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Activation of Wnt signaling using PF-04802367 in human limbal epithelial stem cell self-renewal (Chloe Moore)

Award Number: R01EY021797
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2012
PERIOD OF PERFORMANCE END DATE: 01/31/2025

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Activation of Wnt signaling using PF-04802367 in human limbal epithelial stem cell self-renewal (Chloe Moore) - PROJECT SUMMARY Limbal epithelial stem/progenitor cells (LSCs) in the human corneal epithelium are the front line of defense to maintain transparency of the cornea. Loss or dysfunction of the LSCs leads to limbal stem cell deficiency (LSCD), which causes pain, inflammation, and loss of corneal transparency in patients. Cultivated LSCs from a patient’s healthy LSCs can be transplanted into the diseased cornea to replenish the LSCs, but maintaining sufficient LSCs and preventing LSC differentiation in culture to allow for a successful transplant remain a major challenge in the field. A canonical Wnt mimic small molecule and the expression of the Wnt co-receptor and putative LSC marker Fzd7 have separately been shown to improve the cultivation of LSCs while preventing differentiation. The goal of this proposal is to investigate a new small molecule PF- 04802367 which activates the β-catenin pathway by inhibiting GSK-3β to activate canonical Wnt signaling. The kinetics of Wnt activation will be investigated using a TopFlash assay first. The function and population of cultivated LSCs following PF-04802367 treatment will be evaluated as described using biomarkers in the parent grant. The proposed project will inform further development of Wnt mimic small molecule PF-04802367 to maximize the population of undifferentiated LSCs in culture. The knowledge gained from the proposed project will allow continued improvement of patient-specific LSCD treatment.


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 = -$4,383 )
2025	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Vision Research	000	10	6/10/2025	NON-COMPETING CONTINUATION	-$3,978
2025	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Vision Research	001	10	6/10/2025	SUPPLEMENT FOR EXPANSION	-$405
														Subtotal = -$4,383

Issue Date FY: 2023 ( Subtotal = $429,660 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Vision Research	000	10	2/10/2023	NON-COMPETING CONTINUATION	$390,000
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Vision Research	002	10	6/20/2023	SUPPLEMENT FOR EXPANSION	$19,830
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Vision Research	001	10	6/16/2023	SUPPLEMENT FOR EXPANSION	$19,830
														Subtotal = $429,660

Issue Date FY: 2022 ( Subtotal = $413,382 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Vision Research	003	9	7/1/2022	SUPPLEMENT FOR EXPANSION	$17,541
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Vision Research	002	9	6/29/2022	SUPPLEMENT FOR EXPANSION	$0
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Vision Research	000	9	5/23/2022	NON-COMPETING CONTINUATION	$378,300
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Vision Research	001	9	6/16/2022	SUPPLEMENT FOR EXPANSION	$17,541
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Vision Research	004	9	7/7/2022	SUPPLEMENT FOR EXPANSION	$0
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Vision Research	005	9	7/7/2022	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $413,382

Issue Date FY: 2021 ( Subtotal = $378,300 )
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Vision Research	000	8	4/15/2021	NON-COMPETING CONTINUATION	$378,300
														Subtotal = $378,300

Issue Date FY: 2020 ( Subtotal = $390,000 )
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Vision Research	001	7	2/11/2020	NON-COMPETING CONTINUATION	$390,000
2020	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Vision Research	000	6	2/11/2020	COMPETING CONTINUATION	$0
														Subtotal = $390,000

Issue Date FY: 2019 ( Subtotal = $390,000 )
2019	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Vision Research	000	6	1/24/2019	COMPETING CONTINUATION	$390,000
2019	2016	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Vision Research	001	5	2/6/2019	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $390,000

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2016	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Vision Research	001	5	1/29/2017	EXTENSION WITH OR WITHOUT FUNDS	$10,537
2017	2015	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Vision Research	000	4	1/29/2017	NON-COMPETING CONTINUATION	-$10,537
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $385,000 )
2016	2016	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Vision Research	000	5	9/8/2016	EXTENSION WITH OR WITHOUT FUNDS	$385,000
														Subtotal = $385,000

Issue Date FY: 2015 ( Subtotal = $377,300 )
2015	2015	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Vision Research	000	4	8/17/2015	NON-COMPETING CONTINUATION	$377,300
														Subtotal = $377,300

Issue Date FY: 2014 ( Subtotal = $377,300 )
2014	2014	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Vision Research	000	3	7/21/2014	NON-COMPETING CONTINUATION	$377,300
														Subtotal = $377,300

Issue Date FY: 2013 ( Subtotal = $365,750 )
2013	2013	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Vision Research	000	2	7/30/2013	NON-COMPETING CONTINUATION	$365,750
														Subtotal = $365,750

Issue Date FY: 2012 ( Subtotal = $385,000 )
2012	2012	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Vision Research	000	1	8/14/2012	NEW	$385,000
														Subtotal = $385,000

Grand Total All Awards = $3,887,309

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Activation of Wnt signaling using PF-04802367 in human limbal epithelial stem cell self-renewal (Chloe Moore)

Award Number: R01EY021797

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2012

PERIOD OF PERFORMANCE END DATE: 01/31/2025

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