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Regulators of the Erythroid Terminal Differentiation Decision and their Connection to the Cell Cycle

Award Number: F30DK107182
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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¿ DESCRIPTION (provided by applicant): BFUe, the most primitive committed erythroid progenitors, are capable of extensive proliferation. BFUe differentiate into CFUe, cells with very restricted proliferative potential. Pu.1 is a hematopoietic, master regulatory ETS transcription factor (TF) that is required for BFUe self-renewal. PU.1 inhibits BFUe differentiation. Down regulation of PU.1 occurs and is required for BFUe to differentiate into CFUe. Despite Pu.1's central role in regulating the terminal differentiation decision, the molecular mechanism controlling Pu.1's expression and down-regulation are not known. We propose to identify the cis-regulatory elements that control Pu.1 expression in BFUe and it's down regulation as these progenitors enter terminal differentiation. Using computational analysis of gene expression, ChIP Seq and other types of genome-wide data sets, we have identified several DNA binding proteins as candidates for controlling Pu.1 expression in BFUe, including SATB1, E2F4, Runx and Jun. The analysis also suggests that some of these factors, Runx and Jun, collaborate with Pu.1 to regulate a large set of genes that promote proliferation of BFUe and antagonize their terminal differentiation. We propose to determine whether these factors regulate Pu.1 expression. We also propose to determine whether they work in concert with Pu.1 to control a set of important gene targets in erythroid cells. The successful completion of this work will provide essential insights into the transcriptional networks that regulate red blood cell output.


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: 2021 ( Subtotal = $0 )
2021	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	12/28/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	2/7/2019	NON-COMPETING CONTINUATION	-$20,985
2019	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	6	2/7/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$20,985
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $53,573 )
2018	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	7/2/2018	NON-COMPETING CONTINUATION	$49,524
2018	2015	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	10/31/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$4,049
														Subtotal = $53,573

Issue Date FY: 2017 ( Subtotal = $49,044 )
2017	2017	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	6/30/2017	NON-COMPETING CONTINUATION	$49,044
														Subtotal = $49,044

Issue Date FY: 2016 ( Subtotal = $48,576 )
2016	2016	ALBERT EINSTEIN COLLEGE OF MEDICINE INC	111 E 210TH ST	BRONX	NY	10467	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	7/19/2016	NON-COMPETING CONTINUATION	$48,576
														Subtotal = $48,576

Issue Date FY: 2015 ( Subtotal = $48,120 )
2015	2015	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	6/29/2015	NEW	$48,120
2015	2015	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	1	9/17/2015	NEW	-$40,100
2015	2015	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	6/29/2015	NEW	$0
2015	2015	ALBERT EINSTEIN COLLEGE OF MEDICINE INC	111 E 210TH ST	BRONX	NY	10467	BRONX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	2	9/17/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$40,100
														Subtotal = $48,120

Grand Total All Awards = $199,313

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Regulators of the Erythroid Terminal Differentiation Decision and their Connection to the Cell Cycle

Award Number: F30DK107182

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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