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Systematic Reconstruction of Epithelial-Mesenchymal Communication in Organ Development

Award Number: DP2HD108777
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: 08/15/2021
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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Systematic Reconstruction of Epithelial-Mesenchymal Communication in Organ Development - PROJECT SUMMARY Mesenchymal cells are major components of tissue stroma and best known for their role in supporting the physical structure of organs. They juxtapose to and communicate with epithelial cells, to control organ development in embryos, and to regulate tissue inflammation, injury repair and cancer progression in adults. Traditionally, mesenchymal cells in different organs were thought to perform similar functions. However, recent studies have revealed unexpected diversity of gene expression signatures among mesenchymal cells from different organs. Such diversity is likely to play a crucial role in regulating mesenchymal-epithelial interactions and thus organ development and physiology. The overarching goal of this proposal is to understand how epithelial-mesenchymal interactions control organogenesis across different organs. To achieve this goal, we will first address the question of how mesenchymal diversity arises as the consequence of distinct signaling histories. We will develop a novel high-throughput system to simultaneously test tens of thousands of signal combinations. We will then investigate how epithelial-mesenchymal interactions control tissue morphogenesis, by reconstituting and genetically perturbing such interactions ex vivo. We are especially interested in comparing the specificity and plasticity of epithelial-mesenchymal interactions across different organs, and identifying the role of extracellular matrices that are shared by epithelial and mesenchymal cells in controlling morphogenesis. We will closely integrate experimental measurements with computational models to produce a quantitative framework for understanding organ morphogenesis. By integrating tools and materials from diverse fields, we will gain a fundamental understanding about the developmental origin and functional implications of the long-overlooked mesenchymal cells. These insights and tools will enable the engineering of organoids to better model development and diseases, and will advance the field of tissue engineering.


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 = $0 )
2025	2024	WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH	455 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Child Health and Human Development Extramural Research	001	2	10/10/2024	EXTENSION WITH OR WITHOUT FUNDS	$591,113
2025	2021	WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH	455 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Child Health and Human Development Extramural Research	000	1	10/10/2024	NEW	-$591,113
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $1,163,081 )
2024	2024	WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH	455 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Child Health and Human Development Extramural Research	000	2	8/15/2024	EXTENSION WITH OR WITHOUT FUNDS	$1,163,081
														Subtotal = $1,163,081

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH	455 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Child Health and Human Development Extramural Research	000	1	9/26/2022	NEW	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $1,755,000 )
2021	2021	WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH	455 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Child Health and Human Development Extramural Research	000	1	9/21/2021	NEW	$1,755,000
														Subtotal = $1,755,000

Grand Total All Awards = $2,918,081

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Systematic Reconstruction of Epithelial-Mesenchymal Communication in Organ Development

Award Number: DP2HD108777

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: 08/15/2021

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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