# Metabolic and epigenetic drivers of stem cells in obesity and cancer

> **NIH NIH K22** · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · 2020 · $177,149

## Abstract

Project Abstract
Title: Metabolic and epigenetic drivers of stem cells in obesity and cancer
PI: Miyeko Mana
Our understanding of the relationship between diet, stem cells, and cancer is central to the prevention and
treatment of this disease. With rising levels of obesity and the associated risk of cancer there is greater need to
understand mechanisms by which diet influences tissue-specific stem cells that lead to oncogenic
transformation. We have shown that a pro-obesity high-fat diet (HFD) increases stem cell number and niche
independent growth in the mammalian intestine. We demonstrated that a HFD promotes stem cell self-renewal
and tumorigenesis through the activation of a robust peroxisome proliferator-activated receptor delta (PPAR-δ)
signature. Importantly, we showed these properties were bestowed upon the progenitor population thereby
expanding the pool of cells capable of malignant growth. Our preliminary results indicate that multiple members
of the PPAR family are required to establish the HFD phenotype in intestinal stem cells, and that PPAR
redundancy signals the importance of downstream effectors. The biochemical and molecular underpinnings of
the HFD will emerge through identification of the mechanistic steps that alter basic metabolism and epigenetic
maintenance of the HFD transcriptional state. Our overall hypothesis is that a HFD markedly influences the
metabolism and the stability of a PPAR transcriptional program that impact intestinal stem cells, tumor initiation
and progression. We will test the premise that (Aim1) a HFD or agonist-activated PPAR establishes a state of
dependency on the metabolic fatty acid oxidation program, and (Aim2) a HFD induces a stable transcriptional
state by perturbing the chromatin landscape through chronic PPAR activity.

## Key facts

- **NIH application ID:** 9805523
- **Project number:** 1K22CA241083-01
- **Recipient organization:** ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
- **Principal Investigator:** Miyeko Mana
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $177,149
- **Award type:** 1
- **Project period:** 2020-08-16 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9805523

## Citation

> US National Institutes of Health, RePORTER application 9805523, Metabolic and epigenetic drivers of stem cells in obesity and cancer (1K22CA241083-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9805523. Licensed CC0.

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