Tuesday, July 1, 2025 7/1/2025

Cilia and Valvular Heart Disease

Award Number: R01HL131546
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2016
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Cilia and Valvular Heart Disease - PROJECT SUMMARY Based on genetic and cellular discoveries made in the PI lab and his collaborators, this proposal focuses on novel mechanisms that are critical for formation of heart valves. Data presented in the proposal are an evolution of our studies presented in the first round of funding and show that mutations in the DZIP1 gene cause a very common heart valve disease (i.e., mitral valve prolapse) and can be caused by errors in how valve tissue forms during development. These discoveries have led to a novel concept that cilia are involved in valve development. While the function of DZIP1 is a focus of our studies in this proposal, we will also define new mechanisms by which the cardiac valves establish a trilaminar ECM organization and how this can feed back to the cells to suppress ciliogenesis in specific regions of the valve. Our studies will provide unique opportunities to answer questions about heart-valve diseases that heretofore have been impossible to answer using even state-of-the- art biological and genetic approaches. Valvular heart disease is a serious clinical problem, affecting 5-7% of the human population. Its complications include congestive heart failure, endocarditis, atrial arrhythmias, and sudden death. There are no known non- surgical cures for this group of disease. The proposed work capitalizes on previously unrecognized genetic data collected from heart valve disease patients; studies in the mouse show that this class of genes is an important and previously unrecognized contributor to valve structural development and disease pathogenesis. The uncovering of this particular disease gene and the processes it regulates holds great potential for future remedial or therapeutic insight towards regeneration or formation of mechanically stable valve tissue that will be beneficial to valvular heart disease patients.


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 = $514,275 )
2025	2025	THE MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Cardiovascular Diseases Research	000	8	3/14/2025	NON-COMPETING CONTINUATION	$514,275
														Subtotal = $514,275

Issue Date FY: 2024 ( Subtotal = $559,990 )
2024	2024	THE MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Cardiovascular Diseases Research	001	7	6/20/2024	NON-COMPETING CONTINUATION	$45,715
2024	2024	THE MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Cardiovascular Diseases Research	000	7	3/8/2024	NON-COMPETING CONTINUATION	$514,275
														Subtotal = $559,990

Issue Date FY: 2023 ( Subtotal = $1,142,727 )
2023	2023	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Cardiovascular Diseases Research	000	6	3/9/2023	NON-COMPETING CONTINUATION	$571,418
2023	2023	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Cardiovascular Diseases Research	001	6	8/22/2023	SUPPLEMENT FOR EXPANSION	$571,309
														Subtotal = $1,142,727

Issue Date FY: 2022 ( Subtotal = $578,605 )
2022	2022	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Cardiovascular Diseases Research	001	5	3/20/2022	COMPETING CONTINUATION	$583,722
2022	2019	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Cardiovascular Diseases Research	000	4	11/20/2021	NON-COMPETING CONTINUATION	-$5,117
														Subtotal = $578,605

Issue Date FY: 2019 ( Subtotal = $373,750 )
2019	2019	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Cardiovascular Diseases Research	000	4	5/30/2019	NON-COMPETING CONTINUATION	$373,750
														Subtotal = $373,750

Issue Date FY: 2018 ( Subtotal = $373,750 )
2018	2018	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Cardiovascular Diseases Research	000	3	5/24/2018	NON-COMPETING CONTINUATION	$373,750
														Subtotal = $373,750

Issue Date FY: 2017 ( Subtotal = $373,750 )
2017	2017	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Cardiovascular Diseases Research	000	2	6/19/2017	NON-COMPETING CONTINUATION	$373,750
														Subtotal = $373,750

Issue Date FY: 2016 ( Subtotal = $373,750 )
2016	2016	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Cardiovascular Diseases Research	000	1	5/19/2016	NEW	$373,750
														Subtotal = $373,750

Grand Total All Awards = $4,290,597

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Cilia and Valvular Heart Disease

Award Number: R01HL131546

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2016

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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