Tuesday, January 28, 2025 1/28/2025

Genetic Regulatory Network in Craniofacial Development

Award Number: R01DE015654
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Title Genetic Regulatory Network in Craniofacial Development Abstract This proposal continues our efforts to decipher the skeletogenic signaling network underlying craniofacial development and disease. The craniofacial skeleton consists of viscerocranium and neurocranium, which is subdivided into the calvarium and chondrocranium. During development of the calvarium, cranial sutures serve as the growth center for skeletogenesis. Defects in suture morphogenesis resulting in premature closure cause craniosynostosis, a devastating childhood disease affecting 1 in ~2,500 individuals. Although human genetic analyses have identified genes associated with the pathogenesis, little is known about the regulation of suture closure essential for development of a healthy skull. In the previously proposed investigation, we have elucidated the mechanisms by which Axin2 regulates suture morphogenesis through modulations of Wnt and downstream signaling pathways. The crosstalk of BMP and FGF signaling plays a pivotal role in Wnt-mediated craniofacial bone development. Furthermore, skeletal stem cells residing in the suture mesenchyme have been successfully identified and isolated in our laboratory. This suture stem cell (SuSC) population is responsible for calvarial development in infants as well as homeostatic maintenance in adults. Upon injury, the dormant SuSCs respond quickly and contribute directly to bone repair in a cell autonomous fashion. In vivo clonal analysis demonstrates calvarial bone regeneration at a single cell level. Implantation of SuSCs to an injured site shows not only long-term survival but also facilitation of bone healing via direct engraftments in which the implanted stem cells give rise to osteogenic cell types in replacement of the damaged tissue. The newly discovered SuSCs thus provides an outstanding opportunity to gain novel insights into etiology of craniosynostosis. In this proposal, we continue our in-depth evaluations of SuSCs by examining their regulation essential for healthy development and homeostasis of the calvarium. We will concentrate on elucidation of molecular and cellular mechanisms underlying craniosynostosis caused by dysregulation of SuSCs.


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: 2023 ( Subtotal = $668,811 )
2023	2023	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	16	1/12/2023	NON-COMPETING CONTINUATION	$601,931
2023	2023	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	001	16	2/23/2023	NON-COMPETING CONTINUATION	$66,880
														Subtotal = $668,811

Issue Date FY: 2022 ( Subtotal = $662,124 )
2022	2022	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	005	15	4/20/2022	NON-COMPETING CONTINUATION	$60,193
2022	2022	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	001	15	1/6/2022	NON-COMPETING CONTINUATION	$601,931
2022	2021	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	14	1/5/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2022	2021	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	003	13	2/14/2022	NON-COMPETING CONTINUATION	-$125,527
2022	2021	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	004	14	2/14/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$202,065
2022	2020	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	002	12	2/14/2022	NON-COMPETING CONTINUATION	-$76,538
														Subtotal = $662,124

Issue Date FY: 2021 ( Subtotal = $632,131 )
2021	2021	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	002	13	8/30/2021	NON-COMPETING CONTINUATION	-$392,045
2021	2021	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	000	13	2/1/2021	NON-COMPETING CONTINUATION	$465,816
2021	2021	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	003	14	8/31/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$506,604
2021	2021	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	001	13	2/23/2021	NON-COMPETING CONTINUATION	$51,756
														Subtotal = $632,131

Issue Date FY: 2020 ( Subtotal = $517,572 )
2020	2020	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	000	12	1/28/2020	NON-COMPETING CONTINUATION	$465,816
2020	2020	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	001	12	2/20/2020	NON-COMPETING CONTINUATION	$51,756
														Subtotal = $517,572

Issue Date FY: 2019 ( Subtotal = $517,572 )
2019	2019	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	002	11	7/18/2019	COMPETING CONTINUATION	$389
2019	2019	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	000	11	2/12/2019	COMPETING CONTINUATION	$517,572
2019	2016	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	001	10	7/18/2019	EXTENSION WITH OR WITHOUT FUNDS	-$389
														Subtotal = $517,572

Issue Date FY: 2018 ( Subtotal = $0 )
2018	2016	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	000	10	5/3/2018	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $386,250 )
2016	2016	UNIVERSITY OF ROCHESTER	1325 MOUNT HOPE AVE, SUITE 260	ROCHESTER	NY	14642	MONROE	USA	Oral Diseases and Disorders Research	000	10	4/15/2016	EXTENSION WITH OR WITHOUT FUNDS	$386,250
														Subtotal = $386,250

Issue Date FY: 2015 ( Subtotal = $386,250 )
2015	2015	UNIVERSITY OF ROCHESTER	1325 MOUNT HOPE AVE, SUITE 260	ROCHESTER	NY	14642	MONROE	USA	Oral Diseases and Disorders Research	000	9	4/21/2015	NON-COMPETING CONTINUATION	$386,250
														Subtotal = $386,250

Issue Date FY: 2014 ( Subtotal = $386,250 )
2014	2014	UNIVERSITY OF ROCHESTER	1325 MOUNT HOPE AVE, SUITE 260	ROCHESTER	NY	14642	MONROE	USA	Oral Diseases and Disorders Research	000	8	4/15/2014	NON-COMPETING CONTINUATION	$386,250
														Subtotal = $386,250

Issue Date FY: 2013 ( Subtotal = $370,800 )
2013	2013	UNIVERSITY OF ROCHESTER	1325 MOUNT HOPE AVE, SUITE 260	ROCHESTER	NY	14642	MONROE	USA	Oral Diseases and Disorders Research	000	7	5/28/2013	NON-COMPETING CONTINUATION	$370,800
														Subtotal = $370,800

Issue Date FY: 2012 ( Subtotal = $386,250 )
2012	2012	UNIVERSITY OF ROCHESTER	1325 MOUNT HOPE AVE, SUITE 260	ROCHESTER	NY	14642	MONROE	USA	Oral Diseases and Disorders Research	000	6	6/5/2012	COMPETING CONTINUATION	$386,250
														Subtotal = $386,250

Issue Date FY: 2010 ( Subtotal = $340,295 )
2010	2010	UNIVERSITY OF ROCHESTER	1325 MOUNT HOPE AVE, SUITE 260	ROCHESTER	NY	14642	MONROE	USA	Oral Diseases and Disorders Research	000	5	5/27/2010	NON-COMPETING CONTINUATION	$340,295
														Subtotal = $340,295

Issue Date FY: 2009 ( Subtotal = $343,751 )
2009	2009	UNIVERSITY OF ROCHESTER	1325 MOUNT HOPE AVE, SUITE 260	ROCHESTER	NY	14642	MONROE	USA	Oral Diseases and Disorders Research	000	4	5/5/2009	NON-COMPETING CONTINUATION	$343,751
														Subtotal = $343,751

Issue Date FY: 2008 ( Subtotal = $343,775 )
2008	2008	UNIVERSITY OF ROCHESTER	1325 MOUNT HOPE AVE, SUITE 260	ROCHESTER	NY	14620	MONROE	USA	Oral Diseases and Disorders Research	000	3	5/20/2008	NON-COMPETING CONTINUATION	$343,775
														Subtotal = $343,775

Issue Date FY: 2007 ( Subtotal = $347,622 )
2007	2007	UNIVERSITY OF ROCHESTER	1325 MOUNT HOPE AVE, SUITE 260	ROCHESTER	NY	14620	MONROE	USA	Oral Diseases and Disorders Research	000	2	6/14/2007	NON-COMPETING CONTINUATION	$347,622
														Subtotal = $347,622

Issue Date FY: 2006 ( Subtotal = $358,027 )
2006	2006	UNIVERSITY OF ROCHESTER	1325 MOUNT HOPE AVE, SUITE 260	ROCHESTER	NY	14620	MONROE	USA	Oral Diseases and Disorders Research	000	1	6/7/2006	NEW	$358,027
														Subtotal = $358,027

Grand Total All Awards = $6,647,480

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Genetic Regulatory Network in Craniofacial Development

Award Number: R01DE015654

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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