Wednesday, April 2, 2025 4/2/2025

Defining cellular mechanisms of chronic graft failure in transplanted hearts with single cell multi-omics

Award Number: R01HL160552
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By:

View Award Description

Defining cellular mechanisms of chronic graft failure in transplanted hearts with single cell multi-omics - Project Summary/Abstract Heart transplantation is a definitive treatment option for patients with end-stage heart failure. While short-term survival has made substantial improvements, long-term outcomes are limited by chronic graft failure. Cardiac allograft hypertrophy (CAH) is a clinical phenomenon referring to the gradual increase of left ventricular mass and wall thickness of cardiac grafts. CAH onset can occur as early as 2 months after transplantation, which often lead to progressive changes in cellular environment including cardiomyocytes hypertrophy and fibrosis and accumulate to graft failure in long term. The complete landscape of cellular system in transplant patients represents a major gap in knowledge. Single cell RNA sequencing (scRNA-seq) has emerged as powerful tool to analyze diverse cell types and cell states as well as pseudo-time topologies of single cells in complex organs, which however lacks the power to infer cell lineages that is important for identify the origins of pathogenic cells. In this project, we will develop a novel single cell multi-omics sequencing technology and several computational tools, which will enable simultaneous detection of cell lineage markers (i.e. DNAs) and cell fate markers (i.e. RNAs) from same cells. We will also distinguish donor and host identities for all cells to study their distinct roles in CAH that are largely unknown. We hypothesized that CAH is initiated by specific immune cell subtypes and driven by endothelial to mesenchymal transition that is fueled by enlarged cardiomyocytes. In aim 1, we will develop novel technology to define a unifying cell lineage and cell fate roadmap for cardiac cells. Aim 2 will dissect temporal changes of cellular components in transplanted hearts during CAH early onset. Aim 3 is to trace cell lineages during CAH progression with time-series single cell multi-omics. Successful completion of this project will lead to the identification of donor and host originated cell populations as novel therapeutic targets to extend the life of transplant 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 = $374,875 )
2025	2025	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cardiovascular Diseases Research	000	4	3/28/2025	NON-COMPETING CONTINUATION	$374,875
														Subtotal = $374,875

Issue Date FY: 2024 ( Subtotal = $408,197 )
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cardiovascular Diseases Research	000	3	3/22/2024	NON-COMPETING CONTINUATION	$374,875
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cardiovascular Diseases Research	001	3	6/22/2024	NON-COMPETING CONTINUATION	$33,322
														Subtotal = $408,197

Issue Date FY: 2023 ( Subtotal = $416,528 )
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cardiovascular Diseases Research	000	2	3/20/2023	NON-COMPETING CONTINUATION	$416,528
														Subtotal = $416,528

Issue Date FY: 2022 ( Subtotal = $434,154 )
2022	2022	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cardiovascular Diseases Research	000	1	4/19/2022	NEW	$434,154
														Subtotal = $434,154

Grand Total All Awards = $1,633,754

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Defining cellular mechanisms of chronic graft failure in transplanted hearts with single cell multi-omics

Award Number: R01HL160552

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer