# The Role of Chromatin in Metabolic Homeostasis

> **NIH NIH R35** · STANFORD UNIVERSITY · 2020 · $412,208

## Abstract

The coordination of cellular function with the environment is essential for adaptation and survival. For
example, cells have remarkable ability to sense diverse (i.e. nutrient-rich or -limiting) environments and
reprogram their energy metabolism and proliferative capacity accordingly. Dynamic nutrient environments are
ubiquitous throughout nature and include competitive growth environments of proliferating microorganisms and
tissue niches in multicellular organisms. Failure to adapt can lead to cell death, developmental defects, and
disease. Indeed, energy metabolism alterations are a major contributing factor for many pathologies, including
cancer, cardiovascular disease, and diabetes, which together account for two-thirds of all deaths in the U.S.
 Adaptive cellular responses are often achieved by rapid inducible changes in gene expression
programs. An ideal mechanism to achieve this is through modification of chromatin. Despite this knowledge,
the mechanisms by which chromatin modification contributes to metabolic plasticity remain largely unexplored.
Indeed, many broad biological questions remain unanswered: Is energy metabolism flexibility facilitated
through chromatin regulation of metabolic gene expression? How are nutrient sensing pathways connected to
the function of these chromatin regulators? Does chromatin-regulated metabolic gene expression influence
commitment to cell division? Do these chromatin modifiers influence energy metabolism plasticity required
during developmental programming.
 Our preliminary data suggests chromatin remodelers, which regulate transcription by (re)positioning
nucleosomes, are central components of metabolic signaling pathways. Disruption of chromatin remodeling
results in defects in metabolic gene expression, oxygen consumption, cell division, and embryonic
development. Our central hypothesis is that chromatin modifiers link nutrient sensing pathways to
metabolic gene regulation required for fitness, proliferation and development. Our broad research goal
is to define chromatin modifications events that coordinate metabolic plasticity and are central to adaptive
cellular responses. Our varied experimental approach is innovative because it leverages the power of diverse
eukaryotic model systems, namely yeast and mice, to investigate fundamental conserved metabolic pathways
within different biological contexts. Through achievement of our research goal we expect the following
outcomes: Identification of novel epigenetic regulators of energy metabolism; determination of the relationship
between nutrient sensing pathways and chromatin; recognition of the chromatin-regulated metabolic
requirements for cell division; determination of chromatin modification required for energy metabolism during
development. Our proposed research is significant because it will establish chromatin modifiers as necessary
components of metabolic homeostasis, and serve as a platform to investigate epigenetic regulation of
metabolic func...

## Key facts

- **NIH application ID:** 9938583
- **Project number:** 5R35GM119580-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Ashby J. Morrison
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $412,208
- **Award type:** 5
- **Project period:** 2016-08-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9938583

## Citation

> US National Institutes of Health, RePORTER application 9938583, The Role of Chromatin in Metabolic Homeostasis (5R35GM119580-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9938583. Licensed CC0.

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