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Administrative supplement - Childcare

Award Number: F32HL156428
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 08/01/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2022

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Administrative supplement - Childcare - Abstract Sudden cardiac arrest is highly prevalent and results in overwhelming mortality. Unfortunately, there are no pharmacologic therapies that have been shown to reliably increase survival after sudden cardiac arrest. Survivors of sudden cardiac arrest typically have systemic organ damage requiring intensive care in the hospital. The majority of these patients have reduced cardiac function and one quarter of these patients die from cardiogenic shock. One of the mechanisms driving cardiac dysfunction after cardiac arrest and resuscitation is the production of reactive oxygen species (ROS) in the heart, particularly in the mitochondria. Mitochondrial ROS is known to cause damage to nearby mitochondrial DNA (mtDNA), which are crucial for maintaining mitochondrial function. Preliminary work in our lab has shown that methods aimed at preserving mtDNA integrity, including mitochondrial targeted antioxidant therapy and overexpression of mitochondrial transcription factor A (TFAM), are protective to cardiac function in a mouse model of sudden cardiac arrest. TFAM is a nuclear gene that regulates mtDNA expression, packaging, and copy number and is known to be protective in a number of heart disease models. My overarching hypothesis is that ischemia-reperfusion injury from cardiac arrest results in mtDNA damage secondary to mitochondrial ROS production, leading to impaired electron transport chain protein regulation and cardiac dysfunction. To explore this hypothesis, I will pursue two specific aims. In Aim 1, I will test the link between cardiac arrest, ROS production, mtDNA damage, and cardiac function using mitochondrial antioxidants in an in vivo mouse model of cardiac arrest as well as a cellular model of ischemia-reperfusion. In Aim 2, I will test whether the levels of TFAM specifically in the cardiomyocytes modulate the development of cardiomyopathy and survival in the cardiac arrest model. Together, these aims will demonstrate that mtDNA damage following cardiac arrest is mediated by mitochondrial ROS and contributes to post-arrest cardiomyopathy. Further, they will show that these changes can be prevented by mitochondrial ROS scavenging and manipulation of TFAM, which may be targets for novel therapeutic interventions in cardiac arrest 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: 2023 ( Subtotal = $0 )
2023	2022	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cardiovascular Diseases Research	000	1	5/15/2023	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = -$2,535 )
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cardiovascular Diseases Research	002	1	8/31/2022	SUPPLEMENT FOR EXPANSION	-$151
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cardiovascular Diseases Research	000	1	3/15/2022	SUPPLEMENT FOR EXPANSION	$2,500
2022	2021	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cardiovascular Diseases Research	001	1	8/31/2022	NEW	-$4,884
														Subtotal = -$2,535

Issue Date FY: 2021 ( Subtotal = $70,458 )
2021	2021	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Cardiovascular Diseases Research	000	1	2/1/2021	NEW	$69,306
2021	2021	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cardiovascular Diseases Research	003	1	4/7/2021	NEW	$0
2021	2021	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cardiovascular Diseases Research	001	1	4/7/2021	NEW	$1,152
2021	2021	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cardiovascular Diseases Research	002	1	4/7/2021	NEW	$0
														Subtotal = $70,458

Grand Total All Awards = $67,923

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Administrative supplement - Childcare

Award Number: F32HL156428

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 08/01/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2022

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