# Identification and Characterization of Novel Metabolic Regulators in Mouse and Human Liver

> **NIH NIH K22** · TEMPLE UNIV OF THE COMMONWEALTH · 2020 · $238,518

## Abstract

Project Summary/Abstract
The long non-coding RNAs (lncRNAs) are an emerging and rapidly-growing class of functional genomic elements,
and a number have been shown to regulate fundamental biological processes, but the scope of their influence
in metabolic disorders remains unknown. Identifying and characterizing metabolically-relevant lncRNAs will be
crucial to obtaining a better understanding the pathophysiology of obesity and other diseases of metabolism.
The candidate aspires to contribute to this understanding by studying novel metabolic regulators, while
developing additional experience in relevant research techniques and receiving the necessary career
development training to transition to a role as an independent principal investigator.
Expanding on the candidate’s recent genome-wide screen that identified 140 lncRNAs and 239 mRNAs sensitive
to metabolic conditions in mouse liver, the proposed research will study the roles of one novel lncRNA, Gm15441,
in regulating triglyceride (TG) and cholesterol metabolism (Aim 1) and one novel protein-coding gene, Rab30, in
regulating autophagy, free fatty acid (FFA) oxidation, and TG secretion in mouse livers (Aim 2). The mechanism
by which Gm15441 regulates TG and cholesterol metabolism will be defined by exploring its cis-regulation of the
overlapping metabolically-relevant protein-coding gene. In preliminary experiments, knockdown of Rab30
affected autophagy and lipid metabolism in fasting mouse livers, therefore the role of Rab30 in membrane
trafficking will be determined. Additionally, the comprehensive bioinformatics analysis pipeline established in the
recent genome-wide screen will be applied to human liver samples, to identify novel lncRNA metabolic regulators
in human liver (Aim 3). The efficacy of this pipeline for predicting the function of human genes was established
in preliminary experiments by testing known metabolic genes, such as G6PC (glucose-6-phosphatase catalytic
subunit), which was correctly predicted to function in gluconeogenesis.
A K22 award will offer this candidate the opportunity to develop new skills in CRISPR, confocal microscopy, cell
biology, and bioinformatics. The candidate will develop these skills while developing experience in pursuing
research of translational significance. Gm15441, for instance, is localized in a region that is syntenic with the
human 1q21-23 locus, implicated in type 2 diabetes mellitus and familial combined hyperlipidemia. The candidate
has developed a comprehensive plan for the development of her career, has identified coursework that will confer
necessary skills for success as an independent investigator, and has secured a team of distinguished mentors
and advisors who will support her throughout her career transition. Successful completion of the work described
in this proposal could provide critical insight into the regulatory networks of hepatic and systemic metabolism,
and will afford the candidate the ability to achieve research independ...

## Key facts

- **NIH application ID:** 9984514
- **Project number:** 5K22HL139921-03
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Ling Yang
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $238,518
- **Award type:** 5
- **Project period:** 2018-08-15 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984514

## Citation

> US National Institutes of Health, RePORTER application 9984514, Identification and Characterization of Novel Metabolic Regulators in Mouse and Human Liver (5K22HL139921-03). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9984514. Licensed CC0.

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