# Regulation of cardiac power output in health and disease

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $535,057

## Abstract

Project Summary/Abstract
 Familial cardiomyopathies are the leading cause of sudden death in people under 30. Two closely related
cardiomyopathies, hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are characterized by
remodeling of the tissue in the ventricular wall, often accompanied by fibrosis, and myocyte disarray. These
diseases are primarily caused by mutation of the proteins involved in generating or regulating power output by
the heart. It has been proposed that HCM is caused by hypercontractility at the molecular level while DCM is
caused by hypocontractility at the molecular level; however, it is not clear how mutations at the molecular level
lead to alterations in the contractility and structure of heart cells and tissues. The goal of this research is to
better understand the connections between molecular-based changes and the changes in contractility and
structure at the cellular and tissue levels. To do this, we will harness biophysical, biochemical, cell biological,
and tissue engineering techniques to measure contractility across these scales of organization, and then use
mathematical modeling to connect these observations. We will examine two model mutations in troponin-T that
cause either HCM or DCM. In Aim 1, we will dissect the molecular mechanism of two mutations in cardiac
troponin-T, R92Q and K210, that cause hypercontractility and hypocontractility at the molecular level,
respectively. In Aim 2, we will dissect the effects of these mutations on the structural and contractile properties
of stem cell derived cardiomyocytes and engineered tissues. In Aim 3, we will examine whether these mutations
affect the ability of cells and tissues to sense and respond to their mechanical environment. This bottom up
approach will give unprecedented insights into the mechanisms of cardiac force production, mechanosensing by
the heart, and the disease pathogenesis of familial cardiomyopathies.

## Key facts

- **NIH application ID:** 9910443
- **Project number:** 5R01HL141086-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Michael J Greenberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $535,057
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9910443

## Citation

> US National Institutes of Health, RePORTER application 9910443, Regulation of cardiac power output in health and disease (5R01HL141086-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9910443. Licensed CC0.

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