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Role of OVO-like 1 in the regulation of human trophoblast differentiation

Award Number: R03HD079850
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: 09/23/2014
PERIOD OF PERFORMANCE END DATE: 03/31/2017

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Role of OVO-like 1 in the regulation of human trophoblast differentiation - ¿ DESCRIPTION (provided by applicant): Proper development of the placenta is paramount for fetal growth and viability. Maldevelopment of the placenta causes several complications of pregnancy, increasing the risk of morbidity and mortality for both mothers and newborn babies. A better understanding of the molecular networks that govern normal placental development will significantly improve our understanding of the pathogenesis of these pregnancy complications. Several specialized subtypes of trophoblast cells comprise the epithelial component of the placenta. One subtype - syncytiotrophoblast - is a unique, multinucleated lineage that forms the primary barrier between maternal and fetal circulations. Syncytiotrophoblast is continuously formed throughout pregnancy by cytoplasmic fusion of mononuclear cytotrophoblast cells. Fusion is a complex process catalyzed by human endogenous retrovirus-derived syncytin genes. Our primary objective is to define transcriptional networks that regulate the expression of syncytin genes and syncytiotrophoblast formation. Through microarray analysis, we are the first to identify that the conserved transcription factor OVOL1 is highly induced in a model of human syncytiotrophoblast formation. OVOL1 has been implicated in the regulation of epithelial differentiation in many species; however, its role in human trophoblast differentiation is not known. In preliminary analyses, we observed that depletion of OVOL1 has intriguing effects on the differentiation capacity of trophoblast cells. To more thoroughly assess the role of OVOL1 in syncytiotrophoblast formation, we propose compelling experiments outlined in two Aims. Aim 1 will determine what happens to the differentiation potential of human trophoblast cells when OVOL1 expression is manipulated. Aim 2 will determine how OVOL1 fits into a gene regulatory network controlling retrovirus-derived gene expression and consequently, syncytialization. We expect information accrued from experiments in Aims 1 and 2 will provide pertinent information on trophoblast syncytialization, and will shed new light on the molecular regulation of placental development. We also expect that the information garnered from these studies will provide an important foundation in our quest to understand the molecular signals governing placental development in both normal and pathological pregnancies.


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: 2017 ( Subtotal = $0 )
2017	2016	UNIVERSITY OF WESTERN ONTARIO, THE	1151 RICHMOND ST SUITE 2	LONDON	ON	N6A 5B8		CAN	Child Health and Human Development Extramural Research	000	3	8/26/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $53,460 )
2016	2016	UNIVERSITY OF WESTERN ONTARIO	1151 RICHMOND STREET N	LONDON				GBR	Child Health and Human Development Extramural Research	000	3	3/22/2016	NON-COMPETING CONTINUATION	$53,460
														Subtotal = $53,460

Issue Date FY: 2015 ( Subtotal = -$19,677 )
2015	2014	UNIVERSITY OF WESTERN ONTARIO	1151 RICHMOND STREET N	LONDON				GBR	Child Health and Human Development Extramural Research	000	2	8/21/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$49,423
2015	2014	UNIVERSITY OF KANSAS MEDICAL CENTER RESEARCH INSTITUTE	3901 RAINBOW BOULEVARD	KANSAS CITY	KS	66160	WYANDOTTE	USA	Child Health and Human Development Extramural Research	001	1	8/21/2015	NEW	-$69,100
														Subtotal = -$19,677

Issue Date FY: 2014 ( Subtotal = $75,500 )
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	1	9/22/2014	NEW	$75,500
														Subtotal = $75,500

Grand Total All Awards = $109,283

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Role of OVO-like 1 in the regulation of human trophoblast differentiation

Award Number: R03HD079850

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: 09/23/2014

PERIOD OF PERFORMANCE END DATE: 03/31/2017

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