Tuesday, July 1, 2025 7/1/2025

Human iPSC Model to Elucidate Metabolic Interplay in Diabetic Cardimyopathy

Award Number: R01HL146690
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2019
PERIOD OF PERFORMANCE END DATE: 04/30/2027

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Human iPSC Model to Elucidate Metabolic Interplay in Diabetic Cardimyopathy - Project Summary Type 2 diabetes (T2D) is a leading cause of death nationwide with 65% of mortality due to cardiovascular disease. The term “diabetic cardiomyopathy (T2DCM)” refers to a condition with adverse myocardial structural changes, in the absence of hypertension and vascular pathology. Although T2D and CVD are tightly intertwined, we lack a deeper understanding of T2DCM at the molecular and cellular levels. In recent years, sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as a promising therapeutic for T2DCM, but the precise protective mechanisms in cardiomyocytes, fibroblasts, and endothelial cells which construct the cardiac microenvironment remain incompletely understood. In this multi-PI R01 renewal, our team will elucidate the mechanisms of metabolic interplay within and between cardiovascular cells which confer cardiac protection by SGLT2 inhibition. We will harness induced pluripotent stem cell (iPSC) technology to generate diabetic models of cardiovascular cell types for cellular and metabolic phenotyping of SGLT2 inhibition in vitro (Aim 1). We will construct iPSC-derived engineered heart tissues for functional phenotyping and proteomic determination of the SGLT2 inhibitor protein interactome (Aim 2). Afterward, we will validate cardioprotective mechanisms in a diabetic mouse model at single-cell resolution (Aim 3). In summary, understanding the exact role and mechanism of SGLT2 inhibition in T2DCM may contribute to finding new therapeutic modalities for the treatment of metabolic heart diseases.


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 = $678,661 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	003	7	6/19/2025	NON-COMPETING CONTINUATION	$678,661
2025	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	002	5	3/14/2025	COMPETING CONTINUATION	$1,053,421
2025	2022	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	001	4	3/14/2025	NON-COMPETING CONTINUATION	-$735,262
2025	2021	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	3	3/14/2025	NON-COMPETING CONTINUATION	-$318,159
														Subtotal = $678,661

Issue Date FY: 2024 ( Subtotal = $672,653 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	001	6	6/25/2024	NON-COMPETING CONTINUATION	$54,910
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	6	4/19/2024	NON-COMPETING CONTINUATION	$617,743
														Subtotal = $672,653

Issue Date FY: 2023 ( Subtotal = $696,320 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	002	5	7/20/2023	COMPETING CONTINUATION	$0
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	001	5	7/10/2023	COMPETING CONTINUATION	$696,320
2023	2022	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	4	7/9/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $696,320

Issue Date FY: 2022 ( Subtotal = $691,027 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	001	4	4/3/2022	NON-COMPETING CONTINUATION	$688,280
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	002	4	6/29/2022	NON-COMPETING CONTINUATION	$46,982
2022	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	3	4/2/2022	NON-COMPETING CONTINUATION	-$44,235
														Subtotal = $691,027

Issue Date FY: 2021 ( Subtotal = $830,932 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	3	3/12/2021	NON-COMPETING CONTINUATION	$830,932
														Subtotal = $830,932

Issue Date FY: 2020 ( Subtotal = $804,126 )
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	001	2	9/23/2020	SUPPLEMENT FOR EXPANSION	$53,214
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	2	3/5/2020	NON-COMPETING CONTINUATION	$750,912
														Subtotal = $804,126

Issue Date FY: 2019 ( Subtotal = $758,244 )
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
2019	2019	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Cardiovascular Diseases Research	000	1	3/14/2019	NEW	$758,244
														Subtotal = $758,244

Grand Total All Awards = $5,131,963

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Human iPSC Model to Elucidate Metabolic Interplay in Diabetic Cardimyopathy

Award Number: R01HL146690

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2019

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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