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Computational and Experimental Investigations of Deformation-Driven Molecular Pathways in Single Right Ventricle Congenital Heart Disease

Award Number: K25HL186164
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 07/03/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2031

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Computational and Experimental Investigations of Deformation-Driven Molecular Pathways in Single Right Ventricle Congenital Heart Disease - PROJECT SUMMARY/ABSTRACT Approximately 1-in-3 children with single right ventricle congenital heart disease develop tricuspid valve regurgitation within 20 years of Fontan completion. Tricuspid valve regurgitation is associated with a 2.4-times increased risk of circulatory failure. There are currently no effective medications to treat this regurgitation, so patients with severe regurgitation undergo additional surgery to restore valve function. Unfortunately, many valve repairs fail within 5 years and patients develop recurrent tricuspid valve regurgitation. It is currently unknown why this occurs, but it is possible that cell-driven leaflet growth and remodeling plays an important role. Prior studies have demonstrated a clear correlation between deformation-driven changes to cellular morphology (specifically the nuclear aspect ratio) and growth and remodeling of the extracellular matrix. However, our inability to estimate in-vivo cellular deformations and lack of mechanistic insight connecting cellular deformations to growth and remodeling endpoints limits our capacity to address tricuspid valve regurgitation for this vulnerable population. Dr. Laurence is a young investigator with a rich background in computational biomechanics who is uniquely poised at the Children’s Hospital of Philadelphia to address these shortcomings. Dr. Laurence lacks training in cellular and molecular biology to define the mechanistic relationship between cellular deformations and tissue growth and remodeling. The objective of this project is to provide the requisite career development in cellular and molecular biology so that Dr. Laurence can achieve two specific research goals: (1) define how in-vivo cell deformations differ for patients with single right ventricle congenital heart disease compared to healthy biventricular physiology and (2) delineate the mechanisms that translate cellular deformations to tissue growth and remodeling. Successful completion of these goals will significantly advance the current understanding of how tricuspid valve regurgitation develops or recurs for children with single right ventricle congenital heart disease. Furthermore, the proposed career development activities will substantially enrich Dr. Laurence’s research portfolio and allow him to incorporate realistic biological mechanisms into computational workflows. This will allow Dr. Laurence to pursue his long-term research goal of improving outcomes for children with single right ventricle congenital heart disease and competitively pursue independent research funding.


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 = $115,584 )
2026	2026	THE CHILDREN'S HOSPITAL OF PHILADELPHIA	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	1	7/8/2026	NEW	$115,584
														Subtotal = $115,584

Grand Total All Awards = $115,584

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Computational and Experimental Investigations of Deformation-Driven Molecular Pathways in Single Right Ventricle Congenital Heart Disease

Award Number: K25HL186164

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 07/03/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2031

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