# Regulation of atrial contractility in cardiomyopathy

> **NIH NIH R56** · LOYOLA UNIVERSITY CHICAGO · 2022 · $596,739

## Abstract

PROJECT SUMMARY
Cardiomyopathies are a group of diseases, commonly with genetic causes, that impairs cardiac function and
can lead to heart failure. The focus of cardiomyopathy research has been left ventricular function, as this
chamber is critical for supporting life, but the whole heart is typically affected by these diseases. The cardiac
atria provide many functional roles in regulating cardiac function and have a gene expression profile that allows
them to fulfil their specific function. We provided evidence that mutations in myosin binding protein H-like
(MyBP-HL), a protein that is specifically expressed in the atria, is linked with dilated cardiomyopathy and
arrhythmias in humans and mice. This protein is highly related to the carboxy terminal domains of the well-
studied protein cardiac myosin binding protein-C (cMyBP-C), dysfunction in which is highly associated with the
development of cardiomyopathy. We identified that both these proteins compete for a discrete number of
myosin binding sites and maintain a ~1:1 ratio in human and mouse atria. We hypothesize that missense
mutations in the myosin binding domains of these two proteins disrupts stoichiometry of these proteins and
leads to atrial myopathy and overall cardiac dysfunction. We propose to model these mutations in human
induced pluripotent stem cell derived cardiomyocytes and assess the effect of binding on the stoichiometry of
these two proteins. We will use these cells to model different levels of each myosin binding protein and
generate engineered heart tissue that we will assess for alterations in contractile kinetics.

## Key facts

- **NIH application ID:** 10687398
- **Project number:** 1R56HL165137-01
- **Recipient organization:** LOYOLA UNIVERSITY CHICAGO
- **Principal Investigator:** David Y Barefield
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $596,739
- **Award type:** 1
- **Project period:** 2022-09-13 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10687398

## Citation

> US National Institutes of Health, RePORTER application 10687398, Regulation of atrial contractility in cardiomyopathy (1R56HL165137-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10687398. Licensed CC0.

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