# Mechanotransduction by Melusin in Cardiac Hypertrophy

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $545,104

## Abstract

PROJECT SUMMARY/ABSTRACT
The goal of the proposed work is to determine if melusin acts as a cardiac-specific mechanotransducer in human
cardiomyocytes leading to hypertrophy, and unravel the mechanisms leading to activation of this pathway.
Myocardial tissue responds to elevated hemodynamic load by hypertrophic growth to increase wall thickness
and thereby reduce wall stress. How these loads are transduced by individual cardiomyocytes in the heart is not
well understood, but melusin (ITGB1BP2), a β1 integrin binding protein, may play an important role. Melusin
forms a signalosome at the costameres of cardiomyocytes and sits at a nexus between two major hypertrophic
pathways, ERK and AKT. We hypothesize that it has an autoinhibitory state due to intramolecular interactions
that hinder its effect in hypertrophic signaling, but this autoinhibition may be attenuated in response to tension.
The specific aims of this proposal will test the effects of melusin on pathological and physiological hypertrophy
in transgenic mice, conduct controllable mechanistic studies in human engineered heart tissue, and examine
whether intramolecular interactions inhibit its assembly at adhesion sites. These studies will elucidate if melusin
plays a role in tension-mediated hypertrophy and verify its response in a human cardiac organoid model and
with bioengineering approaches using human induced pluripotent stem cell derived cardiomyocytes. The health
impact of this work will identify whether melusin is a key player in hypertrophy and provide a detailed
understanding on how melusin affects cardiac growth in response to inherited cardiomyopathies and
hemodynamic overload.

## Key facts

- **NIH application ID:** 10049166
- **Project number:** 1R01HL149734-01A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Nathan John Sniadecki
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $545,104
- **Award type:** 1
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10049166

## Citation

> US National Institutes of Health, RePORTER application 10049166, Mechanotransduction by Melusin in Cardiac Hypertrophy (1R01HL149734-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10049166. Licensed CC0.

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