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Progenitor Regulation in Craniofacial Development and Regeneration

Award Number: R35DE027550
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: 09/14/2017
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Progenitor Regulation in Craniofacial Development and Regeneration - Birth defects of the head and face are common in the human population. Skull injuries and joint disease, in particular affecting the temporomandibular joint of the jaw, are a major economic and societal burden. This proposal is to support the upward trajectory of a mid-career investigator, Dr. Gage Crump, who works at the interface of craniofacial development and stem cell biology. Specifically, he has developed powerful new zebrafish models of human craniofacial birth defects and disease, which are allowing him to unravel the developmental causes of common craniofacial birth defects and, in a bold new direction, to understand mechanisms of stimulating endogenous repair of the adult skull. Dr. Crump is Director of the PhD Program in Development, Stem Cells, and Regenerative Medicine at the University of Southern California and a founding member of the Eli and Edythe Broad Center for Stem Cell Research, a rapidly growing institute directed by Dr. Andrew McMahon with exceptional core resources and recently recruited junior faculty. He is currently PI on three R01's from NIDCR and has published featured articles in Developmental Cell, eLife, Development, and PLoS Genetics on diverse topics ranging from craniofacial development to jawbone repair and arthritis of the jaw. He has built up an exceptional research team, with several trainees receiving K99 and F31 fellowships from NIDCR, as well as prestigious private fellowships. His previous trainees have gone on to tenure-track faculty and industry positions, and postdocs in HHMI-funded labs. He also participates in local and national efforts to recruit under-represented minority students into stem cell science from high school to graduate levels. These efforts are reflected by a USC Mentoring Award to Dr. Crump in 2017. The research program focuses on the roles of progenitor cells in building the facial skeleton and then maintaining and repairing it in the adult. These studies exploit the unique genetic and imaging strengths of zebrafish, combined with its impressive capabilities of natural regeneration as adults. The first program uses new gene editing technology in zebrafish to analyse requirements for novel craniofacial patterning genes in progenitor regulation, as well as to directly image progenitor lineage commitment using time-lapse microscopy. As exemplified by studies of Jagged-Notch signaling from fish to man, efforts to validate zebrafish findings in mouse will be performed in latter years. The second program investigates the stem cell-based maintenance of two types of joints, the sutures of the skull and the synovial jaw joint. The third program builds on innovative models of bone, cartilage, and joint regeneration in the adult zebrafish jaw, as well as a highly collaborative network of basic researchers and clinicians at USC, to understand how different types of endogenous stem cells are activated to repair craniofacial tissues. Completion of these studies will reveal commonalities and differences between the stem cells that build and then maintain and repair the craniofacial skeleton, with foundational knowledge acquired in zebrafish informing future regenerative approaches towards improving skeletal healing in patients.


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	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	8	6/3/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $1,086,585 )
2024	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Oral Diseases and Disorders Research	001	8	6/20/2024	SUPPLEMENT FOR EXPANSION	$49,769
2024	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Oral Diseases and Disorders Research	002	8	8/22/2024	SUPPLEMENT FOR EXPANSION	$0
2024	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	8	6/12/2024	NON-COMPETING CONTINUATION	$1,036,816
														Subtotal = $1,086,585

Issue Date FY: 2023 ( Subtotal = $1,167,715 )
2023	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Oral Diseases and Disorders Research	002	7	5/17/2023	SUPPLEMENT FOR EXPANSION	$74,588
2023	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Oral Diseases and Disorders Research	001	7	5/16/2023	NON-COMPETING CONTINUATION	$1,066,225
2023	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	6	2/21/2023	SUPPLEMENT FOR EXPANSION	$26,902
														Subtotal = $1,167,715

Issue Date FY: 2022 ( Subtotal = $1,055,563 )
2022	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	6	6/8/2022	NON-COMPETING CONTINUATION	$1,055,563
														Subtotal = $1,055,563

Issue Date FY: 2021 ( Subtotal = $880,984 )
2021	2021	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Oral Diseases and Disorders Research	001	5	6/9/2021	NON-COMPETING CONTINUATION	$1,066,634
2021	2018	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	2	1/28/2021	NON-COMPETING CONTINUATION	-$185,650
														Subtotal = $880,984

Issue Date FY: 2020 ( Subtotal = $1,050,134 )
2020	2020	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	4	6/23/2020	NON-COMPETING CONTINUATION	$1,050,134
														Subtotal = $1,050,134

Issue Date FY: 2019 ( Subtotal = $1,231,659 )
2019	2019	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Oral Diseases and Disorders Research	001	3	6/10/2019	NON-COMPETING CONTINUATION	$1,046,009
2019	2018	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	2	3/29/2019	NON-COMPETING CONTINUATION	$185,650
														Subtotal = $1,231,659

Issue Date FY: 2018 ( Subtotal = $1,041,884 )
2018	2018	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER STREET THIRD FLOOR	LOS ANGELES	CA	90089	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	2	5/15/2018	NON-COMPETING CONTINUATION	$1,041,884
														Subtotal = $1,041,884

Issue Date FY: 2017 ( Subtotal = $497,041 )
2017	2017	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER STREET THIRD FLOOR	LOS ANGELES	CA	90089	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	1	9/14/2017	NEW	$497,041
														Subtotal = $497,041

Grand Total All Awards = $8,011,565

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Progenitor Regulation in Craniofacial Development and Regeneration

Award Number: R35DE027550

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: 09/14/2017

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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