# Determining the role of REV-ERBs in the SCN and liver circadian hierarchy

> **NIH NIH F32** · UNIVERSITY OF PENNSYLVANIA · 2021 · $65,994

## Abstract

PROJECT SUMMARY/ABSTRACT
The maintenance and synchrony of circadian rhythms throughout the body is essential for metabolic health and
homeostasis. In mammals, the hypothalamic suprachiasmatic nucleus (SCN) acts as the master circadian
regulator, but organs such as the liver possess cell-autonomous clocks that regulate circadian gene expression
in a tissue-specific manner. The REV-ERBα and β nuclear receptors are important components of the
mammalian molecular clock that synchronize metabolic and circadian rhythms. Published data from the Lazar
lab using a REV-ERBα/β hepatocyte double knock-out (HepDKO) mouse suggests that there are distinct sets
of genes in the liver with varying degrees of cell-autonomy. Indeed, hundreds of normally oscillating genes lose
rhythmicity under HepDKO conditions, but a nearly equal number of circadian oscillating genes retained
rhythmicity in HepDKO livers. This implies that these genes have non-cell-autonomous rhythms dictated by
signals from the SCN. There are several proposed SCN-derived outputs that can dictate hepatic rhythmicity,
but innervation via the common hepatic branch (CHB) of the vagus nerve an understudied option. The vagus
nerve is an established mode of communication between the brain and periphery that can integrate circadian
rhythms of fed/fasting state. However, the role of the CHB in relaying circadian signals between the SCN and
liver has yet to be examined. Therefore, I hypothesize that REV-ERB-mediated signals from the SCN clock are
necessary for regulation of genes retained in HepDKO livers and that the CHB acts as an integral
communicator of these regulatory signals. Specific Aim 1 will characterize hepatic physiology and
rhythmicity in a mouse model lacking REV-ERBs in the SCN and liver by knocking out REV-ERBs in the
SCN of HepDKO animals and performing circadian and metabolic phenotyping experiments. I will also collect
tissues from these animals every 3 hours for 24 hours to compare molecular and gene regulatory phenotypes
resulting from REV-ERBs DKO using next generation sequencing (NGS)-based -omics techniques. Specific
Aim 2 will determine the role of the CHB in relaying REV-ERB-mediated circadian signals by severing
the CHB through vagotomy (CHBx) in HepDKO mice. I will perform circadian and metabolic phenotyping
experiments and collect tissues every 3 hours for 24 hours to compare molecular and gene regulatory
phenotypes resulting from CHBx using NGS-based -omics. I predict that the rhythm of gene expression and
regulation as well as behavioral and metabolic rhythmicity in HepDKO mice will be significantly disrupted
without SCN REV-ERBs and in response to CHBx. The experiments outlined herein not only provide significant
advances in the understanding of circadian and metabolic rhythm synchronization but provide substantial
training opportunities for me by utilizing the Lazar lab's unique REV-ERB DKO mouse models and their
expertise in state-of-the-art NGS tools to probe the role of ...

## Key facts

- **NIH application ID:** 10314798
- **Project number:** 1F32DK128984-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Lauren Nicole Woodie
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $65,994
- **Award type:** 1
- **Project period:** 2022-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10314798

## Citation

> US National Institutes of Health, RePORTER application 10314798, Determining the role of REV-ERBs in the SCN and liver circadian hierarchy (1F32DK128984-01A1). Retrieved via AI Analytics 2026-05-30 from https://api.ai-analytics.org/grant/nih/10314798. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*