# RNA modification in cardiometabolic disease

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $559,709

## Abstract

PROJECT SUMMARY
Perturbations in metabolic pathways form the epicenter of some of the most devasting threats to mankind,
including cardiovascular disease, obesity and NASH. Proper maintenance of metabolic homeostasis requires
precise and synchronized control of gene regulation. Recently, the discovery that thousands of mammalian
RNAs undergo chemical modifications that powerfully impacts transcript dynamics expands our understanding
of gene regulatory mechanisms. N6-methyladenosine methylation (m6A) is the most common internal RNA
modification. Multiple lines of evidence suggest that m6A plays a critical role in organismal biology, including
stem cell renewal, however, the impact of chemical modifications on RNA in metabolic control is less well
understood. The objective of this proposal is to define the physiologic contribution and mechanisms of RNA
modifications in metabolism. Capitalizing on our preliminary studies showing that the hepatic m6A landscape is
altered in response to diet and strongly enriches lipogenic RNAs, we hypothesize that dynamic RNA
modifications are essential for tight regulation of hepatic lipid metabolism. Reinforcing this premise, our studies
show that liver-specific knockout of m6A installing machinery leads to increased lipogenesis and alterations in
hepatic lipid composition. In aim1, we investigate the function of m6A in hepatic lipid metabolism and fatty liver
disease as well as explore opportunities for RNA modification based therapeutic strategies in metabolic
disease. In aim2, we define how m6A modifications impact lipogenesis and decipher the hierarchical and
cooperative relationship between m6A modifying enzymes and canonical metabolic transcriptional modulators.
Our proposed studies are expected to shed fundamental insight into novel mechanisms involved in metabolic
control and a model by which RNA modifications can impact health and disease states. In summary, our
studies identify a new pathway for lipid degradation and in this application, we propose a series of molecular,
cell biological, and animal studies to extend our preliminary observations and test out hypothesis.

## Key facts

- **NIH application ID:** 10295370
- **Project number:** 1R01DK127232-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Tamer Sallam
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $559,709
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10295370

## Citation

> US National Institutes of Health, RePORTER application 10295370, RNA modification in cardiometabolic disease (1R01DK127232-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10295370. Licensed CC0.

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