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Elucidating the role of DNA methyltransferases in epigenetic regulation of retinal regeneration in zebrafish

Award Number: F30EY031142
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 04/01/2020
PERIOD OF PERFORMANCE END DATE: 03/31/2025

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Elucidating the role of DNA methyltransferases in epigenetic regulation of retinal regeneration in zebrafish - Project Abstract According to the National Eye Institute, there are currently over 12 million Americans suffering from diseases affecting the retina. To present, therapeutic attempts to reduce retinal death or replace lost neurons have been met with limited success, highlighting the need for an alternative approach to this problem. The zebrafish is becoming an increasingly popular model to study mechanisms of stem-cell based tissue regeneration. In response to extensive retinal injury, zebrafish are able to completely regenerate the retina. This is accomplished through the induction of Müller glial cells which undergo an asymmetric division to generate a pool of progenitor cells that go on to regenerate all cell types of the retina with no evidence of the glial scarring observed in mammalian species. While the remarkable capacity of the zebrafish to regenerate tissues has been known for years, our understanding of the comparative biology between mammalian and teleost responses to retinal damage remains poorly understood. To present, studies of retinal regeneration in the zebrafish have largely focused on identifying signaling pathways and individual genes involved in retinal regeneration. The epigenetic orchestration of these pathways, however, remains to be investigated in the zebrafish. DNA methyltransferases (Dnmts) have been studied extensively in mammals and have been identified as critical in the homeostatic maintenance of adult stem cell processes such as hematopoietic stem cell development. The limited literature of epigenetic regulators in zebrafish reveals that teleost species appear to utilize the same mechanisms of epigenetic regulation as mammalian species, with zebrafish Dnmts baring considerable sequence homology to mammalian Dnmts. It is known that immediately following retinal injury in the zebrafish there is an initial global DNA hypomethylation and subsequent increase in DNA methylation as the pools of progenitor cells begin to differentiate, indicating the importance of the epigenetic landscape during these processes. With the experiments planned in this proposal, we aim to identify the role of Dnmts in orchestrating the process of adult retinal regeneration in the zebrafish, with the goal of elucidating pathways regulated in Müller glial derived progenitor cells at the epigenetic level. We also plan to develop a new tool that will be an important addition to the zebrafish community for investigation of the consequences of targeted epigenetic modulation of specific genes. These proposed studies will illuminate candidate genes for targeted therapeutic approaches to identify and “unlock” pathways in mammalian systems that are epigenetically silenced, opening new avenues for future studies in the field of regenerative medicine.


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: 2026 ( Subtotal = -$9,807 )
2026	2024	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Vision Research	000	5	1/29/2026	NON-COMPETING CONTINUATION	-$9,807
														Subtotal = -$9,807

Issue Date FY: 2024 ( Subtotal = $53,974 )
2024	2024	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Vision Research	001	5	6/14/2024	NON-COMPETING CONTINUATION	$1,280
2024	2024	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Vision Research	000	5	3/20/2024	NON-COMPETING CONTINUATION	$52,694
														Subtotal = $53,974

Issue Date FY: 2023 ( Subtotal = $52,694 )
2023	2023	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Vision Research	000	4	3/31/2023	NON-COMPETING CONTINUATION	$52,694
														Subtotal = $52,694

Issue Date FY: 2022 ( Subtotal = $44,746 )
2022	2022	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Vision Research	001	3	5/9/2022	NON-COMPETING CONTINUATION	$717
2022	2022	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Vision Research	000	3	4/5/2022	NON-COMPETING CONTINUATION	$44,030
2022	2022	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Vision Research	002	3	7/1/2022	NON-COMPETING CONTINUATION	-$1
														Subtotal = $44,746

Issue Date FY: 2021 ( Subtotal = $44,030 )
2021	2021	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Vision Research	000	2	4/1/2021	NON-COMPETING CONTINUATION	$44,030
														Subtotal = $44,030

Issue Date FY: 2020 ( Subtotal = $43,514 )
2020	2020	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Vision Research	001	1	1/23/2020	NEW	$0
2020	2020	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Vision Research	000	1	1/23/2020	NEW	$43,010
2020	2020	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Vision Research	002	1	6/26/2020	NEW	$504
														Subtotal = $43,514

Grand Total All Awards = $229,151

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Elucidating the role of DNA methyltransferases in epigenetic regulation of retinal regeneration in zebrafish

Award Number: F30EY031142

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 04/01/2020

PERIOD OF PERFORMANCE END DATE: 03/31/2025

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