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Using siglecs and their ligands to treat allergic diseases SALTAD

Award Number: U19AI136443
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: 02/06/2018
PERIOD OF PERFORMANCE END DATE: 01/31/2024

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Using siglecs and their ligands to treat allergic diseases SALTAD - OVERALL ABSTRACT Mast cells and eosinophils are essential effector cells in both acute and chronic allergic inflammatory responses. The overall goal of this Program is to exploit eosinophil and mast cell Siglecs (sialic acid binding, immunoglobulin-like lectins) to prevent or treat immediate allergic reactions and chronic allergic inflammation. The overarching hypothesis is that specific mAbs, endogenous tissue glycans, or synthetic ligand analogs, can specifically and selectively engage complementary glycan binding Siglecs (CD33, Siglec-6, and Siglec-8) on eosinophils and/or mast cells to prevent or limit IgE-dependent and IgE-independent eosinophil and mast cell- related allergic responses. This application focuses on the role of three mast cell and eosinophil Siglecs that we hypothesize provide ideal targets for dampening allergic effector cell responses in a variety of acute and chronic allergy-related disorders. Dr. Bruce Bochner will serve as the PI of Project 1 (Defining Siglec-6 and Siglec-8 function on effector cells of allergic diseases as well as Core A (Administration) and Core B (Human mast cell and tissue acquisition core). Dr. James Paulson will serve as the PI of Project 2 (Siglec-targeted nanoparticles for treating mast cell mediated allergic disease) while Dr. Ronald Schnaar will serve as the PI of Project 3 (Human siglec ligands control mast cell and eosinophil mediated inflammation). This is a Program team with a proven track record of productivity and synergy. This application includes projects that examine Siglec/eosinophil/mast cell pathways from various perspectives including pharmacology, biochemistry, cell signaling, glycobiology, and cellular and molecular biology, using in vitro experimentation and in vivo humanized models. The majority of the proposed research utilizes human material including primary human cells and biologic samples, along with animal models involving humanized mast cell mice and novel knock-in strains of mice expressing human Siglecs of interest to provide more in-depth hypothesis testing on mechanisms and outcomes that cannot yet be assessed with human research. Each Project provides numerous elements of novelty ranging from human Siglec knock-in mice to development of unique reagents for targeting specific Siglecs to discovery of endogenous human tissue ligands for specific Siglecs.


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 = -$49,069 )
2024	2022	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	5	8/20/2024	NON-COMPETING CONTINUATION	-$49,069
														Subtotal = -$49,069

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	5	1/17/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $1,505,741 )
2022	2022	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	001	5	1/19/2022	NON-COMPETING CONTINUATION	$1,505,741
2022	2021	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	4	12/27/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,505,741

Issue Date FY: 2021 ( Subtotal = $1,516,002 )
2021	2021	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	4	1/22/2021	NON-COMPETING CONTINUATION	$1,516,002
														Subtotal = $1,516,002

Issue Date FY: 2020 ( Subtotal = $1,504,730 )
2020	2020	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	3	2/4/2020	NON-COMPETING CONTINUATION	$1,504,730
														Subtotal = $1,504,730

Issue Date FY: 2019 ( Subtotal = $1,517,513 )
2019	2019	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	001	2	9/4/2019	NON-COMPETING CONTINUATION	$0
2019	2019	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	2	1/23/2019	NON-COMPETING CONTINUATION	$1,517,513
														Subtotal = $1,517,513

Issue Date FY: 2018 ( Subtotal = $1,556,002 )
2018	2018	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Allergy and Infectious Diseases Research	000	1	2/6/2018	NEW	$1,556,002
														Subtotal = $1,556,002

Grand Total All Awards = $7,550,919

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Using siglecs and their ligands to treat allergic diseases SALTAD

Award Number: U19AI136443

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: 02/06/2018

PERIOD OF PERFORMANCE END DATE: 01/31/2024

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