Tuesday, November 4, 2025 11/4/2025

Biophysical Modulation of Cardiac Ion Channels by MicroRNA

Award Number: R01HL139006
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2017
PERIOD OF PERFORMANCE END DATE: 04/30/2027

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Biophysical Modulation of Cardiac Ion Channels by MicroRNA - Project Summary MicroRNAs (miRs) are evolutionally conserved small non-coding RNA molecules that are broadly involved in regulating most biological events; previous studies have focused on the canonical mRNA interference (RNAi) mechanism of miRs. During the previous funding period, we were the first to unveil an evolutionarily- conserved novel biophysical action for miRs beyond its RNAi mechanism. Specifically, we revealed a novel biophysical action of miR1, which is the most predominant miR in the heart and is downregulated in human heart failure. We found that miR1 physically binds to an inward rectifier potassium channel Kir2.1, directly suppresses the IK1 current and biophysically modulates cardiac cellular electrophysiology. Importantly, we found that a human single nucleotide polymorphism (hSNP) of miR1–– hSNP14A/G (rs776480338), in which the 14th nucleotide “A” is mutated to “G”, is a RNAi-only variant that specifically abolishes the biophysical action while maintaining the RNAi function of miR1, validating that the biophysical modulation is independent of RNAi. Our discoveries suggest that miRs modulate cardiac homeostasis through two different mechanisms: 1) canonical RNAi that regulates the expression of proteins, including ion channels, and 2) newly-discovered mechanism of direct binding with proteins that quickly results in functional modulation. With this important new finding, it is now imperative to investigate if multiple cardiac ion channels are biophysically modulated by miRs and to elucidate the specific physiological impact of miR1’s biophysical action in the regulation of cardiac (electro)physiology. Based on our published findings and preliminary data, we hypothesize that the biophysical modulation of cardiac ion channels by miRs is a general regulatory mechanism that exists broadly and plays a critical role in the homeostasis of the heart. We will study this with the following specific aims. 1) To investigate the biophysical modulation of cardiac ion channels by miR1, 2) To understand the physiological impact of miRs’ biophysical action on the heart, 3) To unveil the general mechanisms guiding miRs’ biophysical modulation of cardiac ion channels. In addition to a broad range of cellular activities regulated by the large number of miRs (>30,000 miRs in >200 species) and ion channels, our study will significantly and innovatively expand the biological significance of miR biology and ion channel biology with broad implications. Our discoveries have pioneered a new field in miR biology and will provide a mechanistic foundation and new avenue of RNA-medicine development for antiarrhythmic therapy.


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 = $651,378 )
2025	2025	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	002	7	5/27/2025	NON-COMPETING CONTINUATION	$651,378
2025	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	001	5	2/18/2025	COMPETING CONTINUATION	$202
2025	2020	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	000	4	2/18/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$202
														Subtotal = $651,378

Issue Date FY: 2024 ( Subtotal = $638,349 )
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	000	6	4/16/2024	NON-COMPETING CONTINUATION	$586,240
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	001	6	6/12/2024	NON-COMPETING CONTINUATION	$52,109
														Subtotal = $638,349

Issue Date FY: 2023 ( Subtotal = $651,378 )
2023	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	001	5	4/25/2023	COMPETING CONTINUATION	$651,378
2023	2020	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	000	4	4/12/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $651,378

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	000	4	6/1/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2020	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	002	4	3/9/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$738,150
2021	2019	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Cardiovascular Diseases Research	001	3	3/9/2021	NON-COMPETING CONTINUATION	-$635,003
2021	2018	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Cardiovascular Diseases Research	000	2	3/9/2021	NON-COMPETING CONTINUATION	-$103,147
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $619,298 )
2020	2020	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cardiovascular Diseases Research	001	4	5/14/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$619,298
2020	2019	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Cardiovascular Diseases Research	000	3	5/12/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $619,298

Issue Date FY: 2019 ( Subtotal = $635,003 )
2019	2019	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Cardiovascular Diseases Research	000	3	7/11/2019	NON-COMPETING CONTINUATION	$635,003
														Subtotal = $635,003

Issue Date FY: 2018 ( Subtotal = $634,826 )
2018	2018	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Cardiovascular Diseases Research	000	2	6/19/2018	NON-COMPETING CONTINUATION	$634,826
														Subtotal = $634,826

Issue Date FY: 2017 ( Subtotal = $634,653 )
2017	2017	CASE WESTERN RESERVE UNIVERSITY	10900 EUCLID AVE	CLEVELAND	OH	44106	CUYAHOGA	USA	Cardiovascular Diseases Research	000	1	5/26/2017	NEW	$634,653
														Subtotal = $634,653

Grand Total All Awards = $4,464,885

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Biophysical Modulation of Cardiac Ion Channels by MicroRNA

Award Number: R01HL139006

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2017

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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