# Intestinal Stem Cell Function During Aging and Tumor Initiation

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $436,959

## Abstract

PROJECT SUMMARY/ABSTRACT
The intestinal epithelium is a rapidly self-renewing tissue that uses distinct mechanisms for regeneration during
homeostasis and injury-induced repair. Tissue regeneration is supported by heterogeneous cell types including
cycling Lgr5+ intestinal stem cells (ISCs) as well as reserve stem cells set aside for times of injury. We have
recently reported an essential molecular role for Wnt pathway ligands in Lgr5+ ISC maintenance and self-
renewal. We have also developed novel tools for the pharmacological manipulation of the ISC niche. While
adult stem cells serve to maintain and repair tissues for a lifetime, multiple studies have demonstrated that there
is an age-related decline in the regenerative capacity of stem cells across multiple different tissues. Our
preliminary data support diminished regenerative function in ISCs and suggest that these changes are driven by
alterations in the stem cell niche that result in decreased Wnt signaling in the ISCs. We hypothesize that age-
related niche alterations drive the impaired regenerative function of ISCs and these changes are reversible. Our
hypothesis is evaluated by the following Specific Aims: (1) to define how the mesenchymal niche contributes to
functional ISC decline in homeostatic regeneration during aging and (2) to examine ligand-level Wnt pathway
manipulation in the context of colorectal tumor initiation during aging. Achievement of these Aims will provide
insight into exciting new areas of ISC biology, and ultimately lead to improved strategies for tissue repair during
aging.

## Key facts

- **NIH application ID:** 10413255
- **Project number:** 5R01AG067014-03
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Kelley Yan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $436,959
- **Award type:** 5
- **Project period:** 2020-09-30 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10413255

## Citation

> US National Institutes of Health, RePORTER application 10413255, Intestinal Stem Cell Function During Aging and Tumor Initiation (5R01AG067014-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10413255. Licensed CC0.

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