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GATA Factor Function in Trophoblast

Award Number: R01HD062546
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/16/2010
PERIOD OF PERFORMANCE END DATE: 03/31/2030

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GATA Factor Function in Trophoblast - Abstract Rodent and Human pregnancies are associated with a hemochorial placentation. Central to the hemochorial placentation are two trophoblast cell types; (i) syncytiotrophoblasts (STBs), which establish an exchange surface for nutrients and gases at the maternal-fetal interface, and (ii) a specialized population of trophoblast cells referred to as invasive trophoblasts in rodents and extravillous trophoblasts (EVTs), in human. Invasive Trophoblasts/EVTs invade into the maternal uterine tissue and modulate uterine cells, including immune cells and endothelial cells to support continuation of pregnancy and proper development of the fetus. Defective development and function of EVTs contribute to early pregnancy loss and pregnancy associated complications such as preeclampsia and intrauterine growth restriction. Our published and unpublished preliminary studies have established that GATA family transcription factors, GATA2 and GATA3, are conserved in trophoblast cells, including in invasive trophoblasts, across mammalian species and are critical regulators for mammalian placentation. The overarching goal of this proposal is to further define GATA factor-mediated transcriptional mechanisms that regulate development and proper function of specialized trophoblast cell types at the maternal-fetal interface and how defects in GATA factor function contribute to pathological pregnancies. Two specific aims are proposed. In Aim 1, We will study mutant rats, and mutant human TSCs, in which GATA2 and GATA3 will be conditionally deleted and utilize state-of-the art genomics approaches to test the hypothesis that GATA2/GATA3 establish conserved transcriptional program to regulate development and function of invasive trophoblast/EVT lineage. In Aim 2, we will test the hypothesis that defective GATA3 function in trophoblast cells contributes to defective placentation in Trisomy 21 pregnancies. We will study placental tissues from chorionic villous biopsies, patient-specific human trophoblast stem cells and mouse models, representing human Trisomy 21, to test this hypothesis. Successful completion of proposed research will advance our knowledge about GATA factor- mediated molecular mechanisms regulating development and function of the invasive trophoblast/EVT cell lineage and whether impairment of those mechanisms could contribute to pathological pregnancies, such as Trisomy 21.


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: 2025 ( Subtotal = $572,161 )
2025	2025	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	3901 RAINBOW BLVD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Child Health and Human Development Extramural Research	000	11	6/13/2025	COMPETING CONTINUATION	$572,161
														Subtotal = $572,161

Issue Date FY: 2024 ( Subtotal = -$7,894 )
2024	2021	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	3901 RAINBOW BLVD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Child Health and Human Development Extramural Research	000	10	8/27/2024	NON-COMPETING CONTINUATION	-$7,894
														Subtotal = -$7,894

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	3901 RAINBOW BLVD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Child Health and Human Development Extramural Research	000	10	4/5/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $438,990 )
2021	2021	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	4330 SHAWNEE MISSION PKWY	SHAWNEE MISSION	KS	66205	JOHNSON	USA	Child Health and Human Development Extramural Research	000	10	4/21/2021	NON-COMPETING CONTINUATION	$438,990
														Subtotal = $438,990

Issue Date FY: 2020 ( Subtotal = $447,950 )
2020	2020	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	4330 SHAWNEE MISSION PKWY	SHAWNEE MISSION	KS	66205	JOHNSON	USA	Child Health and Human Development Extramural Research	000	9	4/30/2020	NON-COMPETING CONTINUATION	$447,950
														Subtotal = $447,950

Issue Date FY: 2019 ( Subtotal = $447,950 )
2019	2019	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	4330 SHAWNEE MISSION PKWY	SHAWNEE MISSION	KS	66205	JOHNSON	USA	Child Health and Human Development Extramural Research	000	8	5/23/2019	NON-COMPETING CONTINUATION	$447,950
														Subtotal = $447,950

Issue Date FY: 2018 ( Subtotal = $447,950 )
2018	2018	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	4330 SHAWNEE MISSION PKWY	SHAWNEE MISSION	KS	66205	JOHNSON	USA	Child Health and Human Development Extramural Research	000	7	5/16/2018	NON-COMPETING CONTINUATION	$447,950
														Subtotal = $447,950

Issue Date FY: 2017 ( Subtotal = $496,216 )
2017	2017	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	4330 SHAWNEE MISSION PKWY	SHAWNEE MISSION	KS	66205	JOHNSON	USA	Child Health and Human Development Extramural Research	000	6	8/1/2017	COMPETING CONTINUATION	$496,216
														Subtotal = $496,216

Issue Date FY: 2014 ( Subtotal = $297,432 )
2014	2014	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Child Health and Human Development Extramural Research	000	5	5/5/2014	NON-COMPETING CONTINUATION	$297,432
														Subtotal = $297,432

Issue Date FY: 2013 ( Subtotal = $290,394 )
2013	2013	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Child Health and Human Development Extramural Research	000	4	6/11/2013	NON-COMPETING CONTINUATION	$290,394
														Subtotal = $290,394

Issue Date FY: 2012 ( Subtotal = $306,000 )
2012	2012	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Child Health and Human Development Extramural Research	000	3	6/4/2012	NON-COMPETING CONTINUATION	$306,000
														Subtotal = $306,000

Issue Date FY: 2011 ( Subtotal = $306,000 )
2011	2011	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Child Health and Human Development Extramural Research	000	2	6/10/2011	NON-COMPETING CONTINUATION	$306,000
														Subtotal = $306,000

Issue Date FY: 2010 ( Subtotal = $318,750 )
2010	2010	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Child Health and Human Development Extramural Research	000	1	8/11/2010	NEW	$318,750
														Subtotal = $318,750

Grand Total All Awards = $4,361,899

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GATA Factor Function in Trophoblast

Award Number: R01HD062546

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/16/2010

PERIOD OF PERFORMANCE END DATE: 03/31/2030

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