Wednesday, February 5, 2025 2/5/2025

Investigating astrocytic RIPK3 as a driver of protective neuroinflammation during viral encephalitis

Award Number: R01NS120895
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Abstract Astrocytes are versatile glial cells that regulate diverse processes in the central nervous system (CNS). Roles for astrocytes during disease are complex and include both protective and pathologic functions. Recently, distinct astrocyte activation states have been described, though the molecular mechanisms that govern astrocyte polarization during neurotropic viral infection are not well understood. Here, we propose that receptor-interacting protein kinase-3 (RIPK3) is a previously unappreciated driver of inflammatory astrocyte activation during viral infection of the CNS. While roles for RIPK3 in programmed cell death have been extensively characterized, our published work has described pleiotropic, cell death-independent functions for this pathway in the coordination of protective neuroinflammation during viral encephalitis. In preliminary studies, we now show that RIPK3 signaling in astrocytes is required for survival and virologic control following challenge with Zika virus, an emerging neurotropic pathogen of global concern. Using a combination of novel mouse genetic tools, we will elucidate roles for RIPK3 signaling in astrocytes by 1) Defining profiles of expression, activation, and antiviral function for astrocytic RIPK3; 2) Determining roles for astrocytic RIPK3 signaling in coordinating neuroinflammation; and 3) Defining key substrates and transcriptional outputs of RIPK3 signaling in astrocytes. Together, our studies promise to identify new molecular mechanisms governing protective neuroimmune function during viral encephalitis.


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 = $344,427 )
2025	2025	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	1/23/2025	NON-COMPETING CONTINUATION	$344,427
2025	2024	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	12/17/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $344,427

Issue Date FY: 2024 ( Subtotal = $304,686 )
2024	2024	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	4	4/24/2024	NON-COMPETING CONTINUATION	$17,966
2024	2024	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	1/17/2024	NON-COMPETING CONTINUATION	$353,250
2024	2024	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	4	2/9/2024	SUPPLEMENT FOR EXPANSION	-$83,816
2024	2024	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	1/23/2024	SUPPLEMENT FOR EXPANSION	$83,816
2024	2023	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	2/9/2024	SUPPLEMENT FOR EXPANSION	-$66,530
														Subtotal = $304,686

Issue Date FY: 2023 ( Subtotal = $503,644 )
2023	2023	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	6/9/2023	NON-COMPETING CONTINUATION	$382,697
2023	2023	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	3	8/23/2023	SUPPLEMENT FOR EXPANSION	$83,816
2023	2023	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	8/3/2023	SUPPLEMENT FOR EXPANSION	$37,131
2023	2023	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	8/22/2023	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $503,644

Issue Date FY: 2022 ( Subtotal = $555,632 )
2022	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	1/12/2022	NON-COMPETING CONTINUATION	$344,427
2022	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	2	3/28/2022	NON-COMPETING CONTINUATION	$38,270
2022	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	2	1/20/2022	SUPPLEMENT FOR EXPANSION	$83,626
2022	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	005	2	7/14/2022	SUPPLEMENT FOR EXPANSION	$51,988
2022	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	2	1/31/2022	SUPPLEMENT FOR EXPANSION	$190
2022	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	1/19/2022	SUPPLEMENT FOR EXPANSION	$37,131
														Subtotal = $555,632

Issue Date FY: 2021 ( Subtotal = $433,710 )
2021	2021	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	7/14/2021	SUPPLEMENT FOR EXPANSION	$51,983
2021	2021	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	2/3/2021	NEW	$381,727
														Subtotal = $433,710

Grand Total All Awards = $2,142,099

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Investigating astrocytic RIPK3 as a driver of protective neuroinflammation during viral encephalitis

Award Number: R01NS120895

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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