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Establishing an In Vitro Embryotoxicity Risk Classification System Based on Human Cardiac Organoid Model

Award Number: R01HD101130
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 Currently, drug embryotoxicity risk for safe pregnancy is not well established, thus many pregnant women are exposed to the drugs with unknown effects on fetus development. Many drugs are still neither well understood regarding their effects on human organogenesis, nor is there a well-established human embryotoxicity drug screening platform available. Currently, human induced pluripotent stem cells (hiPSCs) have been proposed for human-relevant drug toxicity screening. However, the use of hiPSC maintenance and differentiation on 2D culture is not an ideal embryotoxicity assay due to their inability to predict the drug toxicity on 3D tissue morphogenesis, which potentially leads to the structural malformations manifested in late prenatal fetus development. With the emergent concept of stem cell organoids, these 3D cultures of developing tissues imply the similarity to the manner in which different organs establish their characteristic organization during development. Therefore, the overall goal of this proposal is to establish an in vitro hiPSC-based cardiac organoid model for embryotoxicity testing based on the drug effects on hiPSC growth, cardiac differentiation, and early heart formation, so we can establish a risk classification system for more precise assessment of human-specific drug effects on early embryonic development. To achieve this goal, we will pursue three specific aims. In Aim 1, we will optimize the cardiac organoid model by investigating the effects of biophysical confinement on the formation and function of cardiac organoids. In Aim 2, we will validate the cardiac organoid-based embryotoxicity assay by comparing to well-established standard zebrafish whole embryo culture assay. By testing a “training set” of chemicals with known embryotoxicity level, we will better calibrate the drug response from human cardiac organoids based on a variety of endpoint evaluation parameters. In Aim 3, we will establish a new biostatistical predictive model based on linear discriminant analysis for embryotoxicity risk classification. We envisage that this in vitro cardiac organoid model can improve traditional pharmaceutical screening for the drugs that will be administered during 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: 2024 ( Subtotal = $0 )
2024	2023	SYRACUSE UNIVERSITY	900 S CROUSE AVE	SYRACUSE	NY	13244	ONONDAGA	USA	Child Health and Human Development Extramural Research	000	4	3/18/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $458,224 )
2023	2023	SYRACUSE UNIVERSITY	900 S CROUSE AVE	SYRACUSE	NY	13244	ONONDAGA	USA	Child Health and Human Development Extramural Research	000	4	2/28/2023	NON-COMPETING CONTINUATION	$458,224
														Subtotal = $458,224

Issue Date FY: 2022 ( Subtotal = $446,702 )
2022	2022	SYRACUSE UNIVERSITY	900 S CROUSE AVE STE 620	SYRACUSE	NY	13244	ONONDAGA	USA	Child Health and Human Development Extramural Research	000	3	2/2/2022	NON-COMPETING CONTINUATION	$402,030
2022	2022	SYRACUSE UNIVERSITY	900 S CROUSE AVE STE 620	SYRACUSE	NY	13244	ONONDAGA	USA	Child Health and Human Development Extramural Research	001	3	4/27/2022	NON-COMPETING CONTINUATION	$44,672
														Subtotal = $446,702

Issue Date FY: 2021 ( Subtotal = $446,702 )
2021	2021	SYRACUSE UNIVERSITY	900 S CROUSE AVE STE 620	SYRACUSE	NY	13244	ONONDAGA	USA	Child Health and Human Development Extramural Research	001	2	3/31/2021	NON-COMPETING CONTINUATION	$0
2021	2021	SYRACUSE UNIVERSITY	900 S CROUSE AVE STE 620	SYRACUSE	NY	13244	ONONDAGA	USA	Child Health and Human Development Extramural Research	000	2	2/25/2021	NON-COMPETING CONTINUATION	$446,702
														Subtotal = $446,702

Issue Date FY: 2020 ( Subtotal = $468,319 )
2020	2020	SYRACUSE UNIVERSITY	900 S CROUSE AVE STE 620	SYRACUSE	NY	13244	ONONDAGA	USA	Child Health and Human Development Extramural Research	000	1	3/25/2020	NEW	$468,319
														Subtotal = $468,319

Grand Total All Awards = $1,819,947

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Establishing an In Vitro Embryotoxicity Risk Classification System Based on Human Cardiac Organoid Model

Award Number: R01HD101130

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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