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Integrated genetic, omic, and immunologic studies to identify endotypes and novel drug targets for asthma and allergic diseases

Award Number: U19AI162310
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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ABSTRACT Asthma and allergic diseases are among the most common chronic diseases in children and adults, costing our health care system over $80 billion per year. Rates have been increasing over the past 40 years and therapeutic advances have been incremental. Over 150 loci have been reported in large genome-wide association studies (GWAS) of asthma and allergic diseases, but their individual effects are small and these variants account a small fraction of the overall genetic risk. Moreover, remarkably few of the GWAS findings for asthma and allergic diseases have led to discoveries of causal variants or causal genes that contribute to asthma and allergic disease pathogenesis. The latter has been particularly challenging due in part to the significant clinical heterogeneity of these diseases, and in part to the lag in the development of powerful statistical, molecular, and immunologic tools for bridging the trajectory from GWAS to gene discovery to biology to translation. In this application, we propose a robust and comprehensive strategy for identifying candidate causal variants and their target genes at asthma and allergic disease-associated loci, and for characterizing (i) their functional effects in asthma and allergic disease-relevant cells types, including bronchial epithelial cells, airway smooth muscle and lung immune cells, as well as peripheral immune cells, all in resting and activated states; (ii) their downstream phenotypic effects on both broad categories of disease groups and traits in the UK Biobank resource and on specific asthma and allergic disease endotypes in deeply phenotyped ethnically-diverse subjects participating in asthma birth cohorts; and (iii) their immunologic effects in resting and activated lung lymphocytes and myeloid cells and in “humanized locus” BAC-engineered mouse models. These goals will be accomplished through a highly collaborative and synergistic program that includes two projects, a service core, and an administrative core that together will that bridge the trajectory from GWAS to translation through highly integrated studies by an exceptional team of investigators with expertise in genetics, (epi)genomics, statistical genetics, and immunology. Achieving these goals will ultimately identify novel drug targets and the individuals most likely to respond, providing a framework for precision medicine and personalized treatment of asthma and allergic diseases.


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 = $1,441,202 )
2024	2024	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	000	4	4/22/2024	NON-COMPETING CONTINUATION	$1,441,202
														Subtotal = $1,441,202

Issue Date FY: 2023 ( Subtotal = $1,797,510 )
2023	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	003	3	8/1/2023	NON-COMPETING CONTINUATION	$346,475
2023	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	002	3	4/12/2023	NON-COMPETING CONTINUATION	$1,451,035
2023	2022	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	000	2	2/22/2023	NON-COMPETING CONTINUATION	$0
2023	2022	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	001	2	2/27/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,797,510

Issue Date FY: 2022 ( Subtotal = $1,460,586 )
2022	2022	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	000	2	4/29/2022	NON-COMPETING CONTINUATION	$1,460,586
2022	2022	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	001	2	8/10/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,460,586

Issue Date FY: 2021 ( Subtotal = $1,391,652 )
2021	2021	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	000	1	7/19/2021	NEW	$1,391,652
														Subtotal = $1,391,652

Grand Total All Awards = $6,090,950

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Integrated genetic, omic, and immunologic studies to identify endotypes and novel drug targets for asthma and allergic diseases

Award Number: U19AI162310

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

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