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Adrenomedullin Signaling at the Maternal-Fetal Interface

Award Number: R01HD060860
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: 04/01/2009
PERIOD OF PERFORMANCE END DATE: 01/31/2028

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Adrenomedullin Signaling at the Maternal-Fetal Interface - Project Abstract Adrenomedullin (AM) is a multifunctional peptide that is involved in a variety of biological processes, including embryonic development, angiogenesis, cardio-protection, and innate immunity. Maternal plasma levels of AM rise substantially during a normal pregnancy, but abnormally low levels are often associated with a variety of pregnancy complications including preeclampsia, fetal growth restriction, gestational diabetes and spontaneous abortion. Using genetically engineered mouse models, our laboratory was the first to demonstrate that haploinsufficiency for maternal AM causes a multitude of reproductive defects associated with abnormal implantation and fetal growth restriction. More recently, we extended these findings to humans by identifying the first loss-of-function mutation in the AM G protein-coupled receptor CALCRL, associated with hydrops fetalis, placental edema and maternal subfertility. Collectively our prior studies have defined the ways in which dosage of AM peptide and receptors can impact reproductive success, in animal models and in humans. Therefore, in this competitive renewal we are uniquely positioned to extend on our previous work by asking the overarching “bench-to- bedside” question of How does AM signaling affect its target cells during implantation and placentation and whether extrinsic factors can alter levels of AM to exert physiological effects on pregnancy outcomes? The focus of our studies places AM signaling as a cornerstone for elucidating fundamental questions related to pinopode formation (Aim 1), growth and remodeling of placental/decidual vasculature (Aim 2) and the roles of extrinsic environmental factors on reproductive outcomes (Aim 3). Using sophisticated genetic mouse models and in vitro pharmacological and cell biological assays, we intend to further our basic understanding of molecules and processes that govern maternal-to-fetal communication in the placenta and have the potential of providing new clinical therapeutic targets for the amelioration of complications of pregnancy.


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: 2026 ( Subtotal = $377,150 )
2026	2026	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	000	14	1/7/2026	NON-COMPETING CONTINUATION	$377,150
														Subtotal = $377,150

Issue Date FY: 2025 ( Subtotal = $419,055 )
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	000	13	1/13/2025	NON-COMPETING CONTINUATION	$377,150
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	001	13	4/14/2025	NON-COMPETING CONTINUATION	$41,905
														Subtotal = $419,055

Issue Date FY: 2024 ( Subtotal = $414,865 )
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	001	12	5/2/2024	NON-COMPETING CONTINUATION	$37,715
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	000	12	1/17/2024	NON-COMPETING CONTINUATION	$377,150
														Subtotal = $414,865

Issue Date FY: 2023 ( Subtotal = $419,055 )
2023	2023	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	000	11	4/13/2023	COMPETING CONTINUATION	$419,055
														Subtotal = $419,055

Issue Date FY: 2022 ( Subtotal = -$1 )
2022	2019	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	000	10	11/3/2021	NON-COMPETING CONTINUATION	-$1
														Subtotal = -$1

Issue Date FY: 2019 ( Subtotal = $310,847 )
2019	2019	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	000	10	8/8/2019	NON-COMPETING CONTINUATION	$310,847
														Subtotal = $310,847

Issue Date FY: 2018 ( Subtotal = $310,847 )
2018	2018	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	000	9	7/25/2018	NON-COMPETING CONTINUATION	$310,847
														Subtotal = $310,847

Issue Date FY: 2017 ( Subtotal = $310,847 )
2017	2017	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	000	8	7/31/2017	NON-COMPETING CONTINUATION	$310,847
														Subtotal = $310,847

Issue Date FY: 2016 ( Subtotal = $307,738 )
2016	2016	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	000	7	7/22/2016	NON-COMPETING CONTINUATION	$307,738
														Subtotal = $307,738

Issue Date FY: 2015 ( Subtotal = $310,847 )
2015	2015	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	000	6	9/25/2015	COMPETING CONTINUATION	$310,847
														Subtotal = $310,847

Issue Date FY: 2013 ( Subtotal = $275,366 )
2013	2013	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	000	5	4/2/2013	NON-COMPETING CONTINUATION	$261,148
2013	2013	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	001	5	6/10/2013	NON-COMPETING CONTINUATION	$14,218
														Subtotal = $275,366

Issue Date FY: 2012 ( Subtotal = $290,165 )
2012	2012	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	000	4	4/3/2012	NON-COMPETING CONTINUATION	$290,165
														Subtotal = $290,165

Issue Date FY: 2011 ( Subtotal = $290,165 )
2011	2011	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	001	3	3/11/2011	NON-COMPETING CONTINUATION	$272,030
2011	2011	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	002	3	7/12/2011	NON-COMPETING CONTINUATION	$18,135
2011	2009	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Trans-NIH Recovery Act Research Support	000	1	11/9/2010	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $290,165

Issue Date FY: 2010 ( Subtotal = $302,255 )
2010	2010	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Child Health and Human Development Extramural Research	000	2	3/29/2010	NON-COMPETING CONTINUATION	$302,255
														Subtotal = $302,255

Issue Date FY: 2009 ( Subtotal = $422,929 )
2009	2009	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Population Research	001	1	3/11/2009	NEW	$0
2009	2009	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Trans-NIH Recovery Act Research Support	002	1	9/22/2009	SUPPLEMENT FOR EXPANSION	$117,876
2009	2009	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Population Research	000	1	3/9/2009	NEW	$305,053
														Subtotal = $422,929

Grand Total All Awards = $4,762,130

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Adrenomedullin Signaling at the Maternal-Fetal Interface

Award Number: R01HD060860

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: 04/01/2009

PERIOD OF PERFORMANCE END DATE: 01/31/2028

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