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Spatiotemporal mechanical inhomogeneities in the embryonic oral epithelium and mesenchyme lead to tooth invagination

Award Number: F32DE030004
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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Spatiotemporal mechanical inhomogeneities in the embryonic oral epithelium and mesenchyme lead to tooth invagination - Project Summary-Abstract Adult tooth loss is an undesirable consequence of dental disease or injury that affects a majority of Americans. Thus, it has become the aim and challenge of bioengineers and regenerative medicine scientists to understand the fundamental principles by which native tissue structures grow and form, and apply this knowledge to recreate oral structures.1 A better understanding of how embryonic teeth develop, especially at early stages of tooth formation (placode organization and initiation of epithelial invagination), is paramount. The primary goal of this proposal is to understand the mechanisms behind the development of embryonic mouse incisor tooth germs. While the process by which biochemical signaling initiates placode formation and position is well described,2 much less is known about how spatiotemporal patterns of physical cues, such as cell-generated forces and tissue elastic properties, influence tooth germ invagination. Hypothesis: Spatially-defined differences in cell tension and tissue stiffness (on the order of tens of microns) drive the epithelial invagination process. The main innovation of this project will be the cutting edge mechanical measurement techniques that I will develop and apply to functionally understand mechanical contributions to tooth germ formation. I will first determine the functional role of epithelial force generation in driving epithelial invagination. Second, I will determine the mesenchyme mechanical contribution on epithelial invagination. And third, I will create an in vitro model of the mouse mandible at the incisor region to examine the interplay between mechanical and soluble chemical cues on epithelial invagination. Accomplishing these aims will allow me to ascertain the mechanics of the developing tooth germ, how mechanical properties of the germ affect and are affected by signaling pathways, and how this interplay contributes to the invagination process. Altogether, these experiments will lay the groundwork to develop regenerative medicine and tissue engineering strategies to grow a functional tooth. This fellowship training plan and the environment in which the research training will take place will foster my growth as a young scientist, and career path as an independent investigator. I intend to develop my skills in fundamental and molecular biology. Coming from the chemical and physical sciences, this fellowship experience will allow me to immerse myself in a new environment with people whose skillset is very different than my own. I will forge a new, multidisciplinary research direction and expand my unique research toolbox. I believe this opportunity will best allow me to study the interface between biology and solid mechanics. This combination of institute, sponsors, and project will enhance my training as an independent researcher and field leader in cross- sector investigations.


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	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	3	9/23/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $70,300 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	3	12/2/2022	NON-COMPETING CONTINUATION	$68,382
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Oral Diseases and Disorders Research	001	3	2/28/2023	NON-COMPETING CONTINUATION	$1,918
														Subtotal = $70,300

Issue Date FY: 2022 ( Subtotal = $67,974 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Oral Diseases and Disorders Research	002	2	5/24/2022	NON-COMPETING CONTINUATION	$389
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Oral Diseases and Disorders Research	003	2	8/18/2022	NON-COMPETING CONTINUATION	$0
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	2	11/30/2021	NON-COMPETING CONTINUATION	$66,794
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Oral Diseases and Disorders Research	004	2	8/26/2022	NON-COMPETING CONTINUATION	$0
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Oral Diseases and Disorders Research	001	2	4/28/2022	NON-COMPETING CONTINUATION	$791
														Subtotal = $67,974

Issue Date FY: 2020 ( Subtotal = $65,354 )
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	1	6/22/2020	NEW	$65,354
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Oral Diseases and Disorders Research	001	1	6/22/2020	NEW	$0
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Oral Diseases and Disorders Research	002	1	9/1/2020	NEW	$0
														Subtotal = $65,354

Grand Total All Awards = $203,628

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Spatiotemporal mechanical inhomogeneities in the embryonic oral epithelium and mesenchyme lead to tooth invagination

Award Number: F32DE030004

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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