# Role of Cardiac Troponin in Health and Disease

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2020 · $377,570

## Abstract

Project Summary/Abstract
 We have smartly formulated a large collection of novel TnCs to enhance or reduce cardiac muscle
contractility in vivo. Using gene therapy approaches, we will test whether these engineered proteins can be
used as novel therapies against a wide spectrum of acquired and inherited cardiac diseases. Specifically, we
have developed a novel approach to enhance cardiac muscle contractility without compromising relaxation or
making the heart an arrhythmic substrate. We have also engineered a novel approach to reduce
hypercontractility of a diseased heart and enhance its relaxation. Furthermore, these studies will establish the
potential of using engineered TnCs as a therapeutic tool to help patients suffering from several different
cardiovascular diseases.
 We recently demonstrated that our smartly formulated L48Q TnC therapeutically increases in vivo
cardiac contractility, function and performance after an MI. Our new exciting preliminary data demonstrates
that cardiac contractility, function and performance can also be enhanced by L48Q TnC following a transverse
aortic constriction (TAC; pressure overload on the left heart), without compromising relaxation/diastolic
function. The purpose of this proposal is multifold and will: 1) demonstrate the broader therapeutic impact
and clinical relevance of our smartly formulated TnCs on cardiovascular diseases with vastly different
etiologies; 2) determine whether increasing contractility preserves cardiac function and performance of the
right heart in pulmonary hypertension and the left heart in TAC; and 3) determine whether our smartly
formulated TnCs can be used to combat inherited restrictive, hypertrophic and dilated cardiomyopathies.
Aim 1. Determine if our smartly formulated TnCs can improve heart function in right and left sided
he art failure .
 Pressure overload of the right and left heart are common and devastating diseases that compromise
cardiac function and performance. Our battery of examinations will thoroughly test if cardiac muscle
contractility can be tuned from the myocyte to in vivo by our novel engineered TnCs to combat left and right
heart pressure overload.
Aim 2. Determine if smartly formulated TnCs can improve heart function in inherited 
cardiomyopathies that  model the  human diseases.
 Inherited cardiomyopathies also compromise the contractility of the heart. We will test if smartly
formulated TnCs can be used to combat these diverse cardiac diseases and improve the in vivo function and
performance of the heart. The completion of this proposal will establish the potential of our novel translational
strategies to help combat a broad range of cardiovascular diseases.

## Key facts

- **NIH application ID:** 9840924
- **Project number:** 5R01HL132213-04
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Jonathan Paul Davis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $377,570
- **Award type:** 5
- **Project period:** 2016-12-15 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9840924

## Citation

> US National Institutes of Health, RePORTER application 9840924, Role of Cardiac Troponin in Health and Disease (5R01HL132213-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9840924. Licensed CC0.

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