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Integrating imaging and computation to characterize neural crest cells in the myocardial development and regeneration

Award Number: R00HL148493
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Integrating imaging and computation to characterize neural crest cells in the myocardial development and regeneration - Project Summary / Abstract Integrating imaging and computation to characterize neural crest cells in the myocardial development and regeneration Cardiac neural crest cells are a population of highly migratory cells emerging from the neural tube, migrating through the pharyngeal arches and integrating into the developing heart. Recent advances demonstrate that a new sub-population of neural crest cells has the capacity to integrate into the cardiac chamber and differentiate into cardiomyocytes in both zebrafish and mice. Notch signaling regulates cardiomyocyte proliferation and differentiation during ventricular chamber development. Despite the knowledge gained in the past decades, the contribution of neural crest-derived cardiomyocytes to contractile function and the role of these cardiomyocytes in Notch signaling-mediated ventricular remodeling remain elusive. The small heart size in zebrafish embryos and neonatal mice also hinders precise cardiac structural and functional assessment. For these reasons, I seek to integrate our advanced imaging (sub-voxel resolution light-sheet fluorescence microscopy, SV-LSFM) with computation (displacement analysis of myocardial mechanical deformation, DIAMOND) to characterize the structural and functional contributions of the neural crest-derived cardiomyocytes to the myocardial development and regeneration with high spatiotemporal resolution. Under the joint mentorship from Professor Tzung Hsiai (Mechanotransduction, UCLA), Professor Jau-Nian Chen (Developmental biology, UCLA) and Professor Debiao Li (MR imaging, Cedars-Sinai Medical Center), I will continue to collaborate with Professor Atsushi Nakano (Developmental biology, UCLA) and Dr. Adam Langenbacher (Developmental biology, UCLA), and consult with Professor Joseph Wu (Cardiac stem cells, Stanford), Professor Sandra Rugonyi (Oregon Health & Science University), Professor Linda Demer (Vascular biology, UCLA) to test our hypothesis. We hypothesize that neural crest cells contribute to the ventricular myocardium and neural crest-derived cardiomyocytes are essential for the contractile function and ventricular repair. To test this hypothesis, we will have three aims. In Aim 1, we will elucidate the 4-D migration path of cardiac neural crest cell via SV-LSFM. In Aim 2, we will demonstrate 4-D structure and function following cardiac neural crest cell contribution to the ventricular myocardium via DIAMOND. In Aim 3, I will independently quantify the ventricular repair following the ablation of neural crest-derived cardiomyocytes in zebrafish and mouse models with my collaborators. In this context, we believe that the integration of genetic models with advanced imaging and computation will provide new mechanical and developmental insights into the contribution of neural crest cells to contractile function and ventricular repair under the regulation of Notch signaling pathway.


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 = -$27,671 )
2025	2022	UNIVERSITY OF TEXAS AT DALLAS	800 WEST CAMPBELL RD.	RICHARDSON	TX	75080	DALLAS	USA	Cardiovascular Diseases Research	000	4	3/24/2025	NON-COMPETING CONTINUATION	-$27,671
														Subtotal = -$27,671

Issue Date FY: 2022 ( Subtotal = $238,902 )
2022	2022	UNIVERSITY OF TEXAS AT DALLAS	800 W CAMPBELL RD	RICHARDSON	TX	75080	DALLAS	USA	Cardiovascular Diseases Research	000	4	9/2/2022	NON-COMPETING CONTINUATION	$238,902
														Subtotal = $238,902

Issue Date FY: 2021 ( Subtotal = $270,390 )
2021	2021	UNIVERSITY OF TEXAS AT DALLAS	800 W CAMPBELL RD	RICHARDSON	TX	75080	DALLAS	USA	Cardiovascular Diseases Research	001	3	8/18/2021	NON-COMPETING CONTINUATION	$244,750
2021	2020	UNIVERSITY OF TEXAS AT DALLAS	800 W CAMPBELL RD	RICHARDSON	TX	75080	DALLAS	USA	Cardiovascular Diseases Research	000	2	3/19/2021	EXTENSION WITH OR WITHOUT FUNDS	$25,640
														Subtotal = $270,390

Issue Date FY: 2020 ( Subtotal = $246,552 )
2020	2020	UNIVERSITY OF TEXAS AT DALLAS	800 W CAMPBELL RD	RICHARDSON	TX	75080	DALLAS	USA	Cardiovascular Diseases Research	000	2	9/3/2020	EXTENSION WITH OR WITHOUT FUNDS	$246,552
														Subtotal = $246,552

Grand Total All Awards = $728,173

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Integrating imaging and computation to characterize neural crest cells in the myocardial development and regeneration

Award Number: R00HL148493

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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