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Genetic and microbial modifiers of Atopic Dermatitis (AD): Mechanisms of increased AD severity in patients with the R576 polymorphism in IL-4Ra and impact of S aureus skin decolonization on AD

Award Number: U01AI152033
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2020
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Genetic and microbial modifiers of Atopic Dermatitis (AD): Mechanisms of increased AD severity in patients with the R576 polymorphism in IL-4Ra and impact of S aureus skin decolonization on AD - This ADRN-CRC application brings together seasoned clinical and laboratory investigators in atopic dermatitis (AD), with expertise in clinical research, immunology, S aureus biology, dermatology, and statistics. The investigators have long track records in implementing multi-center and single-center clinical trials and observational studies in allergic diseases, including AD, to the standards of NIH funded clinical research networks, in conducting NIH fundamental research on disease mechanisms in AD and in training generations of investigators in AD research In part A we demonstrate that we have the personnel and facilities to conduct ADRN network-wide and CRC center-specific research on pediatric and adult AD patient populations recruited from the allergy and dermatology clinics at Boston Children's Hospital and collaborating adult centers at the Brigham and Women's Hospital Mas General Hospital and Boston University Medical Center and Hospital, and from our just completed, as well as ongoing, NIH-funded studies of schoolchildren with allergic diseases. We have a highly experienced team, IRB-approved protocols for recruitment and clinical characterization of AD patients, an infrastructure which includes clinical research facilities, investigational pharmacy services, a laboratory facility capable of processing, storing and shipping human samples, a state-of-the-art immunology research laboratory with a 25 year focus on AD, and a data management facility with quality control plans, and capability to upload data into the NIAID designated repositories and biostatistical support. Project I in part B will draw on an already genotyped local population of AD patients to test the hypothesis that the IL-4Rα R576 polymorphism is associated with increased AD severity and alterations in the function and gene expression of epidermal and immune cells. We will also use a mouse model of AD to test the hypothesis that both epidermal and immune cells contribute to the increased antigen allergic skin inflammation observed in mice with the IL-4Rα R576R polymorphism. Project II in part B will test the hypothesis that S. aureus skin decolonization in AD will reduce disease severity and favorably alter the function and gene expression of epidermal and immune cells that contribute to disease severity. We will also test the hypothesis that S. aureus skin colonization promotes the development of antigen-driven allergic skin inflammation, and its reactivation, using a mouse model of AD. Our proposal will contribute extensively to the ADRN as a Clinical Research Unit and, as an ADRN-CRC will help elucidate the role of genetic and microbial modifiers in AD. !


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 = $510,170 )
2025	2025	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	6	3/11/2025	NON-COMPETING CONTINUATION	$510,170
														Subtotal = $510,170

Issue Date FY: 2024 ( Subtotal = $526,128 )
2024	2024	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	002	5	4/4/2024	NON-COMPETING CONTINUATION	$526,128
2024	2023	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	003	4	7/25/2024	NON-COMPETING CONTINUATION	$0
2024	2023	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	4	4/3/2024	NON-COMPETING CONTINUATION	$0
2024	2022	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	3	4/2/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $526,128

Issue Date FY: 2023 ( Subtotal = $526,458 )
2023	2023	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	4	3/13/2023	NON-COMPETING CONTINUATION	$526,458
2023	2022	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	3	3/17/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $526,458

Issue Date FY: 2022 ( Subtotal = $526,470 )
2022	2022	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	3	3/10/2022	NON-COMPETING CONTINUATION	$526,470
2022	2022	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	002	3	7/1/2022	NON-COMPETING CONTINUATION	$0
2022	2021	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	2	11/23/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $526,470

Issue Date FY: 2021 ( Subtotal = $527,288 )
2021	2021	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	2	4/1/2021	NON-COMPETING CONTINUATION	$527,288
														Subtotal = $527,288

Issue Date FY: 2020 ( Subtotal = $530,679 )
2020	2020	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	1	4/1/2020	NEW	$530,679
														Subtotal = $530,679

Grand Total All Awards = $3,147,193

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Genetic and microbial modifiers of Atopic Dermatitis (AD): Mechanisms of increased AD severity in patients with the R576 polymorphism in IL-4Ra and impact of S aureus skin decolonization on AD

Award Number: U01AI152033

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 04/01/2020

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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