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Mechanisms of Oral Epithelial Differentiation

Award Number: K08DE026537
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 12/16/2020
PERIOD OF PERFORMANCE END DATE: 12/17/2020

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Mechanisms of Oral Epithelial Differentiation - ABSTRACT This application is for a Mentored Clinical Scientist Research Career Development Award (K08) for Dr. Kevin Byrd. He is currently conducting research into the role of mitotic spindle orientation in oral epithelial development and has observed that during oral mucosal epithelial development, perpendicular divisions become more numerous and are essential for differentiation. This K08 will allow Dr. Byrd to 1) become an expert in oral epithelial differentiation through molecular regulation of mitotic spindle positioning, 2) to conduct basic science research in vivo in a tissue rarely studied, 3) to gain the skills to utilize ex vivo organotypic models to describe this phenomenon in human oral epithelial differentiation, 4) to gain the skills necessary to collaborate and to perform “-omics” approaches in oral epithelial stem cell identification, and 5) to develop an independent science research career that will allow him to ask questions in collaboration with clinical and basic scientists. A multidisciplinary team of experts have agreed to provide invaluable support to him upon funding of this application: 1) Drs. Eric Everett (basic science; dental research), Susan Henning (basic science; gastrointestinal research), Steven Offenbacher (translational and clinical science, dental research, and Dr. Ophir Klein (clinician-scientist: GI and dental stem cells), 2) research training by epithelia and oral biology experts: primary mentor, Dr. Scott Williams and co-mentor, Dr. Jennifer Webster-Cyriaque, and 3) RNA-seq and bioinformatics training: (Drs. Piotr Mieczkowski, Scott Magness, and Di Wu). These mentors and the training they make available will provide him with the skills to become a successful, independent investigator. The paucity of oral epithelial mouse models has resulted in minimal characterization of oral epithelial differentiation networks, and a poor understanding of oral epithelial stem cells and their niches. Based on his rapid generation (8-12 weeks total) of an oral epithelia mouse model, Dr. Byrd has already shown that the mitotic spindle orientation gene LGN (Gpsm2) is essential in promoting differentiation and tissue patterning in the oral cavity. The pace and specificity in which he can generate new oral epithelial mouse models where few exist—weeks as opposed to months or years—is unprecedented compared to traditional methods. Dr. Byrd's research will focus on oral epithelial differentiation, which is critical in understanding how the oral cavity heals in response to injury. This project will create three novel, oral epithelial mouse models and surrogate ex vivo human models to assess the role of oriented cell divisions in oral epithelial differentiation (Aim 1 and 2), and will utilize a unbiased, genetic label retaining cell model to identify and profile quiescent cells from oral basal epithelial cells (Aim 3). Dr. Byrd's research will inform the basis of a future project on reserve stem cell function in oral epithelial wound healing, to be proposed in the last year of the funding period (K99/R00).


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 = -$82,397 )
2023	2020	ADA SCIENCE & RESEARCH INSTITUTE LLC	211 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Oral Diseases and Disorders Research	000	6	10/11/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$82,397
														Subtotal = -$82,397

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2020	ADA SCIENCE AND RESEARCH INSTITUTE LLC	211 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Oral Diseases and Disorders Research	001	6	6/2/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$81,909
2021	2020	ADA SCIENCE AND RESEARCH INSTITUTE LLC	211 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Oral Diseases and Disorders Research	004	6	8/7/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$488
2021	2020	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Oral Diseases and Disorders Research	000	5	6/1/2021	NON-COMPETING CONTINUATION	-$81,909
2021	2020	ADA SCIENCE AND RESEARCH INSTITUTE LLC	211 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Oral Diseases and Disorders Research	002	6	6/18/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2021	2019	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Oral Diseases and Disorders Research	003	4	8/7/2021	NON-COMPETING CONTINUATION	-$488
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $81,909 )
2020	2020	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Oral Diseases and Disorders Research	000	5	8/11/2020	NON-COMPETING CONTINUATION	$81,909
														Subtotal = $81,909

Issue Date FY: 2019 ( Subtotal = $79,801 )
2019	2019	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Oral Diseases and Disorders Research	000	4	7/31/2019	NON-COMPETING CONTINUATION	$79,801
														Subtotal = $79,801

Issue Date FY: 2018 ( Subtotal = $89,580 )
2018	2018	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Oral Diseases and Disorders Research	000	3	7/27/2018	NON-COMPETING CONTINUATION	$89,580
														Subtotal = $89,580

Issue Date FY: 2017 ( Subtotal = $89,580 )
2017	2017	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Oral Diseases and Disorders Research	000	2	8/17/2017	NON-COMPETING CONTINUATION	$89,580
														Subtotal = $89,580

Issue Date FY: 2016 ( Subtotal = $89,580 )
2016	2016	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Oral Diseases and Disorders Research	000	1	9/12/2016	NEW	$89,580
														Subtotal = $89,580

Grand Total All Awards = $348,053

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Mechanisms of Oral Epithelial Differentiation

Award Number: K08DE026537

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 12/16/2020

PERIOD OF PERFORMANCE END DATE: 12/17/2020

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