Monday, February 16, 2026 2/16/2026

Single-cell Multi-omic Profiling of Drug Responses Using Pooled iPSC-CM Differentiation

Award Number: R01HL145676
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2019
PERIOD OF PERFORMANCE END DATE: 04/30/2027

Group Awards By:

View Award Description

Single-cell Multi-omic Profiling of Drug Responses Using Pooled iPSC-CM Differentiation - PROJECT SUMMARY Cardiovascular complications of cancer therapy significantly contribute to the global burden of cardiovascular diseases. Although remarkable progress has been made in understanding the genetic basis of doxorubicin- induced cardiotoxicity (DIC), we cannot predict which patients will be affected by DIC or protect patients at risk for suffering from DIC adequately. Here, we will use a novel multiplexing methodology of creating a cell village by pooling multiple patients' induced pluripotent stem cell (iPSC) lines in a dish to map the genetic basis of inter- individual differences in response to doxorubicin. In Aim 1, we will co-culture 100 iPSC lines in 10 distinct cell villages, where each cell village contains ten independent patient-specific iPSC lines. Next, we will differentiate each cell village into iPSC-derived cardiomyocytes (iPSC-CMs). Finally, we will perform a single-cell multi- omics sequencing analysis of the cell villages to understand the impact of genetic variability on cardiomyocyte gene regulation and functions at baseline. In Aim 2, we will employ a single-cell multi-omic approach to uncover and validate the role of response eQTL in DIC prediction. We will treat iPSC-CMs in each cell village with doxorubicin at various doses. Next, we will perform single-cell multi-omics profiling to model the contribution of genetics to variability in responses to doxorubicin treatment. In Aim 3, we will employ 3D engineered heart tissues (EHTs) and CRISPR/cas9 genome-editing to comprehensively study the functional role of two candidate doxorubicin response genes. All in all, the proposed experiments will serve as a proof-of- principle in using the cell village model as a high throughput personalized drug screening platform.


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 = $599,975 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	001	7	5/23/2025	NON-COMPETING CONTINUATION	$599,975
2025	2022	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	4	1/30/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $599,975

Issue Date FY: 2024 ( Subtotal = $597,054 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	6	7/15/2024	NON-COMPETING CONTINUATION	$597,054
														Subtotal = $597,054

Issue Date FY: 2023 ( Subtotal = $618,158 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	001	5	4/28/2023	COMPETING CONTINUATION	-$2,664
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	5	3/29/2023	COMPETING CONTINUATION	$620,822
														Subtotal = $618,158

Issue Date FY: 2022 ( Subtotal = $675,692 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	4	6/23/2022	NON-COMPETING CONTINUATION	$675,692
														Subtotal = $675,692

Issue Date FY: 2021 ( Subtotal = $684,695 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	3	5/6/2021	NON-COMPETING CONTINUATION	$684,695
														Subtotal = $684,695

Issue Date FY: 2020 ( Subtotal = $692,649 )
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	2	5/5/2020	NON-COMPETING CONTINUATION	$692,649
														Subtotal = $692,649

Issue Date FY: 2019 ( Subtotal = $701,120 )
2019	2019	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	1	4/24/2019	NEW	$701,120
2019	2019	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	001	1	9/14/2019	NEW	$0
														Subtotal = $701,120

Grand Total All Awards = $4,569,343

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Single-cell Multi-omic Profiling of Drug Responses Using Pooled iPSC-CM Differentiation

Award Number: R01HL145676

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2019

PERIOD OF PERFORMANCE END DATE: 04/30/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer