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Troponin I phosphorylation as a novel novel cardiac inotrope

Award Number: R01HL164795
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2023
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Troponin I phosphorylation as a novel novel cardiac inotrope - PROJECT SUMMARY In heart disease, the amount of blood pumped by the heart is not sufficient to supply the metabolic demands of the body. Current positive inotropes (dobutamine, milrinone) increase cardiac contraction by elevating the intracellular calcium contractile signal, however trials have demonstrated this elevated intracellular calcium also causes detrimental arrhythmia, impaired relaxation, and increased mortality rendering this inotropic approach unsuccessful as a long-term therapy. There are currently no approved therapies that directly increase the insufficient function of the heart in disease without long-term detrimental effects. The myofilament protein troponin I (TnI) is critical to relay the calcium activating signal into muscle contraction and is therefore a key regulator of in vivo cardiac muscle function. We have shown the site-specific phosphorylation of TnI increases cardiac muscle contraction without elevating intracellular calcium. Our preliminary data now demonstrates this TnI phosphorylation increases in vivo cardiac function in both normal and diseased hearts without long-term detrimental effects. This proposal will establish the novel effects and mechanism of this TnI site-specific phosphorylation to improve in vivo cardiac function in the normal and diseased mouse heart. We will further establish the effects and safety of this site-specific TnI phosphorylation on human cardiac tissue towards establishing this phosphorylation as a future therapeutic approach in human heart disease.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $618,446 )
2026	2026	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	001	4	3/23/2026	NON-COMPETING CONTINUATION	$18,931
2026	2026	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	000	4	3/10/2026	NON-COMPETING CONTINUATION	$599,515
														Subtotal = $618,446

Issue Date FY: 2025 ( Subtotal = $631,068 )
2025	2025	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	000	3	3/28/2025	NON-COMPETING CONTINUATION	$567,962
2025	2025	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	001	3	7/24/2025	NON-COMPETING CONTINUATION	$63,106
														Subtotal = $631,068

Issue Date FY: 2024 ( Subtotal = $700,742 )
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	000	2	3/8/2024	NON-COMPETING CONTINUATION	$643,540
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	001	2	6/20/2024	NON-COMPETING CONTINUATION	$57,202
														Subtotal = $700,742

Issue Date FY: 2023 ( Subtotal = $671,237 )
2023	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	000	1	3/31/2023	NEW	$671,237
														Subtotal = $671,237

Grand Total All Awards = $2,621,493

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Troponin I phosphorylation as a novel novel cardiac inotrope

Award Number: R01HL164795

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/01/2023

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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