Monday, June 30, 2025 6/30/2025

Regulation of epithelial barrier

Award Number: R01DE031046
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: 11/10/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Regulation of epithelial barrier - Project summary Periodontitis and peri-implantitis are oral diseases characterized by loss of oral homeostasis and induction of inflammation. Although downstream inflammatory events that occur in connective tissue have been well recognized, the regulatory pathways involved in epithelial barrier function in these diseases has not been explored in detail. In this study, we aim to identify key spatiotemporal mechanisms that control epithelial barrier function. Although it is recognized that epithelial barrier function is critical it's regulation is not well understood. To address this, in vivo and in vitro experimental models, such as Epi-oral device, have been developed. Based on Prel Data we will investigate the role of FOXO1, E-cadherin and β−catenin in the maintenance and loss of barrier function through bacteria induced signaling. Preliminary Data demonstrate that pressure enhances epithelial barrier and directs E-cadherin/β−catenin to cell membranes and FOXO1 to the cytoplasm. E.coli LPS, a TLR4 agonist, reverses this behavior and directs FOXO1 and β−catenin to the nucleus and from cell membranes E-cadherin. These data serve as the basis to mechanistically investigate the role of mechanical pressure on promoting epithelial integrity and its disruption by E.coli LPS and F. nucleatum, an important oral bacterium, by use of the Epi-oral platform (Aim1). Next, we will investigate how epithelial attachment to titanium may affect barrier function in studies that will give insight into processes that are important in peri-implantitis. Specifically, we will examine how the interaction of keratinocytes-titanium, as underlying matrix, regulates keratinocytes in the presence of pressure or E.coli LPS and F. nucleatum (Aim2). Finally, we will investigate how FOXO1, β−catenin and E-cadherin are modulated in healthy tissue compared to inflamed tissue in vivo. Animal experiments will involve mechanistic studies to examine the role of upstream events in barrier function by lineage specific deletion of FOXO1 and TLR4 in keratinocytes in vivo, to examine dysregulation of β−catenin, E-cadherin and the formation of tight junctions. Similar studies will be examined in human tissue from non- inflamed gingiva, and gingiva from patients with periodontitis and peri-implantitis sites to determine if similar dysregulation occurs in these disease processes (Aim3). Given the recognized fundamental importance of the complexity in oral diseases, these studies may pave the way to identify novel targets for treatments against periodontitis and peri-implantitis.


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 = $432,080 )
2025	2025	GEORGETOWN UNIVERSITY	MAIN CAMPUS	WASHINGTON	DC	20057	DISTRICT OF COLUMBIA	USA	Oral Diseases and Disorders Research	000	6	5/21/2025	NON-COMPETING CONTINUATION	$432,080
														Subtotal = $432,080

Issue Date FY: 2024 ( Subtotal = $432,314 )
2024	2024	GEORGETOWN UNIVERSITY	MAIN CAMPUS	WASHINGTON	DC	20057	DISTRICT OF COLUMBIA	USA	Oral Diseases and Disorders Research	000	5	5/30/2024	NON-COMPETING CONTINUATION	$432,314
														Subtotal = $432,314

Issue Date FY: 2023 ( Subtotal = $470,261 )
2023	2023	GEORGETOWN UNIVERSITY	MAIN CAMPUS	WASHINGTON	DC	20057	DISTRICT OF COLUMBIA	USA	Oral Diseases and Disorders Research	005	4	5/26/2023	NON-COMPETING CONTINUATION	$470,261
2023	2022	GEORGETOWN UNIVERSITY	MAIN CAMPUS	WASHINGTON	DC	20057	DISTRICT OF COLUMBIA	USA	Oral Diseases and Disorders Research	001	3	1/12/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$465,557
2023	2022	ADA SCIENCE & RESEARCH INSTITUTE LLC	211 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Oral Diseases and Disorders Research	003	2	5/18/2023	NON-COMPETING CONTINUATION	-$1
2023	2022	ADA SCIENCE AND RESEARCH INSTITUTE LLC	211 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Oral Diseases and Disorders Research	000	2	1/11/2023	NON-COMPETING CONTINUATION	-$465,557
2023	2022	GEORGETOWN UNIVERSITY	MAIN CAMPUS	WASHINGTON	DC	20057	DISTRICT OF COLUMBIA	USA	Oral Diseases and Disorders Research	004	3	5/18/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$278,853
2023	2021	ADA SCIENCE & RESEARCH INSTITUTE LLC	211 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Oral Diseases and Disorders Research	002	1	5/18/2023	NEW	-$278,852
														Subtotal = $470,261

Issue Date FY: 2022 ( Subtotal = $465,558 )
2022	2022	ADA SCIENCE AND RESEARCH INSTITUTE LLC	211 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Oral Diseases and Disorders Research	002	2	5/26/2022	NON-COMPETING CONTINUATION	$465,558
2022	2021	ADA SCIENCE AND RESEARCH INSTITUTE LLC	211 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Oral Diseases and Disorders Research	000	1	10/8/2021	NEW	$0
2022	2021	ADA SCIENCE AND RESEARCH INSTITUTE LLC	211 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Oral Diseases and Disorders Research	001	1	1/7/2022	NEW	$0
														Subtotal = $465,558

Issue Date FY: 2021 ( Subtotal = $456,254 )
2021	2021	ADA SCIENCE AND RESEARCH INSTITUTE LLC	211 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Oral Diseases and Disorders Research	000	1	8/10/2021	NEW	$456,254
														Subtotal = $456,254

Grand Total All Awards = $2,256,467

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Regulation of epithelial barrier

Award Number: R01DE031046

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: 11/10/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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