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Growth factors-induced dentinogenesis

Award Number: R01DE025885
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2017
PERIOD OF PERFORMANCE END DATE: 08/31/2023

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Growth factors-induced dentinogenesis - Project summary: There is an increasing need to develop strategies for pulp regeneration therapy to overcome tooth injury due to caries, restorative procedures, or trauma. Currently, there is a significant gap in our understanding of the molecular and cellular mechanisms regulating reparative dentinogenesis. Our long-term goal is to gain fundamental knowledge on the human dental pulp cellular niche and to apply that knowledge to lessen the burdens of tooth injury due to caries, restorative procedures, or trauma. The objective for this application is to elucidate how the interactions between ephrinB1 and IGF-1 in the dental pulp niche induce dentinogenesis in vivo. The overarching hypothesis is that IGF-1 regulates cells of the tooth pulp niche, and induces dentinogenesis via ephrinB1. Guided by strong preliminary data, this hypothesis will be tested by pursuing the following two specific aims: Aim 1: Determine the mechanism by which ephrinB1 controls the number of odontoblast progenitors, their proliferation, and differentiation in the tooth pulp. And Aim 2: Determine the cellular and molecular mechanisms by which IGF-1 regulates ephrinB1 expression in vivo using mouse models and ex vivo using human DPSCs and human oral mucosa stem cells. An already-generated odontoblast-specific ephrinB1 knockout mouse lines (using cre driven by the DMP1 or osteocalcin promoters), and mouse lines of IGF-1 receptor (DMP1-IGF-1RKO) and the hepatic IGF-1 transgenic (HIT) line will be used to achieve the two aims. Importantly, initial characterization of our models indicates that both IGF-1 and ephrinB1 involved in dentinogenesis in vivo. The proposed research is conceptually innovative because we show, for the first time, the interactions between ephrinB1 and IGF-1 during dentinogenesis in vivo. Further, we offer a direct approach to determine these interactions using unique mouse models, as well as primary human dental pulp cell cultures. The proposed research is significant because it is expected to advance the field of regenerative endodontic procedures and will impact the overall effort to retain the natural tertiary dentin formation process following injury.


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	2020	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	110 BERGEN ST	NEWARK	NJ	07103	ESSEX	USA	Oral Diseases and Disorders Research	000	6	5/28/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	110 BERGEN ST	NEWARK	NJ	07103	ESSEX	USA	Oral Diseases and Disorders Research	000	6	7/13/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $65,885 )
2021	2021	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	110 BERGEN ST	NEWARK	NJ	07103	ESSEX	USA	Oral Diseases and Disorders Research	001	6	11/18/2020	SUPPLEMENT FOR EXPANSION	-$24,322
2021	2021	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	110 BERGEN ST	NEWARK	NJ	07103	ESSEX	USA	Oral Diseases and Disorders Research	000	6	11/16/2020	SUPPLEMENT FOR EXPANSION	$90,207
														Subtotal = $65,885

Issue Date FY: 2020 ( Subtotal = $397,404 )
2020	2020	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	110 BERGEN ST	NEWARK	NJ	07103	ESSEX	USA	Oral Diseases and Disorders Research	000	6	8/13/2020	NON-COMPETING CONTINUATION	$397,404
														Subtotal = $397,404

Issue Date FY: 2019 ( Subtotal = $397,404 )
2019	2019	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	110 BERGEN ST	NEWARK	NJ	07103	ESSEX	USA	Oral Diseases and Disorders Research	000	5	7/16/2019	NON-COMPETING CONTINUATION	$397,404
														Subtotal = $397,404

Issue Date FY: 2018 ( Subtotal = $397,404 )
2018	2018	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	110 BERGEN ST	NEWARK	NJ	07103	ESSEX	USA	Oral Diseases and Disorders Research	000	4	8/10/2018	NON-COMPETING CONTINUATION	$397,404
														Subtotal = $397,404

Issue Date FY: 2017 ( Subtotal = $397,404 )
2017	2017	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	110 BERGEN ST	NEWARK	NJ	07103	ESSEX	USA	Oral Diseases and Disorders Research	002	3	8/22/2017	NON-COMPETING CONTINUATION	$397,404
2017	2016	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Oral Diseases and Disorders Research	000	1	8/7/2017	NEW	-$265,000
2017	2016	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	110 BERGEN ST	NEWARK	NJ	07103	ESSEX	USA	Oral Diseases and Disorders Research	001	2	8/9/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$265,000
														Subtotal = $397,404

Issue Date FY: 2016 ( Subtotal = $396,250 )
2016	2016	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Oral Diseases and Disorders Research	000	1	7/11/2016	NEW	$396,250
														Subtotal = $396,250

Grand Total All Awards = $2,051,751

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Growth factors-induced dentinogenesis

Award Number: R01DE025885

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/01/2017

PERIOD OF PERFORMANCE END DATE: 08/31/2023

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