Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Characterization of hapln1a positive cells during zebrafish heart regeneration

Award Number: R01HL142762
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2018
PERIOD OF PERFORMANCE END DATE: 03/31/2028

Group Awards By:

View Award Description

Characterization of hapln1a positive cells during zebrafish heart regeneration - Project Summary Humans, like all mammals, possess a limited natural ability to efficiently replace lost myocardium with new contractile tissue. This deficiency contributes to heart failure, the leading cause of morbidity and mortality in the United States. By contrast, teleost fish robustly restore lost cardiac tissues after heart damage. Heart regeneration in its natural context builds muscle by the proliferation of existing cardiomyocytes (CMs), facilitated by the influences of non-muscle cells like the epicardium, which is a mesothelial layer that envelops the outer surface of the heart and has important contributions to cardiac repair. However, the epicardium itself is a heterogeneous tissue and which subpopulations offer benefits to regeneration events is far from clear. Our study reveals that a particular subset of epicardial cells with hapln1a expression has the strongest association with regeneration. hapln1a+ epicardial cells first emerge in the ventricle base at the early juvenile stage, when they associate with and sponsor regions of active CM expansion, events which direct maturation of the ventricular wall during morphogenesis and restore lost myocardium during adult heart regeneration. Our preliminary work further indicates that hapln1a+ cells pre-lead and guide coronary extensions during heart morphogenesis and regeneration. Our single-cell RNA sequencing (scRNA-seq) analyses of hapln1a+ cells from juvenile, adult uninjured, and regenerating hearts indicates that these cells are still heterogenous with different functional clusters. We speculate that hapln1a+ cells can be genetically separated into subsets that are specifically responsible for CM proliferation and coronary guidance, respectively. Our goal in this proposal is to identify specific hapln1a+ cell clusters to pursue cell populations for therapeutic strategies. Our overall hypothesis is that tcf21+ cell derived hapln1a+ cells have different clusters controlling myocardial expansion and coronary guidance, a process in which has1 and serpine1 play critical roles in regulating extracellular matrix. To test this hypothesis, we have created a panel of new zebrafish transgenic lines and mutants. We will define hapln1a+ cell dynamism and related regulators, identify hapln1a+ cell clusters for CM proliferation and coronary guidance, and the underlying molecular players. Our work will generate paradigm-shifting discoveries in cardiovascular biology. These studies will reveal the impact of epicardial subsets on heart regeneration and identify key cellular and molecular players in myocardial regeneration and coronary revascularization. These findings will potentially lead to new therapeutic strategies like augmenting hapln1a+ cells and subpopulations to enhance the limited regeneration displayed by humans after myocardial infarction.


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 = $450,374 )
2026	2026	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Cardiovascular Diseases Research	000	6	4/9/2026	NON-COMPETING CONTINUATION	$450,374
														Subtotal = $450,374

Issue Date FY: 2025 ( Subtotal = $469,948 )
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Cardiovascular Diseases Research	001	5	6/30/2025	NON-COMPETING CONTINUATION	$46,995
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Cardiovascular Diseases Research	000	5	4/7/2025	NON-COMPETING CONTINUATION	$422,953
														Subtotal = $469,948

Issue Date FY: 2024 ( Subtotal = $477,326 )
2024	2024	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Cardiovascular Diseases Research	001	4	3/29/2024	COMPETING CONTINUATION	$432,020
2024	2024	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Cardiovascular Diseases Research	002	4	6/10/2024	COMPETING CONTINUATION	$48,003
2024	2021	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Cardiovascular Diseases Research	000	3	2/28/2024	NON-COMPETING CONTINUATION	-$2,697
														Subtotal = $477,326

Issue Date FY: 2021 ( Subtotal = $390,000 )
2021	2021	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Cardiovascular Diseases Research	000	3	8/22/2021	NON-COMPETING CONTINUATION	$390,000
														Subtotal = $390,000

Issue Date FY: 2020 ( Subtotal = $390,533 )
2020	2020	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Cardiovascular Diseases Research	001	2	8/25/2020	NON-COMPETING CONTINUATION	$390,000
2020	2019	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Cardiovascular Diseases Research	000	1	5/15/2020	NEW	$533
														Subtotal = $390,533

Issue Date FY: 2019 ( Subtotal = $390,000 )
2019	2019	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Cardiovascular Diseases Research	000	1	4/14/2019	NEW	$390,000
														Subtotal = $390,000

Grand Total All Awards = $2,568,181

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Characterization of hapln1a positive cells during zebrafish heart regeneration

Award Number: R01HL142762

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/15/2018

PERIOD OF PERFORMANCE END DATE: 03/31/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer