# Understanding the role of Myosin 5b in liver metabolism

> **NIH NIH R03** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2024 · $113,250

## Abstract

Project Summary
Myosin 5b is responsible for transporting key apical proteins to the surface of epithelial cells. Myosin 5b is most
widely studied because of its association with Microvillus Inclusion Disease, a congenital diarrhea disorder in
which inactivating mutations in Myosin 5b is a primary cause. Individuals with Microvillus Inclusion Disease
frequently present with cholestasis in addition to their intestinal defects; indicating potential alterations in liver
function arising from loss of Myosin 5b. Data acquired under my NIDDK K01 career development award
demonstrates that germline Myosin 5b knockout mice exhibit alterations in liver function in terms of polarity and
bile acid profiles. We also observed that Myosin 5b knockout mice had lipid accumulation and altered
mitochondrial function which suggests that Myosin 5b has diverse roles in liver metabolism. This R03 proposal
seeks to build upon findings from my K01 award and identify the role of Myosin 5b in regulating liver metabolism.
The central hypothesis of this research proposal is that Myosin 5b transports and positions lipids, glycogen stores
and mitochondria within hepatocytes. We propose that in the absence of Myosin 5b lipids and glycogen stores
are immobilized preventing the proper process of these molecules. Additionally, we postulate that Myosin 5b
regulates mitochondria dynamics and function. We base our hypothesis on preliminary data generated from our
mouse model which shows changes in lipids, glycogen stores and mitochondria in the liver of Myosin 5b knockout
mice compared to littermate control mice. Liver organoids generated from Myosin 5b knockout mice exhibited
decreased oxygen consumption rates compared to control organoids demonstrating decreased mitochondrial
function. For this R03 application, we propose to use germline Myosin 5b knockout mice to address deficits in
lipid metabolism, glycogen mobilization and mitochondria in vivo and in vitro. Specific Aim 1 will define changes
in lipid and glycogen in hepatocytes resulting from loss of Myosin 5b. Specific Aim 2 will determine the role of
Myosin 5b in regulating liver mitochondrial function. We will use cutting edge research techniques including high
resolution confocal imaging, live imaging of liver organoids as well as metabolic profiling. At the completion of
these studies, we expect to have elucidated the role of Myosin 5b in the regulation of metabolic pathways in
hepatocytes. Funding of this R03 proposal would provide support and new preliminary data to base a NIDDK
R01 application. Additionally, this project will provide new research avenues for my lab that are very distinct from
my postdoctoral work and my postdoctoral mentor’s scientific interests. This R03 proposal highlights the need
for a better understanding of the function of Myosin 5b within the liver and in regulating pathways that have
historically not been linked to Myosin 5b.

## Key facts

- **NIH application ID:** 10871154
- **Project number:** 1R03DK139282-01
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Amy C Engevik
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $113,250
- **Award type:** 1
- **Project period:** 2024-05-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10871154

## Citation

> US National Institutes of Health, RePORTER application 10871154, Understanding the role of Myosin 5b in liver metabolism (1R03DK139282-01). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10871154. Licensed CC0.

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