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STAT5 Structure-Function in Hematopoiesis

Award Number: R01DK059380
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: 03/01/2002
PERIOD OF PERFORMANCE END DATE: 07/31/2012

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STAT5 Structure-Function in Hematopoiesis - DESCRIPTION (provided by applicant): Our lab has been studying the role of signal transducer and activator of transcription 5 (STAT5) in hematopoiesis for more than a decade and we have identified important roles in hematopoietic and immune cell biology. Despite these advances in understanding the severity and broad range of defects in mice lacking STAT5, the mechanisms by which STAT5-mediated transcriptional activation controls hematopoiesis are not fully defined. We recently reported that although STAT5 drives multilineage differentiation it plays a surprising role in promoting hematopoietic stem cell quiescence. We have already identified key target genes involved in this process, including tie2 and p57. There are big differences between the hematopoietic stem cell and progenitor niches in regard to their oxidation potential and STAT5 is sensitive to reactive oxygen and nitrogen species. We will explore the overall hypothesis that STAT5-mediated transcriptional activation in the hypoxic hematopoietic stem cell niche is unique from that in the oxidation promoting hematopoietic progenitor niche and that changes in STAT5 function depend on the microenvironment and can control engraftment, mobilization, lineage differentiation, and quiescence. We have already performed preliminary gene expression array analysis of STAT5-deficient c-Kit+Sca-1+Lin- (KLS) cells and have utilized chromatin immunoprecipitation assays that identified bcl2 as a novel STAT5 direct target gene. Therefore we will test the following aims: 1) We will use a novel viable hematopoietic-specific conditional knockout mouse to study how STAT5 modulates juvenile seeding of the niches, migration, and mobilization. 2) We have demonstrated that the long-term repopulating hematopoietic stem cell pool is uniquely sensitive to STAT5 deletion, whereas the short-term repopulating pool is spared. We will analyze lineage differentiation in STAT5-deficient mice and characterize lymphoid priming and predisposition to B-lineage acute lymphoblastic leukemia. 3) We will perform STAT5 ChIP-qPCR experiments in multipotent hematopoietic cells and identify mechanisms of redox regulation. Collectively, these three aims will provide important insight into the functional and molecular regulation of hematopoiesis by STAT5 in response to early acting cytokines and may lead to improved therapeutic approaches for treating blood disorders.


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: 2020 ( Subtotal = -$1 )
2020	2017	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	15	9/17/2020	NON-COMPETING CONTINUATION	-$1
														Subtotal = -$1

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2017	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	15	1/23/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $339,300 )
2017	2017	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	15	6/15/2017	NON-COMPETING CONTINUATION	$33,930
2017	2017	EMORY UNIVERSITY	1599 CLIFTON RD.	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	15	3/28/2017	NON-COMPETING CONTINUATION	$305,370
														Subtotal = $339,300

Issue Date FY: 2016 ( Subtotal = $339,300 )
2016	2016	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	14	4/6/2016	EXTENSION WITH OR WITHOUT FUNDS	$339,300
														Subtotal = $339,300

Issue Date FY: 2015 ( Subtotal = $339,300 )
2015	2015	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	13	4/3/2015	NON-COMPETING CONTINUATION	$339,300
														Subtotal = $339,300

Issue Date FY: 2014 ( Subtotal = $339,300 )
2014	2014	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	12	2/25/2014	NON-COMPETING CONTINUATION	$339,300
														Subtotal = $339,300

Issue Date FY: 2013 ( Subtotal = $339,300 )
2013	2013	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	11	3/11/2013	COMPETING CONTINUATION	$339,300
2013	2011	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	10	3/7/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $339,300

Issue Date FY: 2011 ( Subtotal = $290,540 )
2011	2011	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	10	9/7/2011	NON-COMPETING CONTINUATION	$290,540
														Subtotal = $290,540

Issue Date FY: 2010 ( Subtotal = $293,474 )
2010	2010	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	9	8/24/2010	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$293,474
2010	2010	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	9	8/18/2010	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$293,474
2010	2010	EMORY UNIVERSITY	1784 N DECATUR RD,S 530 NDBLDG	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	8/16/2010	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$293,474
2010	2009	CASE WESTERN RESERVE UNIVERSITY	2040 ADELBERT ROAD	CLEVELAND	OH	44106	CUYAHOGA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	8	8/16/2010	NON-COMPETING CONTINUATION	$0
														Subtotal = $293,474

Issue Date FY: 2009 ( Subtotal = $400,256 )
2009	2009	CASE WESTERN RESERVE UNIVERSITY	2040 ADELBERT ROAD	CLEVELAND	OH	44106	CUYAHOGA	USA	Trans-NIH Recovery Act Research Support	000	7	9/23/2009	SUPPLEMENT FOR EXPANSION	$99,993
2009	2009	CASE WESTERN RESERVE UNIVERSITY	2040 ADELBERT ROAD	CLEVELAND	OH	44106	CUYAHOGA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	8	6/29/2009	NON-COMPETING CONTINUATION	$300,263
														Subtotal = $400,256

Issue Date FY: 2008 ( Subtotal = $300,263 )
2008	2008	CASE WESTERN RESERVE UNIVERSITY	2040 ADELBERT ROAD	CLEVELAND	OH	44106	CUYAHOGA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	7	3/17/2008	COMPETING CONTINUATION	$300,263
														Subtotal = $300,263

Issue Date FY: 2006 ( Subtotal = $245,023 )
2006	2006	CASE WESTERN RESERVE UNIVERSITY	2040 ADELBERT ROAD	CLEVELAND	OH	44106	CUYAHOGA	USA	Kidney Diseases, Urology and Hematology Research	000	6	1/18/2006	NON-COMPETING CONTINUATION	$245,023
														Subtotal = $245,023

Issue Date FY: 2005 ( Subtotal = $250,920 )
2005	2005	CASE WESTERN RESERVE UNIVERSITY	2040 ADELBERT ROAD	CLEVELAND	OH	44106	CUYAHOGA	USA	Kidney Diseases, Urology and Hematology Research	000	5	12/27/2004	NON-COMPETING CONTINUATION	$250,920
														Subtotal = $250,920

Issue Date FY: 2004 ( Subtotal = $252,888 )
2004	2004	CASE WESTERN RESERVE UNIVERSITY	2040 ADELBERT ROAD	CLEVELAND	OH	44106	CUYAHOGA	USA	Kidney Diseases, Urology and Hematology Research	000	4	7/19/2004	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$245,224
2004	2004	AMERICAN NATIONAL RED CROSS HEADQUARTERS	600 A FOREST POINT CIRCLE	CHARLOTTE	NC	28273	MECKLENBURG	USA	Kidney Diseases, Urology and Hematology Research	000	3	11/24/2003	NON-COMPETING CONTINUATION	$7,664
														Subtotal = $252,888

Issue Date FY: 2003 ( Subtotal = $252,888 )
2003	2003	AMERICAN NATIONAL RED CROSS HEADQUARTERS	600 A FOREST POINT CIRCLE	CHARLOTTE	NC	28273	MECKLENBURG	USA	Kidney Diseases, Urology and Hematology Research	000	2		NON-COMPETING CONTINUATION	$252,888
														Subtotal = $252,888

Issue Date FY: 2002 ( Subtotal = $252,888 )
2002	2002	AMERICAN NATIONAL RED CROSS HEADQUARTERS	600 A FOREST POINT CIRCLE	CHARLOTTE	NC	28273	MECKLENBURG	USA	Kidney Diseases, Urology and Hematology Research	000	1	1/31/2002	NEW	$252,888
														Subtotal = $252,888

Grand Total All Awards = $4,235,639

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STAT5 Structure-Function in Hematopoiesis

Award Number: R01DK059380

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: 03/01/2002

PERIOD OF PERFORMANCE END DATE: 07/31/2012

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