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Function of Putative Determinant in Hematopoiesis

Award Number: R01DK046865
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/1993
PERIOD OF PERFORMANCE END DATE: 01/31/2030

Group Awards By:

View Award Description

Function of Putative Determinant in Hematopoiesis - SUMMARY Cell-restricted transcriptional modulators play critical roles in the process of selective gene regulation during hematopoiesis. We have been investigating the molecular and biological function of Erythroid Krüppel-like Factor (EKLF; KLF1). EKLF is a cell-restricted transcription factor that is a global regulator of genes essential for the erythroid program. This proposal describes experiments that build on unanticipated novel observations made during the previous funding cycle that extend this long-term study towards innovative directions: We have shown that EKLF is an integrator of transcriptional and epigenetic inputs for gene activation. The experiments of Aim 1 will assess the consequences of its acute depletion and will determine the biochemical order by which EKLF re-establishes the properly formed active locus. We found that EKLF/KLF1 can associate in vivo with repressor proteins in addition to co- activators. The experiments of Aim 2 will use the congenital dyserythropoietic anemia (CDA type IV; KLF1(E325K)) model to assess the regulatory importance of these varied interactions. We find a remarkable association between male CDA type IV patients and disorders of sexual development (DSD). The experiments of Aim 3 will test a model that follows from the neomophic expression pattern uniquely seen in patient cells. The studies will be aided by the use of molecular, biochemical, cellular, and genetic approaches, by taking advantage of the heightened sensitivity affordable by recent technological advances, and by novel mouse strains and human patient derived pluripotent lines that have been newly established. As a result, all analyses will use primary or minimally manipulated cells. Elucidating EKLF’s role in regulatory phenomena will continue to illuminate novel aspects of the essential mechanisms by which a cell-restricted transcription factor can exert varied yet highly controlled influences on genetic expression, epigenetics, and distal systemic effects.


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: 2027 ( Subtotal = $0 )
2027	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	31	10/22/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2026 ( Subtotal = $642,909 )
2026	2026	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	32	5/19/2026	COMPETING CONTINUATION	$642,909
2026	2026	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	32	6/11/2026	COMPETING CONTINUATION	$0
2026	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	31	5/15/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $642,909

Issue Date FY: 2024 ( Subtotal = $510,203 )
2024	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	31	7/24/2024	NON-COMPETING CONTINUATION	$510,203
														Subtotal = $510,203

Issue Date FY: 2023 ( Subtotal = $642,939 )
2023	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	30	6/28/2023	NON-COMPETING CONTINUATION	$642,939
														Subtotal = $642,939

Issue Date FY: 2022 ( Subtotal = $642,939 )
2022	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	29	8/10/2022	NON-COMPETING CONTINUATION	$642,939
2022	2021	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	28	3/21/2022	COMPETING CONTINUATION	$168,991
2022	2020	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	27	3/21/2022	NON-COMPETING CONTINUATION	-$168,991
														Subtotal = $642,939

Issue Date FY: 2021 ( Subtotal = $622,346 )
2021	2021	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	28	7/23/2021	COMPETING CONTINUATION	$622,346
2021	2020	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	27	7/15/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $622,346

Issue Date FY: 2020 ( Subtotal = $650,688 )
2020	2020	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	27	3/27/2020	NON-COMPETING CONTINUATION	$650,688
														Subtotal = $650,688

Issue Date FY: 2019 ( Subtotal = $650,688 )
2019	2019	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	26	9/21/2019	SUPPLEMENT FOR EXPANSION	$149,229
2019	2019	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	26	3/20/2019	NON-COMPETING CONTINUATION	$501,459
														Subtotal = $650,688

Issue Date FY: 2018 ( Subtotal = $501,459 )
2018	2018	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	25	5/2/2018	NON-COMPETING CONTINUATION	$501,459
														Subtotal = $501,459

Issue Date FY: 2017 ( Subtotal = $519,459 )
2017	2017	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	24	4/21/2017	COMPETING CONTINUATION	$519,459
2017	2017	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	24	8/15/2017	COMPETING CONTINUATION	$10,733
2017	2015	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	23	4/18/2017	NON-COMPETING CONTINUATION	$0
2017	2015	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	23	8/15/2017	NON-COMPETING CONTINUATION	-$10,733
														Subtotal = $519,459

Issue Date FY: 2015 ( Subtotal = $481,453 )
2015	2015	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL, BOX 3500	NEW YORK-NEW YORK	NY	10029		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	23	7/28/2015	NON-COMPETING CONTINUATION	$481,453
														Subtotal = $481,453

Issue Date FY: 2014 ( Subtotal = $492,513 )
2014	2014	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL, BOX 3500	NEW YORK-NEW YORK	NY	10029		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	22	8/21/2014	NON-COMPETING CONTINUATION	$492,513
														Subtotal = $492,513

Issue Date FY: 2013 ( Subtotal = $475,275 )
2013	2013	MT SINAI SCHOOL OF MEDICINE	1 GUSTAVE L LEVY PL, BOX 3500	NEW YORK-NEW YORK	NY	10029		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	21	7/30/2013	NON-COMPETING CONTINUATION	$475,275
														Subtotal = $475,275

Issue Date FY: 2012 ( Subtotal = $498,853 )
2012	2012	MT SINAI SCHOOL OF MEDICINE	1 GUSTAVE L LEVY PL, BOX 3500	NEW YORK-NEW YORK	NY	10029		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	20	7/19/2012	COMPETING CONTINUATION	$498,853
2012	2011	MT SINAI SCHOOL OF MEDICINE	1 GUSTAVE L LEVY PL, BOX 3500	NEW YORK-NEW YORK	NY	10029		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	19	7/17/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $498,853

Issue Date FY: 2011 ( Subtotal = $348,286 )
2011	2011	MT SINAI SCHOOL OF MEDICINE	1 GUSTAVE L LEVY PL, BOX 3500	NEW YORK-NEW YORK	NY	10029		USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	19	6/10/2011	NON-COMPETING CONTINUATION	$348,286
														Subtotal = $348,286

Issue Date FY: 2010 ( Subtotal = $351,804 )
2010	2010	MT SINAI SCHOOL OF MEDICINE	1 GUSTAVE L LEVY PL, BOX 3500	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	18	5/17/2010	NON-COMPETING CONTINUATION	$351,804
														Subtotal = $351,804

Issue Date FY: 2009 ( Subtotal = $355,359 )
2009	2009	MT SINAI SCHOOL OF MEDICINE	1 GUSTAVE L LEVY PL, BOX 3500	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	17	6/5/2009	NON-COMPETING CONTINUATION	$355,359
														Subtotal = $355,359

Issue Date FY: 2008 ( Subtotal = $340,591 )
2008	2008	MT SINAI SCHOOL OF MEDICINE	1 GUSTAVE L LEVY PL, BOX 3500	NEW YORK-NEW YORK	NY	10029		USA	Kidney Diseases, Urology and Hematology Research	000	16	6/3/2008	COMPETING CONTINUATION	$340,591
														Subtotal = $340,591

Issue Date FY: 2007 ( Subtotal = $318,219 )
2007	2007	MT SINAI SCHOOL OF MEDICINE	1 GUSTAVE L LEVY PL, BOX 3500	NEW YORK-NEW YORK	NY	10029		USA	Kidney Diseases, Urology and Hematology Research	000	15	6/5/2007	NON-COMPETING CONTINUATION	$318,219
														Subtotal = $318,219

Issue Date FY: 2006 ( Subtotal = $327,723 )
2006	2006	MT SINAI SCHOOL OF MEDICINE	1 GUSTAVE L LEVY PL, BOX 3500	NEW YORK-NEW YORK	NY	10029		USA	Kidney Diseases, Urology and Hematology Research	000	14	6/5/2006	NON-COMPETING CONTINUATION	$327,723
														Subtotal = $327,723

Grand Total All Awards = $11,645,855

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Function of Putative Determinant in Hematopoiesis

Award Number: R01DK046865

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/1993

PERIOD OF PERFORMANCE END DATE: 01/31/2030

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