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Human Induced Pluripotent Stem Cells for Cardiovascular Disease Modeling

Award Number: R01HL113006
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2012
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Human Induced Pluripotent Stem Cells for Cardiovascular Disease Modeling - PROJECT SUMMARY While dilated cardiomyopathy (DCM) is one of the most common hereditary heart diseases, we currently lack effective and targeted treatments. Cardiac fibrosis is an important hallmark of DCM and the presence of excessive fibrotic tissues can severely hamper heart function. However, limited information exists on how DCM mutations can induce cardiac fibrosis in familial DCM patients. This study aims to address this significant knowledge gap using patient-specific human induced pluripotent stem cells (iPSCs) generated from common DCM patients. In Aim 1, we will differentiate iPSCs into cardiac fibroblasts (iPSC-CFs) and cardiomyocytes (iPSC-CMs) to study how cardiomyocyte-specific and non-cardiomyocyte-specific mutations can activate cardiac fibroblasts. In Aim 2, we will examine whether iPSC-CFs induce cardiac dysfunction through secretory factors and/or direct interaction with cardiomyocytes using a 3D engineered heart tissues (EHT) platform. In Aim 3, we will identify gene/mutation-specific druggable targets using state-of-the-art CRISPR/dCas9i (inhibitory) and CRISPR/dCas9a (activating) technologies, and validate these targets in an established DCM mouse model. By completing this study, we expect to identify fibrosis-inducing DCM mutations, understand how they activate cardiac fibroblasts, and potentially discover novel druggable mechanism to manage DCM. Collectively, this multi- PI R01 study has tremendous translational value to aid future precision cardiovascular medicine.


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 = $607,740 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	13	4/30/2025	NON-COMPETING CONTINUATION	$607,740
														Subtotal = $607,740

Issue Date FY: 2024 ( Subtotal = $668,711 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	001	12	5/20/2024	NON-COMPETING CONTINUATION	$668,711
2024	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	11	12/18/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $668,711

Issue Date FY: 2023 ( Subtotal = $691,803 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	11	2/24/2023	NON-COMPETING CONTINUATION	$691,803
														Subtotal = $691,803

Issue Date FY: 2022 ( Subtotal = $701,008 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	003	10	6/28/2022	COMPETING CONTINUATION	$0
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	001	10	3/6/2022	COMPETING CONTINUATION	$701,247
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	002	10	5/6/2022	COMPETING CONTINUATION	$0
2022	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	9	2/1/2022	NON-COMPETING CONTINUATION	-$239
														Subtotal = $701,008

Issue Date FY: 2020 ( Subtotal = $481,020 )
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	9	6/17/2020	NON-COMPETING CONTINUATION	$481,020
														Subtotal = $481,020

Issue Date FY: 2019 ( Subtotal = $578,512 )
2019	2019	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	8	7/24/2019	NON-COMPETING CONTINUATION	$578,512
														Subtotal = $578,512

Issue Date FY: 2018 ( Subtotal = $605,838 )
2018	2018	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	001	7	7/17/2018	NON-COMPETING CONTINUATION	$597,085
2018	2018	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	6	7/13/2018	SUPPLEMENT FOR EXPANSION	$8,753
														Subtotal = $605,838

Issue Date FY: 2017 ( Subtotal = $502,306 )
2017	2017	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	001	6	7/19/2017	COMPETING CONTINUATION	$502,400
2017	2016	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	5	5/12/2017	EXTENSION WITH OR WITHOUT FUNDS	-$94
														Subtotal = $502,306

Issue Date FY: 2016 ( Subtotal = $393,018 )
2016	2016	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	5	2/26/2016	EXTENSION WITH OR WITHOUT FUNDS	$393,018
														Subtotal = $393,018

Issue Date FY: 2015 ( Subtotal = $387,104 )
2015	2015	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	4	1/26/2015	NON-COMPETING CONTINUATION	$387,104
														Subtotal = $387,104

Issue Date FY: 2014 ( Subtotal = $385,120 )
2014	2014	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	3	2/21/2014	NON-COMPETING CONTINUATION	$353,681
2014	2014	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	001	3	3/4/2014	NON-COMPETING CONTINUATION	$31,439
														Subtotal = $385,120

Issue Date FY: 2013 ( Subtotal = $374,100 )
2013	2013	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	001	2	6/25/2013	NON-COMPETING CONTINUATION	$20,435
2013	2013	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	2	1/31/2013	NON-COMPETING CONTINUATION	$353,665
														Subtotal = $374,100

Issue Date FY: 2012 ( Subtotal = $392,944 )
2012	2012	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	1	4/27/2012	NEW	$392,944
														Subtotal = $392,944

Grand Total All Awards = $6,769,224

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Human Induced Pluripotent Stem Cells for Cardiovascular Disease Modeling

Award Number: R01HL113006

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2012

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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