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Anti-Coagulation Factors and Placentation

Award Number: R01HD099638
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: 07/17/2019
PERIOD OF PERFORMANCE END DATE: 05/31/2024

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Anti-Coagulation Factors and Placentation - 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. Central to the vascular remodeling process is a specialized population of trophoblast cells referred to as invasive trophoblast cells and in the human, extravillous trophoblast. These cells migrate from the placenta into the uterus where they contribute to the restructuring of the uterine spiral arteries, which facilitate the delivery of nutrients to the placenta and fetus. Disruptions in this fundamental process lead to diseases of pregnancy and placentation, including the “Great Obstetrical Syndromes” (preeclampsia, intrauterine growth restriction, preterm birth, abruptio placentae). Many of these disorders are associated with coagulopathies. In this research proposal we investigate roles for two anti-coagulation factors, tissue factor pathway inhibitor (TFPI) and thrombomodulin (THBD), as a regulators of invasive trophoblast lineage development and uterine spiral artery remodeling. Our proposed research uses the rat as an experimental model because it exhibits deep intrauterine trophoblast invasion and extensive uterine spiral artery remodeling similar to human placentation. We will utilize rat and human trophoblast stem cells to evaluate molecular mechanisms involved in differentiation of the invasive trophoblast lineage. Hypotheses for the conserved involvement of TFPI and THBD in placentation will be tested in vivo using rat models created by genome editing and through lentiviral-mediated trophectoderm gene manipulation. This study will facilitate elucidation of molecular pathways controlling the invasive trophoblast cell lineage and uterine spiral artery remodeling and create a platform for understanding the pathogenesis of diseases impacting placentation.


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: 2024 ( Subtotal = -$9,848 )
2024	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	000	5	9/24/2024	NON-COMPETING CONTINUATION	-$9,848
														Subtotal = -$9,848

Issue Date FY: 2023 ( Subtotal = $496,687 )
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	000	5	5/17/2023	NON-COMPETING CONTINUATION	$496,687
														Subtotal = $496,687

Issue Date FY: 2022 ( Subtotal = $496,687 )
2022	2022	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	4	5/31/2022	NON-COMPETING CONTINUATION	$496,687
														Subtotal = $496,687

Issue Date FY: 2021 ( Subtotal = $496,687 )
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	3	5/10/2021	NON-COMPETING CONTINUATION	$496,687
														Subtotal = $496,687

Issue Date FY: 2020 ( Subtotal = $506,824 )
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	2	5/14/2020	NON-COMPETING CONTINUATION	$506,824
														Subtotal = $506,824

Issue Date FY: 2019 ( Subtotal = $520,074 )
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	1	7/16/2019	NEW	$520,074
														Subtotal = $520,074

Grand Total All Awards = $2,507,111

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Anti-Coagulation Factors and Placentation

Award Number: R01HD099638

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: 07/17/2019

PERIOD OF PERFORMANCE END DATE: 05/31/2024

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