# Metabolic regulation of intestinal stem cell homeostasis

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2022 · $445,920

## Abstract

Summary
Many cancer and stem cells exhibit a metabolic program that is distinct from most terminally differentiated
cells, wherein a smaller fraction of the glycolytic product pyruvate is transported into the mitochondria and
oxidized. Through a recent collaborative study, the Rutter and Thummel laboratories recently discovered the
identity of the transporter, known as the Mitochondrial Pyruvate Carrier (MPC), which mediates mitochondrial
pyruvate entry. Having made this breakthrough, we are now in position to test the hypothesis, first proposed
about 40 years ago, that loss of the MPC underlies a portion of the decreased mitochondrial pyruvate oxidation
observed in cancers. We have generated significant preliminary data in support of this hypothesis for colon
cancers, and our data suggests that intestinal stem cells might exhibit the same phenomenon. We propose to
employ a multi-system approach, similar to the one that enabled the initial discovery of the MPC, that uses the
powerful strengths of intestinal organoid culture, Drosophila melanogaster, and mouse models of cancer and
intestinal homeostasis. Utilizing this approach, we intend to test the hypothesis that mitochondrial pyruvate
oxidation is necessary and sufficient to maintain appropriate stem cell homeostasis and can play an instructive
role in colon oncogenesis. We will do this through three specific aims that define the mechanistic basis for the
regulation and function of the MPC in instructing intestinal stem cell fate and the propensity of oncogenesis as
well as define the impact of those mechanisms in intact animal models. This information will establish a new
framework for understanding how core metabolic pathways can directly impact the initiation and progression of
colon tumors.

## Key facts

- **NIH application ID:** 10463558
- **Project number:** 5R01CA228346-05
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Jared P Rutter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $445,920
- **Award type:** 5
- **Project period:** 2018-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463558

## Citation

> US National Institutes of Health, RePORTER application 10463558, Metabolic regulation of intestinal stem cell homeostasis (5R01CA228346-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10463558. Licensed CC0.

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