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Study epigenetic inheritance during development, homeostasis and regeneration

Award Number: R35GM127075
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2018
PERIOD OF PERFORMANCE END DATE: 04/30/2029

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Study epigenetic inheritance during development, homeostasis and regeneration - Project Summary/Abstract: Epigenetics refers to effects on gene expression or function that are inheritable through mitosis or meiosis without altering the primary DNA sequences. Epigenetic mechanisms play important roles in regulating cell identity and activity. Failure in appropriate epigenetic regulation leads to abnormal behaviors of cells, which underlies many diseases such as diabetes, muscular dystrophy, neurodegenerative disease, infertility, and many forms of cancer. Many types of stem cells undergo asymmetric cell divisions to give rise to two daughter cells with distinct cell fates: a self-renewed stem cell and to another daughter cell that differentiates. We found that during the asymmetric division of Drosophila male germline stem cell (GSC), the preexisting histones are selectively segregated to the GSC whereas newly synthesized histones are enriched in the differentiating daughter cell. Our studies provide the first direct evidence that stem cells retain preexisting histones during asymmetric cell divisions in vivo, which may contribute to maintain their unique epigenetic memory. In this proposal, we plan to: (1) explore what mechanisms control asymmetric versus symmetric histone incorporation in Drosophila male germline; (2) study asymmetric histone inheritance and its biological functions in Drosophila neuroblast and intestinal stem cell systems; (3) develop a new method to identify genetic locus with epigenetic signature. We anticipate that our studies will lead to (1) a series of findings to resolve fundamental questions in biology and yield new insights in explaining cell fate determination in multicellular organisms, (2) the development of new tools that will benefit the broader scientific community, and (3) insight on therapeutic strategies against various diseases, such as degenerative disease and many forms of cancer, due to mis-regulated cell fate determination.


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 = $399,556 )
2026	2026	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	8	5/5/2026	NON-COMPETING CONTINUATION	$399,556
														Subtotal = $399,556

Issue Date FY: 2025 ( Subtotal = $399,556 )
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	002	7	4/28/2025	NON-COMPETING CONTINUATION	$399,556
2025	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	6	11/4/2024	COMPETING CONTINUATION	$0
2025	2022	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	001	5	2/10/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $399,556

Issue Date FY: 2024 ( Subtotal = $399,556 )
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	6	6/27/2024	COMPETING CONTINUATION	$399,556
														Subtotal = $399,556

Issue Date FY: 2022 ( Subtotal = $329,665 )
2022	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	5	4/29/2022	NON-COMPETING CONTINUATION	$320,287
2022	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	001	5	5/2/2022	SUPPLEMENT FOR EXPANSION	$9,378
														Subtotal = $329,665

Issue Date FY: 2021 ( Subtotal = $432,813 )
2021	2021	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	4	4/30/2021	NON-COMPETING CONTINUATION	$432,813
														Subtotal = $432,813

Issue Date FY: 2020 ( Subtotal = $452,029 )
2020	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	002	3	6/11/2020	SUPPLEMENT FOR EXPANSION	$103,149
2020	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	003	3	7/20/2020	SUPPLEMENT FOR EXPANSION	$8,555
2020	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	001	3	6/2/2020	SUPPLEMENT FOR EXPANSION	$11,430
2020	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	3	5/5/2020	NON-COMPETING CONTINUATION	$328,895
														Subtotal = $452,029

Issue Date FY: 2019 ( Subtotal = $439,459 )
2019	2019	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	2	4/26/2019	NON-COMPETING CONTINUATION	$423,577
2019	2019	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	001	2	9/18/2019	SUPPLEMENT FOR EXPANSION	$15,882
														Subtotal = $439,459

Issue Date FY: 2018 ( Subtotal = $368,059 )
2018	2018	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	1	3/30/2018	NEW	$273,389
2018	2018	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	001	1	6/26/2018	SUPPLEMENT FOR EXPANSION	$94,670
														Subtotal = $368,059

Grand Total All Awards = $3,220,693

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Study epigenetic inheritance during development, homeostasis and regeneration

Award Number: R35GM127075

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2018

PERIOD OF PERFORMANCE END DATE: 04/30/2029

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