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Understanding the role of S. aureus agr virulence in atopic dermatitis

Award Number: K01AR078931
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 06/01/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Understanding the role of S. aureus agr virulence in atopic dermatitis - Project Summary Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects 15-30% of children and approximately 5% of adults in industrialized countries. However, effective treatments to prevent and treat this skin disease are lacking due in part to an incomplete understanding of the disease. The human pathogen Staphylococcus aureus has been linked to AD pathogenesis because more than 90% of AD patients are colonized in the lesional skin with the pathogen. Although S. aureus can produce multiple virulence factors, the mechanism by which S. aureus virulence contributes to AD remains unknown. Using a recently developed mouse model of epicutaneous S. aureus infection that resembles that observed in AD flares, we found that activation of the S. aureus accessory gene regulatory (Agr) quorum-sensing system induces the release of keratinocyte alarmins to trigger skin inflammation. We hypothesize that S. aureus Agr virulence factors play a critical role in skin inflammation associated with AD. We propose three Aims to test our hypotheses: 1) Use a novel AD mouse model to study the role of S. aureus in skin inflammation; 2) Determine the mechanism of S. aureus colonization in the skin and upregulation of Agr expression in lesional skin using the AD-like mouse model; 3) Examine the expression of S. aureus Agr virulence genes in lesional and non-lesional skin of AD patients and the function of AD- associated S. aureus in skin inflammation. These studies will provide critical insight into AD pathogenesis that will help the development of new approaches to treat AD. The candidate is a basic immunologist and Research Investigator at the University of Michigan. Under the guidance of his mentors and advisory team, he will acquire new knowledge and research expertise to test the hypothesis that both S. aureus Agr virulence and skin factors are important for triggering skin inflammation in AD using a newly developed AD model. The research proposed in his K01 application is a new scientific challenge in his career that offers the opportunities to integrate clinical and translational experience with his comprehensive training in basic science. Dr. Matsumoto's career development goals will be supported through close mentorship from an interdisciplinary team, advanced didactic coursework, attendance at professional meetings and workshops, participation in regular seminars, guidance in manuscript preparation and grant proposal development. This training and research activities will provide him with the necessary skills and experience needed to become a successful independent translational investigator.


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 = $90,834 )
2025	2025	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	5/6/2025	NON-COMPETING CONTINUATION	$90,834
														Subtotal = $90,834

Issue Date FY: 2024 ( Subtotal = $90,834 )
2024	2024	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Arthritis, Musculoskeletal and Skin Diseases Research	005	4	8/5/2024	NON-COMPETING CONTINUATION	$90,834
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Arthritis, Musculoskeletal and Skin Diseases Research	004	4	7/30/2024	NON-COMPETING CONTINUATION	-$90,834
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	4	7/17/2024	NON-COMPETING CONTINUATION	$90,834
2024	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	2	7/1/2024	NON-COMPETING CONTINUATION	$0
2024	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	5/16/2024	NON-COMPETING CONTINUATION	-$70,857
2024	2023	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	3	5/16/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$70,857
														Subtotal = $90,834

Issue Date FY: 2023 ( Subtotal = $90,834 )
2023	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	6/8/2023	NON-COMPETING CONTINUATION	$90,834
														Subtotal = $90,834

Issue Date FY: 2022 ( Subtotal = $90,834 )
2022	2022	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	5/31/2022	NEW	$90,834
														Subtotal = $90,834

Grand Total All Awards = $363,336

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Understanding the role of S. aureus agr virulence in atopic dermatitis

Award Number: K01AR078931

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 06/01/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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