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The ion channel TRPA1 is required for suppression of inflammation

Award Number: R01GM132672
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: 05/01/2019
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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The ion channel TRPA1 is required for suppression of inflammation - Project Summary/Abstract Inflammation, the essential biological response to infection and injury, is tightly controlled by the nervous system. Inflammatory cytokines and other mediators produced by immune cells during infection and injury activate sensory action potentials in the vagus nerve. The arrival of these incoming signals stimulates brain neural circuits to initiate a reflex response that return to the body and regulate cytokine production. We recently identified a critical role for the transient receptor potential ankyrin-1 (TRPA1) in mediating interleukin-1β-specific biological responses. Sensory signals transmitted via vagus TRPA1-stimulation inhibit endotoxin-induced cytokine storm and significantly reduce the lethality of bacterial sepsis. Despite the direct evidence of vagus TRPA1-mediated afferent signaling, almost nothing is known about the brain neural networks activated by vagus TRPA1 signaling and regulating inflammation. Our long-term goal is to reveal neural circuits regulating the onset and progression of inflammation. These discoveries will facilitate the design of novel therapeutic strategies targeting neural circuits for the treatment of inflammatory conditions. The objective of this grant is to provide mechanistic insight into the brain neural networks that regulate inflammatory changes. The central hypothesis is that vagus TRPA1- elicited brain neural networks play a critical role in regulating inflammation. Here, we will leverage powerful genetic, bioelectronic and chemogenetic approaches for functional mapping to define brain neural networks activated by vagus TRPA1-signaling, and how they relay outputs to the vagus nerve to impact inflammatory responses. In Specific Aim 1, we will use genetic techniques to “label” subsets of neurons selectively activated by vagus sensory signals. In Specific Aim 2, we will use viral vectors and chemogenetic tools to selectively modulate these brain networks to assess its impact on inflammation and vagus nerve signaling. Upon conclusion, the proposed studies will establish the mechanistic understanding of TRPA1-elicited brain neural networks that can be targeted by several available brain stimulating modalities using invasive and noninvasive technologies to regulate inflammation. 1


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 = $351,750 )
2025	2025	THE FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Biomedical Research and Research Training	000	5	8/27/2025	COMPETING CONTINUATION	$351,750
														Subtotal = $351,750

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	THE FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Biomedical Research and Research Training	000	4	8/26/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $335,000 )
2022	2022	FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH, THE	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Biomedical Research and Research Training	000	4	2/8/2022	NON-COMPETING CONTINUATION	$301,500
2022	2022	FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH, THE	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Biomedical Research and Research Training	001	4	6/9/2022	NON-COMPETING CONTINUATION	$33,500
														Subtotal = $335,000

Issue Date FY: 2021 ( Subtotal = $335,000 )
2021	2021	FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH, THE	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Biomedical Research and Research Training	000	3	2/19/2021	NON-COMPETING CONTINUATION	$335,000
														Subtotal = $335,000

Issue Date FY: 2020 ( Subtotal = $335,000 )
2020	2020	FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH, THE	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Biomedical Research and Research Training	000	2	2/7/2020	NON-COMPETING CONTINUATION	$335,000
														Subtotal = $335,000

Issue Date FY: 2019 ( Subtotal = $335,000 )
2019	2019	FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH, THE	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Biomedical Research and Research Training	000	1	4/19/2019	NEW	$335,000
														Subtotal = $335,000

Grand Total All Awards = $1,691,750

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The ion channel TRPA1 is required for suppression of inflammation

Award Number: R01GM132672

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: 05/01/2019

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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