intestinal tumorigenesis.
The candidate has a background in lipid metabolism and cancer biology. His long term scientific goal is to unravel
the molecular mechanisms underlying lipid metabolism and human diseases. To further prepare himself for his
long-term research goal, he plans to seek training that will complement his existing technical skills and further
develop his professional skills. UCLA has a highly collaborative environment ideal to this project and for him to
achieve these goals. His mentor, Dr. Peter Tontonoz, is a highly respected scientist with expertise in the areas
of nuclear receptors, inflammation and lipid metabolism. The applicant also has an advisory committee that
consists of Dr. Martin G Martín, an accomplished gastrointestinal biologist and expert in intestinal stem cell
biology, Dr. Steve Bensinger, an internationally recognized expert in lipid metabolism/mass spectrometry, and
Dr. Stephen Young, a pioneer and expert in lipid metabolism in intestine. His mentor team has a detailed plan
to facilitate his research progress and scientific career development. In summary, his educational and research
experience together with a strong and supportive mentoring team make him an ideal candidate for this research
project and the K01 award.

## Key facts

- **NIH application ID:** 10333366
- **Project number:** 5K01DK114373-05
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Bo Wang
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $165,005
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10333366

## Citation

> US National Institutes of Health, RePORTER application 10333366, The Role of Lpcat3 and Phospholipid Remodeling in Intestinal Homeostasis (5K01DK114373-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10333366. Licensed CC0.

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