Tuesday, July 1, 2025 7/1/2025

Racial Differences in Biomarkers and Therapeutic Targets for Chronic Itch

Award Number: K23AR077073
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 05/01/2024
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Racial Differences in Biomarkers and Therapeutic Targets for Chronic Itch - Itch, or pruritus, is a commonly reported symptom with over 7 million clinician visits annually in the United States. Indeed, the Global Burden of Disease Study by the World Health Organization categorized itch in the top 50 most prevalent diseases worldwide. Itch is difficult to manage, as there are limited therapeutics. There are also racial differences in itch in skin diseases such as atopic dermatitis (AD) and prurigo nodularis (PN), which disproportionately affect African Americans (AA). AD is more likely to be papular, affect extensor areas, and less likely to be associated with filaggrin loss-of-function mutations in blacks as compared to Caucasians. This study will investigate novel itch receptors and cytokine profiles in human AD and PN patients with respect to race to provide biomarkers and potential targets for future therapeutics. Our first aim focuses on a recently discovered group of itch receptors, known as Mas-related G protein- coupled receptors (Mrgprs). In humans, there are 4 Mrgpr genes (MrgprX1-4). A role for three of the MrgprX genes in humans has been elucidated: MrgprX1 mediates chloroquine-induced itch, which disproportionally affects AA, MrgprX2 is a regulator of pseudoallergic reactions, and our recent study demonstrated a role for MrgprX4 as a bilirubin receptor mediating cholestatic pruritus, but the function of MrgprX3 is unknown. Based on preliminary data showing dramatic upregulation of MrgprX3 in lesional, pruritic, PN skin and because MrgprX3 is the most highly expressed Mrgpr in keratinocytes, this aim will determine the cellular localization, polymorphisms, and phenotypic differences in the expression of MrgprX3 in PN and AD patients with respect to itch intensity and race. Our second aim will characterize upregulation of the IL-22 cytokine pathway in PN and AD patients according to race and itch intensity. Our preliminary data reveals significant upregulation of Th22-associated genes in lesional PN and AD skin as compared to healthy skin. Further, we found robust IL-22 expression from human blood peripheral blood mononuclear cells in PN patients as compared to healthy controls. Thus, in this aim we will determine circulating levels of IL-22 from plasma and peripheral blood mononuclear cells in a larger sample of PN and AD patients with respect to race and varying itch intensity. We will also determine the expression and cellular localization of IL-22 and Th22-associated related genes in PN and AD lesional skin. Finally, we will test the hypothesis that MrgprX3 expression is regulated by IL-22 and Th22 associated genes. This project will provide important insights into the role of MrpgrX3, IL-22, and the interplay between these mediators into the pathogenesis of itch in AD and PN in African American and Caucasian patients. Importantly, the results will be correlated with race to determine the pathogenesis and novel therapeutic targets in specific patient populations. The knowledge gained from these studies will identify patients likely to benefit from future treatments aimed at targeting itch in AD and PN.


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 = $171,072 )
2024	2024	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	4	8/16/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$171,072
2024	2023	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	8/15/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $171,072

Issue Date FY: 2023 ( Subtotal = $177,120 )
2023	2023	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	6/30/2023	NON-COMPETING CONTINUATION	$177,120
														Subtotal = $177,120

Issue Date FY: 2022 ( Subtotal = $177,120 )
2022	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	6/30/2022	NON-COMPETING CONTINUATION	$177,120
														Subtotal = $177,120

Issue Date FY: 2021 ( Subtotal = $177,000 )
2021	2021	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	1	8/18/2021	NEW	$1,500
2021	2021	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	7/15/2021	NEW	$175,500
														Subtotal = $177,000

Grand Total All Awards = $702,312

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Racial Differences in Biomarkers and Therapeutic Targets for Chronic Itch

Award Number: K23AR077073

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 05/01/2024

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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