Wednesday, February 5, 2025 2/5/2025

Trophoblast Differentiation

Award Number: R01HD020676
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY/ABSTRACT Hemochorial placentation occurs in many mammalian species including primates and rodents. It ensures the most intimate contact between maternal and embryonic compartments and requires specialized adjustments. Among these adjustments is the need for extensive remodeling of the maternal uterine spiral arteries. Uterine vascular modifications are required for the delivery of nutrients to the fetus. Mechanisms controlling uterine spiral artery remodeling remain poorly understood. Central to the vascular remodeling process is a specialized population of trophoblast cells referred to as invasive trophoblast cells (generic term) or alternatively as extravillous trophoblast (EVT) cells (human-specific term). Impairments in differentiation of the invasive trophoblast/EVT cell lineage, intrauterine trophoblast cell invasion, and/or trophoblast cell-directed uterine cell modulation contribute to early pregnancy loss, placental dysfunction, pregnancy-related diseases, and a range of postnatal health issues. Our long-term goal is to elucidate regulatory processes controlling development of the invasive trophoblast/EVT cell lineage and their role in establishing the uterine-placental interface. Placentation in the human and rat are both characterized by deep intrauterine trophoblast cell invasion and extensive trophoblast cell guided spiral artery remodeling. Our research strategy is based on our prior establishment and extensive characterization of in vitro and in vivo models for studying deep hemochorial placentation in the rat and the utilization of human placentation site specimens and human trophoblast stem cells for investigating gene regulatory networks controlling EVT cell development. In this proposal we focus on two regulatory pathways controlling invasive trophoblast/EVT cell differentiation: i) phosphatidylinositol 3- kinase (PI3K)/AKT pathway; ii) CBP/EP300-interacting transactivator with Glu/Asp rich carboxy-terminal domain 2 (CITED2)-regulated pathway. These regulatory pathways are viewed as entry points and guides to mechanisms controlling development of the invasive trophoblast/EVT cell lineage. The proposed research provides an innovative approach to studying deep hemochorial placentation. Collectively, the research is directed toward elucidating molecular mechanisms underlying physiologically relevant processes that ensure successful hemochorial placentation. This approach will lead to the identification of conserved regulatory pathways controlling the invasive trophoblast/EVT cell lineage, which will create opportunities and a platform for understanding the pathogenesis of placental anomalies leading to pregnancy 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: 2025 ( Subtotal = $507,228 )
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	36	12/19/2024	NON-COMPETING CONTINUATION	$507,228
2025	2023	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	3901 RAINBOW BLVD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Child Health and Human Development Extramural Research	002	34	1/29/2025	COMPETING CONTINUATION	$1,420
2025	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	001	33	1/29/2025	NON-COMPETING CONTINUATION	-$1,420
														Subtotal = $507,228

Issue Date FY: 2024 ( Subtotal = $563,378 )
2024	2024	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	35	12/26/2023	NON-COMPETING CONTINUATION	$512,163
2024	2024	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	3901 RAINBOW BLVD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Child Health and Human Development Extramural Research	001	35	5/1/2024	NON-COMPETING CONTINUATION	$51,215
														Subtotal = $563,378

Issue Date FY: 2023 ( Subtotal = $571,854 )
2023	2023	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE, INC.	3901 RAINBOW BLVD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Child Health and Human Development Extramural Research	001	34	3/3/2023	COMPETING CONTINUATION	$571,854
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	33	2/23/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $571,854

Issue Date FY: 2021 ( Subtotal = $462,534 )
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	33	4/12/2021	NON-COMPETING CONTINUATION	$462,534
														Subtotal = $462,534

Issue Date FY: 2020 ( Subtotal = $471,973 )
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	32	4/30/2020	NON-COMPETING CONTINUATION	$471,973
														Subtotal = $471,973

Issue Date FY: 2019 ( Subtotal = $471,973 )
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	31	4/25/2019	NON-COMPETING CONTINUATION	$471,973
														Subtotal = $471,973

Issue Date FY: 2018 ( Subtotal = $471,973 )
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	30	5/23/2018	NON-COMPETING CONTINUATION	$471,973
														Subtotal = $471,973

Issue Date FY: 2017 ( Subtotal = $471,973 )
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	002	29	9/26/2017	COMPETING CONTINUATION	$52,496
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	29	4/24/2017	COMPETING CONTINUATION	$471,973
2017	2016	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	001	28	9/26/2017	EXTENSION WITH OR WITHOUT FUNDS	-$52,496
														Subtotal = $471,973

Issue Date FY: 2016 ( Subtotal = $394,163 )
2016	2016	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Child Health and Human Development Extramural Research	000	28	4/22/2016	EXTENSION WITH OR WITHOUT FUNDS	$394,163
														Subtotal = $394,163

Issue Date FY: 2015 ( Subtotal = $385,221 )
2015	2015	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Child Health and Human Development Extramural Research	000	27	4/7/2015	NON-COMPETING CONTINUATION	$385,221
														Subtotal = $385,221

Issue Date FY: 2014 ( Subtotal = $381,168 )
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	26	4/29/2014	NON-COMPETING CONTINUATION	$381,168
														Subtotal = $381,168

Issue Date FY: 2013 ( Subtotal = $369,422 )
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	001	25	5/20/2013	NON-COMPETING CONTINUATION	$19,073
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	25	5/1/2013	NON-COMPETING CONTINUATION	$350,349
														Subtotal = $369,422

Issue Date FY: 2012 ( Subtotal = $386,492 )
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	001	24	7/13/2012	COMPETING CONTINUATION	$383,933
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	002	24	7/17/2012	COMPETING CONTINUATION	$2,559
2012	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	23	7/6/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $386,492

Issue Date FY: 2011 ( Subtotal = $284,098 )
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	23	6/3/2011	NON-COMPETING CONTINUATION	$284,098
														Subtotal = $284,098

Issue Date FY: 2010 ( Subtotal = $295,936 )
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	22	4/27/2010	NON-COMPETING CONTINUATION	$295,936
														Subtotal = $295,936

Issue Date FY: 2009 ( Subtotal = $298,925 )
2009	2009	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Child Health and Human Development Extramural Research	000	21	5/7/2009	NON-COMPETING CONTINUATION	$298,925
														Subtotal = $298,925

Issue Date FY: 2008 ( Subtotal = $318,613 )
2008	2008	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Child Health and Human Development Extramural Research	000	20	4/16/2008	NON-COMPETING CONTINUATION	$298,925
2008	2008	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Child Health and Human Development Extramural Research	001	20	8/21/2008	SUPPLEMENT FOR EXPANSION	$19,688
														Subtotal = $318,613

Issue Date FY: 2007 ( Subtotal = $305,025 )
2007	2007	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Child Health and Human Development Extramural Research	000	19	5/7/2007	COMPETING CONTINUATION	$305,025
														Subtotal = $305,025

Issue Date FY: 2006 ( Subtotal = $363,991 )
2006	2006	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Child Health and Human Development Extramural Research	000	18	5/25/2006	NON-COMPETING CONTINUATION	$363,991
														Subtotal = $363,991

Issue Date FY: 2005 ( Subtotal = $372,750 )
2005	2005	UNIVERSITY OF KANSAS, MEDICAL CENTER	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Child Health and Human Development Extramural Research	000	16	3/30/2005	NON-COMPETING CONTINUATION	$372,750
														Subtotal = $372,750

Grand Total All Awards = $9,940,733

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Trophoblast Differentiation

Award Number: R01HD020676

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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