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Chemistry and Biology of ADP-Ribosylation-Dependent Signaling

Award Number: R35GM137901
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2020
PERIOD OF PERFORMANCE END DATE: 03/31/2031

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Chemistry and Biology of ADP-Ribosylation-Dependent Signaling - Abstract Protein ADP-ribosylation is a complex and highly dynamic process controlled by distinct writer, reader and eraser proteins. As major intracellular writers, poly-ADP-ribose polymerases (PARPs) are responsible for catalyzing this key type of post-translational modification by using nicotinamide adenine dinucleotide (NAD+) as a co-substrate and play pivotal roles in regulating a significant number of physiological and pathophysiological events. By specifically recognizing ADP-ribosylated proteins, reader proteins can trigger downstream signaling cascades or effector functions in direct or indirect manners. Eraser proteins can modulate ADP-ribosylation- mediated signaling activities through rapid removals of covalently attached ADP-ribose unit(s). The writers, readers, and erasers constitute ADP-ribosylation-based interaction networks that are not only extensively involved in human health but also implicated in pathogenesis of numerous diseases. Despite technological advancement, little information is known regarding the ADP-ribosylation-dependent interactome under physiological conditions for individual PARP writers of interest. Moreover, few chemical probes with sufficient specificity are available for unambiguously studying disease-relevant PARP isoforms. The goals of this MIRA project are to develop novel chemical tools to address these major challenges and functionally and mechanistically dissect ADP-ribosylation-regulated networks across varied cellular contexts. Successful completion of this work will result in a set of innovative chemical probes for in-depth studies of ADP-ribosylation- mediated signaling and advance our understanding of functions and roles of protein ADP-ribosylation in physiology and pathophysiology, leading to potential major breakthroughs in the development of new diagnostics and therapeutics targeting ADP-ribosylation-associated activities and pathways for many human 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: 2026 ( Subtotal = $456,500 )
2026	2026	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Biomedical Research and Research Training	001	6	3/13/2026	COMPETING CONTINUATION	$456,500
2026	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Biomedical Research and Research Training	000	5	3/5/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $456,500

Issue Date FY: 2024 ( Subtotal = $378,183 )
2024	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Biomedical Research and Research Training	000	5	6/24/2024	NON-COMPETING CONTINUATION	$378,183
														Subtotal = $378,183

Issue Date FY: 2023 ( Subtotal = $389,784 )
2023	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Biomedical Research and Research Training	001	4	6/27/2023	SUPPLEMENT FOR EXPANSION	$11,601
2023	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Biomedical Research and Research Training	000	4	6/26/2023	NON-COMPETING CONTINUATION	$378,183
														Subtotal = $389,784

Issue Date FY: 2022 ( Subtotal = $447,787 )
2022	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Biomedical Research and Research Training	000	3	6/16/2022	NON-COMPETING CONTINUATION	$378,183
2022	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Biomedical Research and Research Training	001	3	6/17/2022	SUPPLEMENT FOR EXPANSION	$69,604
														Subtotal = $447,787

Issue Date FY: 2021 ( Subtotal = $436,185 )
2021	2021	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Biomedical Research and Research Training	000	2	6/10/2021	NON-COMPETING CONTINUATION	$378,183
2021	2021	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Biomedical Research and Research Training	001	2	8/23/2021	SUPPLEMENT FOR EXPANSION	$58,002
														Subtotal = $436,185

Issue Date FY: 2020 ( Subtotal = $394,433 )
2020	2020	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Biomedical Research and Research Training	000	1	6/30/2020	NEW	$394,433
														Subtotal = $394,433

Grand Total All Awards = $2,502,872

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Chemistry and Biology of ADP-Ribosylation-Dependent Signaling

Award Number: R35GM137901

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2020

PERIOD OF PERFORMANCE END DATE: 03/31/2031

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