Thursday, February 19, 2026 2/19/2026

STRUCTURE AND FUNCTION OF MRG-FAMILY RECEPTORS

Award Number: R01DA055656
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2022
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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STRUCTURE AND FUNCTION OF MRG-FAMILY RECEPTORS - ABSTRACT Chronic pain impacts a large proportion of the US population with estimates ranging from 10-40% of adults. Opioids and related medications are among the most frequently prescribed medications for treating chronic pain, albeit with considerable risks due to overdose, constipation, addiction and other serious side-effects. Over the past decades our understanding of the neural circuitry responsible for nociception and anti-nociceptive therapies has revealed several molecular targets that are potential therapeutic targets for non-opioid pain relieving medication. Among these are the Mas-related G protein coupled receptors (MRGPRs). The first MRGPR was discovered in 1986 and since then they have been found to encompass an ~40-member family of GPCRs that are highly localized to primary sensory ganglia. MRGPRs are divided into 9 major families (viz. MRGPRA through MRGPRH and MRGPRX) and, of these, the MRGPRX-family of receptors has been highlighted as a ‘primate-exclusive’ group enriched in human sensory neurons. We have recently shown that MRGPRX2 likely mediates the mast-cell dependent hypersensitivity responses caused by prescription opioids and related medications. We have also with collaborators reported that a polymorphism in MRGPRX4 mediates the preference for mentholated cigarettes among individuals with African ancestry. The mechanism(s) by which opioids and other drugs interact with MRGPR-receptors is unknown and here we will elucidate their mechanism(s) by structural biological investigation of these enigmatic receptors. Using these structures we will discover and optimize chemical tools with which to modulate their function. These studies will lead to an enhanced understanding of MRGPR-receptor structure and function. The findings may accelerate the search for medications devoid of MRGPR-mediated side effects and which may function as therapies for diseases linked to MRGPR-receptor dysfunction.


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 = $559,248 )
2026	2026	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Drug Use and Addiction Research Programs	001	5	2/6/2026	NON-COMPETING CONTINUATION	$55,924
2026	2026	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Drug Use and Addiction Research Programs	000	5	1/30/2026	NON-COMPETING CONTINUATION	$503,324
														Subtotal = $559,248

Issue Date FY: 2025 ( Subtotal = $563,447 )
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Drug Use and Addiction Research Programs	000	4	1/27/2025	NON-COMPETING CONTINUATION	$507,103
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Drug Use and Addiction Research Programs	001	4	4/9/2025	NON-COMPETING CONTINUATION	$56,344
														Subtotal = $563,447

Issue Date FY: 2024 ( Subtotal = $563,447 )
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Drug Use and Addiction Research Programs	000	3	1/11/2024	NON-COMPETING CONTINUATION	$507,103
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Drug Use and Addiction Research Programs	001	3	4/25/2024	NON-COMPETING CONTINUATION	$56,344
														Subtotal = $563,447

Issue Date FY: 2023 ( Subtotal = $566,946 )
2023	2023	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Drug Use and Addiction Research Programs	000	2	1/11/2023	NON-COMPETING CONTINUATION	$566,946
														Subtotal = $566,946

Issue Date FY: 2022 ( Subtotal = $582,640 )
2022	2022	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Drug Use and Addiction Research Programs	000	1	3/16/2022	NEW	$582,640
														Subtotal = $582,640

Grand Total All Awards = $2,835,728

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STRUCTURE AND FUNCTION OF MRG-FAMILY RECEPTORS

Award Number: R01DA055656

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2022

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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