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Interrogating unique DC adaptations to tissue to promote barrier immunity and tolerance

Award Number: R01AR080436
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Interrogating unique DC adaptations to tissue to promote barrier immunity and tolerance - Project summary: The immune system faces the external world and encounters pathogens, including viruses in barrier tissues (e.g. skin, lung, and gut). There the immune system must detect and respond to pathogens, while simultaneously preventing autoimmunity and promoting tissue repair. Dendritic cells (DC) in tissue are the key cells which balance self-tolerance (preventing destruction of our bodies tissues) with pathogen surveillance. The goal of this application is to understand how DCs develop uniquely and are adapted in the tissue to perform and balance these functions. We have recently identified an important new mechanism, and a new molecular target that dictates how DC in tissues differentiate in ways that impact their function. The goal of this proposal is to gain a deeper understanding of DC biology along this regulatory axis, as a critical first step to intervene upon tissue DC to restore health, when dysregulated. This would advance better immunization strategies as tissue DCs are necessary for vaccine, viral, and cancer immunity. This application enables us to now test, for the first time, how our myeloid compartment is architected to balance immune tolerance and pathogen surveillance in barrier tissue sites. Upon completion of this project we will understand how DCs in tissue are locally conditioned to behave in a site- specific manner. We will gain an appreciation of how shared environmental sensing patterns are balanced against individual cell identities, and tailored to specific pathogenic contexts. We will understand how local cues modify the behavior of DCs, positioning us to test this in disease states. We will also identify DC behaviors that are modifiable by local cues, enabling improved intervention on DC during disease pathogenesis and a better model for successful DC development to improve adoptive cell therapy. The insights here are foundational, fill a critical knowledge gap, and represent basic science advances needed to advance human health.


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 = $655,149 )
2025	2025	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	2/19/2025	NON-COMPETING CONTINUATION	$655,149
														Subtotal = $655,149

Issue Date FY: 2024 ( Subtotal = $706,103 )
2024	2024	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	3	5/29/2024	NON-COMPETING CONTINUATION	$50,954
2024	2024	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	1/18/2024	NON-COMPETING CONTINUATION	$655,149
														Subtotal = $706,103

Issue Date FY: 2023 ( Subtotal = $732,031 )
2023	2023	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	3/28/2023	NON-COMPETING CONTINUATION	$73,202
2023	2023	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	1/26/2023	NON-COMPETING CONTINUATION	$658,829
														Subtotal = $732,031

Issue Date FY: 2022 ( Subtotal = $741,228 )
2022	2022	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	2/25/2022	NEW	$741,228
														Subtotal = $741,228

Grand Total All Awards = $2,834,511

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Interrogating unique DC adaptations to tissue to promote barrier immunity and tolerance

Award Number: R01AR080436

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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