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Discovering and Developing Recombinant Molecular Scavenging Agents for the Treatment of Carbon Monoxide Induced Cardiovascular Dysfunction

Award Number: K08HL136857
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 07/01/2018
PERIOD OF PERFORMANCE END DATE: 03/31/2024

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Discovering and Developing Recombinant Molecular Scavenging Agents for the Treatment of Carbon Monoxide Induced Cardiovascular Dysfunction - Project Summary/Abstract Dr. Jason Rose is resubmitting this application for a Mentored Research Career Development Award entitled “Discovering and Developing Recombinant Molecular Scavenging Agents for the Treatment of Carbon Monoxide (CO) Induced Cardiovascular Dysfunction”. Dr. Rose is a pulmonary and critical care physician, and now, Assistant Professor of Medicine at the University of Pittsburgh seeking additional training in molecular engineering, mitochondrial biology, animal models of disease, and drug discovery to further develop into an independent research investigator. His long-term goal is to lead large academic drug design, discovery and development programs. His short-term training goals, for this proposal, are to: (1) acquire proficiency in the assessment of cardiovascular pathophysiology in animal models of disease and develop the skillset to become a primary investigator in studying the role of mitochondrial dysfunction in human disease; (2) gain expertise in molecular engineering, targeted drug design and drug discovery assay development; and (3) develop the management skills to become an expert in the early-stage development of new therapeutics. Building on his recent graduation from the Tepper School of Business MBA program, he will supplement his training with didactic courses in molecular pharmacology, drug discovery and cardiovascular physiology. He has assembled experts in drug discovery, cardiovascular dynamics, and mitochondrial biology to form a cohesive mentor team and scientific advisory committee. The proposed work will be conducted within the Division of Pulmonary, Allergy, and Critical Care at the University of Pittsburgh, which has a strong history of training physician scientists and provides a superb infrastructure for his research and his path to academic independence. CO exposure is the leading cause of poisoning in the world and there is no antidote to CO. Current interventions have limited effectiveness: new therapies are needed. The central objective of this proposal is to further identify and develop an antidotal therapy for CO poisoning. Aim 1 will focus on establishing the mechanisms of CO- induced cardiovascular toxicity: investigating CO-induced mitochondrial inhibition and measuring hemodynamics in a severe CO poisoning mouse model. Aim 2 will test the efficacy and safety of recombinant neuroglobin to reverse the molecular and cardiac dysfunction caused by CO toxicity. Aim 3 will seek to identify novel heme containing molecules as CO scavengers, using a new manufacturing process and discovery assays. Although this proposal is ambitious, Dr. Rose has now completed his MBA degree during his intense clinical and research training demonstrating his ability to multitask in the academic environment. The combination of (1) formal training in cardiovascular physiology, innovation and molecular pharmacology; (2) novel research experience that includes disease modeling, drug development and discovery elements; (3) an experienced, diverse mentorship team and advisory committee; and (4) the strong institutional environment at the University of Pittsburgh will equip Dr. Rose for a career as an independent research investigator and academic drug discovery leader.


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: 2024 ( Subtotal = -$5,321 )
2024	2022	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cardiovascular Diseases Research	001	6	2/14/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$141,318
2024	2022	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cardiovascular Diseases Research	003	5	7/11/2024	NON-COMPETING CONTINUATION	-$12,664
2024	2022	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cardiovascular Diseases Research	000	5	2/13/2024	NON-COMPETING CONTINUATION	-$141,318
2024	2022	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cardiovascular Diseases Research	002	6	3/20/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2024	2022	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cardiovascular Diseases Research	006	6	8/1/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2024	2022	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cardiovascular Diseases Research	004	6	7/11/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$12,664
2024	2020	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cardiovascular Diseases Research	005	3	7/23/2024	SUPPLEMENT FOR EXPANSION	-$5,321
														Subtotal = -$5,321

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	5	9/20/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $161,892 )
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cardiovascular Diseases Research	001	5	6/29/2022	NON-COMPETING CONTINUATION	$161,892
2022	2020	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cardiovascular Diseases Research	000	3	3/11/2022	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $161,892

Issue Date FY: 2021 ( Subtotal = $161,892 )
2021	2021	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cardiovascular Diseases Research	000	4	7/1/2021	NON-COMPETING CONTINUATION	$161,892
														Subtotal = $161,892

Issue Date FY: 2020 ( Subtotal = $322,504 )
2020	2020	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Cardiovascular Diseases Research	000	3	7/8/2020	NON-COMPETING CONTINUATION	$161,796
2020	2020	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Cardiovascular Diseases Research	001	3	8/14/2020	SUPPLEMENT FOR EXPANSION	$160,708
2020	2020	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Cardiovascular Diseases Research	002	3	9/24/2020	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $322,504

Issue Date FY: 2019 ( Subtotal = $161,796 )
2019	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Cardiovascular Diseases Research	000	2	7/5/2019	NON-COMPETING CONTINUATION	$161,796
														Subtotal = $161,796

Issue Date FY: 2018 ( Subtotal = $161,796 )
2018	2018	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Cardiovascular Diseases Research	000	1	5/5/2018	NEW	$161,796
														Subtotal = $161,796

Grand Total All Awards = $964,559

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Discovering and Developing Recombinant Molecular Scavenging Agents for the Treatment of Carbon Monoxide Induced Cardiovascular Dysfunction

Award Number: K08HL136857

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 07/01/2018

PERIOD OF PERFORMANCE END DATE: 03/31/2024

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