# Phosphoglycerate mutase 5 (PGAM5) in the regulation of hepatic lipid metabolism and carcinogenesis

> **NIH NIH P20** · LOUISIANA STATE UNIV A&M COL BATON ROUGE · 2022 · $221,819

## Abstract

Summary: PGAM5 in the regulation of hepatic lipid metabolism and carcinogenesis
(PI: Andrea Johnston, DVM, PhD).
The broad objective of this project is to determine whether changes in mitochondrial metabolism
mechanistically influence the transition from non-alcoholic fatty liver disease (NAFLD) to
hepatocellular carcinoma (HCC). NAFLD is emerging as a leading cause of HCC. HCC survival
outcomes are poor. Defining the bioenergetic pathophysiology of NAFLD and its progression to
HCC will identify new biomarkers and therapeutic targets. The mitochondrial membrane protein
phosphoglycerate mutase 5 (PGAM5) regulates an array of mitochondrial homeostatic pathways.
Recent research shows that depletion of PGAM5 prevents both high fat diet (HFD) induced
obesity and the progression of HCC. The proposed research will test the hypothesis that distinct
mitochondrial metabolic pathways are responsible for these effects. A liver specific knockout
mouse will be generated to determine whether hepatocyte specific loss of PGAM5 will inhibit
steatosis in a HFD model. Single cell RNA sequencing of a human HCC cell line will determine if
PGAM5 depletion alters gene expression associated with hepatic lipid metabolism. HCC
spheroids will be used to characterize how loss of PGAM5 modulates mitochondrial respiration
and glycolysis in a steatosis model. Two specific aims are proposed: Aim 1 will determine whether
PGAM5 knockout inhibits hepatocellular steatosis. Aim 2 will determine whether PGAM5 deletion
alters mitochondrial metabolism in HCC leading to increased reactive oxygen species production.

## Key facts

- **NIH application ID:** 10360598
- **Project number:** 5P20GM135000-02
- **Recipient organization:** LOUISIANA STATE UNIV A&M COL BATON ROUGE
- **Principal Investigator:** Andrea Noel Johnston
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $221,819
- **Award type:** 5
- **Project period:** 2021-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10360598

## Citation

> US National Institutes of Health, RePORTER application 10360598, Phosphoglycerate mutase 5 (PGAM5) in the regulation of hepatic lipid metabolism and carcinogenesis (5P20GM135000-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10360598. Licensed CC0.

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