# Integrated Crosstalk of Thin Filament Post-translational Modifications

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2021 · $390,000

## Abstract

PROJECT SUMMARY
Heart failure accounts for approximately 1 out of every 7 deaths in America. Heart failure results in depressed
cardiac systolic contraction and slowed diastolic relaxation, both of which limit heart function and contribute to
disease. Currently there is no therapy to specifically increase myocardial relaxation and improve function of the
failing heart. Myocardial relaxation is mediated by serine/threonine phosphorylation. We have demonstrated
the first tyrosine (Try) phosphorylation identified in the heart directly modulates cardiac muscle function. Our
data demonstrates specific activation of Tyr kinases in living myocardium increase Tyr phosphorylation on the
regulatory protein troponin I (TnI). We further demonstrate increased TnI Tyr phosphorylation beneficially alters
rodent and human cardiac muscle contractile properties key to accelerating myocardial relaxation. These
findings support increasing TnI Tyr phosphorylation in the failing heart as a potential novel target to improve
diastolic dysfunction in heart failure. In this proposal we will employ novel genetic and pharmacological
techniques to define the beneficial accelerated relaxation effects of TnI Tyr phosphorylation as a mechanism
improve in vivo diastolic function of the normal and failing heart and improve survival in heart failure. In addition,
we will begin to translate these beneficial effects of TnI Tyr phosphorylation towards the future development of
a targeted therapy for human heart failure by establishing the relaxation effects of increasing TnI Tyr
phosphorylation in non-failing and failing living human myocardium. The specific outcome of this proposal is to
establish the beneficial effects of TnI Tyr phosphorylation on in vivo heart function of the failing heart and to
translate these functional effects into the human myocardium to establish TnI Tyr phosphorylation as a target
for future heart failure therapy development.

## Key facts

- **NIH application ID:** 10192786
- **Project number:** 5R01HL114940-09
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Brandon J Biesiadecki
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $390,000
- **Award type:** 5
- **Project period:** 2013-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10192786

## Citation

> US National Institutes of Health, RePORTER application 10192786, Integrated Crosstalk of Thin Filament Post-translational Modifications (5R01HL114940-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10192786. Licensed CC0.

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