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Exosomes as mediators of cardiac injury and repair

Award Number: P01HL134608
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2017
PERIOD OF PERFORMANCE END DATE: 06/30/2029

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Exosomes as mediators of cardiac injury and repair - Summary For a complex organ like heart, well-organized interactions between different cell types are essential for its effective functioning. Cell-cell communication between these myriad cell types therefore appears to be key component of cardiac function and a better understanding of how different cells within injured myocardium communicate with each other during homeostasis and injury and elucidation of molecular events downstream of such communications is critical to identify new therapeutic targets for cardiac healing after injury. Increasing evidence suggest that extracellular vesicles (EVs) including exosomes are major paracrine conduits of cardiac cell-cell communication in homeostasis and disease conditions. However, a comprehensive understanding of how cardiac injury alters exosome-mediated cell-cell communications both locally within myocardium and at long distance organs such as bone marrow and adipose tissue and whether these exosome-mediated alterations in cell-cell communications influence overall cardiac structure and function and repair is not well understood. The overarching hypothesis of this renewal application is that cardiac injury alters exosome- mediated specific cell-cell communication both locally within the injured myocardium and distally with other organs and these intra-cellular and inter-organ communications influence overall myocardial responses to injury and repair processes. To test our hypothesis, we have assembled a team of highly accomplished scientists who have the potential to markedly advance the science and application of exosome biology for ischemic tissue repair. In particular, the design of this program, highlighted in inter-related yet unique individual projects, intends to capitalize on our existing synergy and assets. We will utilize the advantage of strategically designed scientific cores that will support each project. We will apply various techniques of molecular, cellular, and biochemical approaches in cell models and mice models of myocardial injury and repair. Project 1 (Kishore) examines the role of stressed cardiomyocyte-derived exosomes, particularly cardiomyocyte specific microRNAs, on post-injury endothelial and endothelial progenitor cell function and angiogenesis. Project 2 (Walter Koch) focuses upon the involvement of cardiac exosomes containing G-protein coupled receptor kinase 2 on adipocytes and cardiac cell function. Project 3 (Tilley) examines the role of beta-2 adrenergic receptor on myeloid cell exosomes and cardiac functions. All three projects involve in-depth molecular, cellular, and physiological studies comprising of mouse models of myocardial injury. Establishing the role of exosomes in post-injury cell to cell communications may identify new mechanisms and therapeutic targets for post-injury myocardial repair. The goal of this program will be to delineate exosome mediated signaling mechanisms and determine how they can be utilized to restore and enhance endogenous cellular repair processes that heal the damaged heart.


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 = $2,379,218 )
2025	2025	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1805 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Cardiovascular Diseases Research	002	7	7/31/2025	NON-COMPETING CONTINUATION	$2,379,218
2025	2024	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1805 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Cardiovascular Diseases Research	001	6	3/11/2025	COMPETING CONTINUATION	$144,396
2025	2021	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1805 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	5	3/11/2025	NON-COMPETING CONTINUATION	-$144,396
														Subtotal = $2,379,218

Issue Date FY: 2024 ( Subtotal = $2,393,843 )
2024	2024	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1805 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Cardiovascular Diseases Research	001	6	5/30/2024	COMPETING CONTINUATION	$2,393,843
2024	2021	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1805 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	5	5/28/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,393,843

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1801 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	5	7/6/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1801 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	5	7/16/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $2,249,182 )
2021	2021	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1801 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	5	7/14/2021	NON-COMPETING CONTINUATION	$2,249,182
														Subtotal = $2,249,182

Issue Date FY: 2020 ( Subtotal = $2,288,095 )
2020	2020	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1801 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	4	7/8/2020	NON-COMPETING CONTINUATION	$2,288,095
														Subtotal = $2,288,095

Issue Date FY: 2019 ( Subtotal = $2,325,872 )
2019	2019	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1801 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	3	7/18/2019	NON-COMPETING CONTINUATION	$2,325,872
														Subtotal = $2,325,872

Issue Date FY: 2018 ( Subtotal = $2,362,544 )
2018	2018	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1801 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	2	8/22/2018	NON-COMPETING CONTINUATION	$2,362,544
														Subtotal = $2,362,544

Issue Date FY: 2017 ( Subtotal = $2,363,250 )
2017	2017	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1801 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	1	8/25/2017	NEW	$2,363,250
														Subtotal = $2,363,250

Grand Total All Awards = $16,362,004

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Exosomes as mediators of cardiac injury and repair

Award Number: P01HL134608

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2017

PERIOD OF PERFORMANCE END DATE: 06/30/2029

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