Monday, June 30, 2025 6/30/2025

The role of energy sensor signaling in mitochondrial cardiomyopathy

Award Number: K08HL145138
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 01/15/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2024

Group Awards By:

View Award Description

The role of energy sensor signaling in mitochondrial cardiomyopathy - ABSTRACT TEXT: Approximately 5.7 million adult Americans have heart failure and this prevalence is projected to increase 25% by 2030. Despite improvement in heart failure treatment, including device therapy and cardiac transplantation, the mortality rate remains high. Cardiac arrhythmia is among the most common cause of mortality in heart failure patients. We and others have demonstrated the roles of mitochondrial dysfunction in heart failure due to various etiologies. Among these, mitochondrial cardiomyopathy demonstrates the most severe impairment of mitochondrial function. Mitochondrial disease is a group of rare genetic disorder due to mutation of mitochondrial proteins, most encoded by nuclear DNA and a few by mitochondrial DNA. Although only approximately 40% of patients with mitochondrial disease exhibit cardiac involvement, the presence of cardiomyopathy significantly predicts poor outcome and to date there is no effective therapy. Novel therapeutics is urgently needed to treat such patients. This study proposes manipulation of energy sensor signaling to enhance mitochondrial function, in order to treat mitochondrial disease, focusing on mitochondrial cardiomyopathy. Our preliminary data and previous publications suggest that energy sensor signaling, including AMP-activated protein kinase (AMPK) and nicotinamide adenine dinucleotide (NAD+), play an important role to maintain mitochondrial function in mitochondrial disease as well as during development of heart failure. This study proposes strategies of manipulating energy sensor signaling (AMPK, NAD+, sirtuin) to improve mitochondrial function and to rescue cardiac arrhythmia in a mouse model of complex I deficiency with mitochondrial cardiomyopathy (Aim 1). To better recapitulate human disease, I propose to model human mitochondrial cardiomyopathy on a dish, using human induced pluripotent cell derived cardiomyocytes with mitochondrial complex I deficiency (Aim 2) and use the same strategies to rescue arrhythmia and cardiomyocyte dysfunction. The training award provides an excellent opportunity to learn novel technology of iPS, gene editing (such as CRISPR/cas), measurement of biomechanics and electrophysiology of cardiomyocytes as functional parameter of “disease in a dish”, and extend my training in mitochondrial biology. This proposal is significant because it advances our scientific understanding of the relationship of mitochondrial dysfunction and heart failure and arrhythmia and test the method to rescue mitochondrial disease. Completion of this study may lead to development of novel therapy for untreatable mitochondrial disease. Finally, since mitochondrial dysfunction is evident in various etiologies of end-stage heart failure, the mitochondrial protective strategies proposed in this study may also be beneficial in other types of heart diseases.


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: 2025 ( Subtotal = -$863 )
2025	2023	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cardiovascular Diseases Research	001	6	2/19/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$2,123
2025	2023	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	000	5	2/19/2025	NON-COMPETING CONTINUATION	-$2,123
2025	2023	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cardiovascular Diseases Research	002	6	4/30/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$863
														Subtotal = -$863

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cardiovascular Diseases Research	001	6	1/13/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$48,600
2024	2023	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	000	5	1/12/2024	NON-COMPETING CONTINUATION	-$48,600
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $160,628 )
2023	2023	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	000	5	12/23/2022	NON-COMPETING CONTINUATION	$160,628
														Subtotal = $160,628

Issue Date FY: 2022 ( Subtotal = $160,628 )
2022	2022	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	000	4	12/24/2021	NON-COMPETING CONTINUATION	$160,628
														Subtotal = $160,628

Issue Date FY: 2021 ( Subtotal = $160,628 )
2021	2021	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	000	3	12/27/2020	NON-COMPETING CONTINUATION	$160,628
														Subtotal = $160,628

Issue Date FY: 2020 ( Subtotal = $160,628 )
2020	2020	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	000	2	12/31/2019	NON-COMPETING CONTINUATION	$152,597
2020	2020	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	001	2	1/31/2020	NON-COMPETING CONTINUATION	$8,031
														Subtotal = $160,628

Issue Date FY: 2019 ( Subtotal = $160,628 )
2019	2019	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	000	1	1/30/2019	NEW	$160,628
														Subtotal = $160,628

Grand Total All Awards = $802,277

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The role of energy sensor signaling in mitochondrial cardiomyopathy

Award Number: K08HL145138

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 01/15/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2024

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer