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Unraveling the role of HLA-B51/ERAP1 in Behcet's eye disease

Award Number: R01EY031383
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2021
PERIOD OF PERFORMANCE END DATE: 11/30/2025

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Unraveling the role of HLA-B51/ERAP1 in Behcet's eye disease - ABSTRACT / PROJECT SUMMARY HLA-B*51 in epistasis with the ERAP1 haplotype Hap10 confers the strongest currently known risk for Behcet’s Disease (BD) and Behcet’s Eye Disease (BED), but the consequences of this relationship for immune-phenotype, clonality, and function, are entirely unknown. The main objective of this application is to identify these consequences. This is in line with our long-term goal to find, comprehend, and correct aberrancies in immune pathways that drive Behcet’s Eye Disease (BED). Based on our preliminary studies we propose as our central hypothesis that ERAP1 Hap10 shapes immune responses in HLA-B*51+ BED through the activation of clonal CD8 T and NKT effector cell populations that drive the disease. We follow the rationale that elucidation of the biological consequences of HLA-B51/ERAP1 Hap10 will promote a mechanistic understanding of BED in affected carriers, and therefore enable targeted therapy design. We will test our central hypothesis in two specific aims: 1) Through the determination of immune phenotypes linked to HLA-B*51+/ERAP1 Hap10 BED, combining access to unique patient cohorts of our own and those of our international collaborators with large-scale flow cytometric analyses using computational tools we have developed. 2) Through the identification of clonal effector responses and function in BED patients using single cell-transcriptomics and methods of T cell cloning we have established. Meeting the objective of this proposal will generate knowledge providing scientific rationale for the design of targeted therapies for BED, which is one of the most devastating forms of non-infectious uveitis with significant prevalence in large parts of the world. We expect additional positive impact by cross-fertilizing research of other HLA-I/ERAP-related diseases including HLA-B27-associated uveitis and spondylitis, Birdshot’s choroidopathy, psoriasis-associated conditions, and inflammatory bowel disease (IBD).


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 = $423,750 )
2025	2025	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	000	5	12/4/2024	NON-COMPETING CONTINUATION	$423,750
														Subtotal = $423,750

Issue Date FY: 2024 ( Subtotal = $423,750 )
2024	2024	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	000	4	12/8/2023	NON-COMPETING CONTINUATION	$423,750
2024	2024	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	001	4	5/22/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $423,750

Issue Date FY: 2023 ( Subtotal = $423,751 )
2023	2023	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	001	3	3/6/2023	NON-COMPETING CONTINUATION	$42,374
2023	2023	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	000	3	12/8/2022	NON-COMPETING CONTINUATION	$381,377
														Subtotal = $423,751

Issue Date FY: 2022 ( Subtotal = $411,038 )
2022	2022	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	000	2	12/3/2021	NON-COMPETING CONTINUATION	$381,375
2022	2022	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	001	2	5/4/2022	NON-COMPETING CONTINUATION	$29,663
														Subtotal = $411,038

Issue Date FY: 2021 ( Subtotal = $423,750 )
2021	2021	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	000	1	1/14/2021	NEW	$423,750
														Subtotal = $423,750

Grand Total All Awards = $2,106,039

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Unraveling the role of HLA-B51/ERAP1 in Behcet's eye disease

Award Number: R01EY031383

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2021

PERIOD OF PERFORMANCE END DATE: 11/30/2025

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