Monday, June 30, 2025 6/30/2025

THE UBIQUITIN PATHWAY IN CORNEAL SCARRING

Award Number: R01EY024942
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2015
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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THE UBIQUITIN PATHWAY IN CORNEAL SCARRING - Project Summary: The ubiquitin pathway in corneal scarring Scarring in the cornea resulting from injury, trauma, or infection can lead to debilitating opacities and permanent vision loss. Acute scarring, similar to chronic fibrosis, is characterized by immune cell infiltration and the persistence of cells termed myofibroblasts. We have found that the deubiquitinase (DUB) USP10 is a key regulator of scarring pathways in the cornea. Knockdown of USP10 in vivo leads to a significant reduction in the development of myofibroblasts, cell apoptosis, the presence of CD45+ immune cells, and fibrotic extracellular matrix in a healing wound. We are proposing to test the central hypothesis that USP10 is a key regulator of myofibroblast persistence in a corneal scar via its multi- factorial role in wound healing. Specifically, since USP10 is a DUB for αv-integrins and p53, in Specific Aim 1 we will unravel the complex role of USP10 in integrin recycling and p53 dynamics in primary human corneal fibroblasts and in mice in vivo. The communication between fibroblasts and macrophages plays a critical role in scarring outcomes. In Specific Aim 2 we will develop novel 3D and 2.5D hydrogel systems with “tunable stiffness” that mimic a 3D environment close to the stiffness of the healing cornea. Using these hydrogels, mouse corneal fibroblasts will be cocultured with mouse bone marrow derived macrophages (M0/M1/M2) to elucidate the role of USP10 in macrophage-mediated myofibroblast development and contraction. In Specific Aim 3 using three separate mouse models we will assess the role of USP10 in immune cell infiltration into a corneal wound.


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 = $366,750 )
2025	2025	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Vision Research	000	7	2/14/2025	NON-COMPETING CONTINUATION	$366,750
														Subtotal = $366,750

Issue Date FY: 2024 ( Subtotal = $366,750 )
2024	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Vision Research	000	6	5/16/2024	NON-COMPETING CONTINUATION	$366,750
														Subtotal = $366,750

Issue Date FY: 2023 ( Subtotal = $366,750 )
2023	2023	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Vision Research	000	5	2/3/2023	COMPETING CONTINUATION	$366,750
														Subtotal = $366,750

Issue Date FY: 2021 ( Subtotal = -$2,674 )
2021	2018	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Vision Research	000	4	1/30/2021	NON-COMPETING CONTINUATION	-$2,674
														Subtotal = -$2,674

Issue Date FY: 2018 ( Subtotal = $402,981 )
2018	2018	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Vision Research	002	4	6/28/2018	NON-COMPETING CONTINUATION	$402,981
2018	2017	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Vision Research	001	3	2/8/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$105,485
2018	2016	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Vision Research	000	2	2/8/2018	NON-COMPETING CONTINUATION	-$105,485
														Subtotal = $402,981

Issue Date FY: 2017 ( Subtotal = $403,057 )
2017	2017	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Vision Research	000	3	8/25/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$403,057
														Subtotal = $403,057

Issue Date FY: 2016 ( Subtotal = $423,750 )
2016	2016	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL, BOX 3500	NEW YORK-NEW YORK	NY	10029		USA	Vision Research	000	2	6/8/2016	NON-COMPETING CONTINUATION	$423,750
														Subtotal = $423,750

Issue Date FY: 2015 ( Subtotal = $423,750 )
2015	2015	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL, BOX 3500	NEW YORK-NEW YORK	NY	10029		USA	Vision Research	000	1	7/23/2015	NEW	$423,750
														Subtotal = $423,750

Grand Total All Awards = $2,751,114

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THE UBIQUITIN PATHWAY IN CORNEAL SCARRING

Award Number: R01EY024942

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2015

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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