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Oral Epithelial Cells, Candida and PMN Activation

Award Number: R01DE013986
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: 05/05/2026
PERIOD OF PERFORMANCE END DATE: 02/28/2031

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Oral Epithelial Cells, Candida and PMN Activation - Abstract Oropharyngeal Candidiasis (OPC) is a common fungal infection afflicting populations with immature or weakened immune systems. Like other oral diseases in which commensal microbes become pathogenic, OPC is associated with a dysbiotic state, an alteration in the composition and abundance of the oral health- associated bacteria, contributing to a permissive environment for Candida spp. infection. An aging population, the rise in the use of immune-compromising treatments and the increasing prevalence of drug- resistant Candida strains make it imperative to find alternative treatments for OPC. While microbiome manipulation therapies have been effective in intestinal dysbiotic diseases, none have yet been established for oral microbiome-related diseases. Microbiome directed therapies include reconstitution with probiotic bacterial consortia, that can promote oral mucosal homeostasis. It remains extremely important not only to discover new probiotic organisms but also to unravel their mechanism of action and understand their strain- specific effect. Work in our previous funding cycle showed that C. albicans causes a severe dysbiotic shift in the oral mucosal microbiota with significant reduction in bacterial alpha diversity. We also demonstrated pathogenic synergy of indigenous dysbiotic bacteria with C. albicans and identified cellular and molecular mechanisms of this synergy. Importantly, using two different types of dietary interventions in the murine OPC model we found that the oral bacterial dysbiotic shift is reversible and that diet-induced increased abundance of the commensal species Lactobacillus johnsonii is associated with less severe infection. In the next funding cycle, we propose to demonstrate that L. johnsonii induces changes in the oral bacterial microbiome consistent with mucosal homeostasis and examine mechanisms of this activity (aim 1). We also propose to demonstrate a role for this organism and its associated symbiotic bacteria in limiting the risk of C. albicans infection in immunosuppressed hosts (aim 2). In aim 3 we will dive deeper in the mechanism of protection of the oral mucosal barrier by evaluating the ability of L. johnsonii to inhibit oral epithelial adhesion, invasion and damage by C. albicans; and to inhibit Candida-induced mucosal inflammation and barrier breach. Our innovative studies will explore probiotic bacterial mechanisms that leverage the interactions between resident host bacterial microbiota, oral epithelial cells and opportunistic pathogenic fungi, providing a foundational step towards personalized, microbiome-centered treatments beyond traditional antifungal medications in oropharyngeal candidiasis. This research proposal is significant because it advances the search for alternative microbiome-targeted therapies in oral fungal infections.


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: 2026 ( Subtotal = $695,970 )
2026	2026	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Oral Diseases and Disorders Research	001	21	5/5/2026	COMPETING CONTINUATION	$695,970
2026	2024	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Oral Diseases and Disorders Research	000	20	5/1/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $695,970

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Oral Diseases and Disorders Research	000	20	5/7/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $507,193 )
2024	2024	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Oral Diseases and Disorders Research	000	20	7/23/2024	NON-COMPETING CONTINUATION	$507,193
														Subtotal = $507,193

Issue Date FY: 2023 ( Subtotal = $585,220 )
2023	2023	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Oral Diseases and Disorders Research	000	19	7/17/2023	NON-COMPETING CONTINUATION	$585,220
														Subtotal = $585,220

Issue Date FY: 2022 ( Subtotal = $564,656 )
2022	2022	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Oral Diseases and Disorders Research	000	18	7/18/2022	NON-COMPETING CONTINUATION	$564,656
														Subtotal = $564,656

Issue Date FY: 2021 ( Subtotal = $576,344 )
2021	2021	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Oral Diseases and Disorders Research	002	17	7/14/2021	NON-COMPETING CONTINUATION	$576,344
2021	2020	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Oral Diseases and Disorders Research	001	16	2/2/2021	COMPETING CONTINUATION	$53
2021	2018	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Oral Diseases and Disorders Research	000	15	2/2/2021	NON-COMPETING CONTINUATION	-$53
														Subtotal = $576,344

Issue Date FY: 2020 ( Subtotal = $576,344 )
2020	2020	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Oral Diseases and Disorders Research	000	16	7/31/2020	COMPETING CONTINUATION	$576,344
														Subtotal = $576,344

Issue Date FY: 2018 ( Subtotal = $398,750 )
2018	2018	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Oral Diseases and Disorders Research	000	15	4/24/2018	NON-COMPETING CONTINUATION	$398,750
														Subtotal = $398,750

Issue Date FY: 2017 ( Subtotal = $398,750 )
2017	2017	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Oral Diseases and Disorders Research	000	14	5/19/2017	NON-COMPETING CONTINUATION	$398,750
														Subtotal = $398,750

Issue Date FY: 2016 ( Subtotal = $398,750 )
2016	2016	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON CENTER	FARMINGTON	CT	06030	CAPITOL	USA	Oral Diseases and Disorders Research	000	13	4/6/2016	NON-COMPETING CONTINUATION	$398,750
														Subtotal = $398,750

Issue Date FY: 2015 ( Subtotal = $398,583 )
2015	2015	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON CENTER	FARMINGTON	CT	06030	CAPITOL	USA	Oral Diseases and Disorders Research	000	12	4/2/2015	NON-COMPETING CONTINUATION	$398,583
														Subtotal = $398,583

Issue Date FY: 2014 ( Subtotal = $412,250 )
2014	2014	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON CENTER	FARMINGTON	CT	06030	CAPITOL	USA	Oral Diseases and Disorders Research	001	11	7/3/2014	COMPETING CONTINUATION	-$32,155
2014	2014	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON CENTER	FARMINGTON	CT	06030	CAPITOL	USA	Oral Diseases and Disorders Research	000	11	6/27/2014	COMPETING CONTINUATION	$444,405
														Subtotal = $412,250

Issue Date FY: 2013 ( Subtotal = $0 )
2013	2011	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON CENTER	FARMINGTON	CT	06032	CAPITOL	USA	Oral Diseases and Disorders Research	000	10	5/24/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2011 ( Subtotal = $503,652 )
2011	2011	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON CENTER	FARMINGTON	CT	06030	CAPITOL	USA	Oral Diseases and Disorders Research	000	10	6/13/2011	NON-COMPETING CONTINUATION	$503,652
														Subtotal = $503,652

Issue Date FY: 2010 ( Subtotal = $623,078 )
2010	2010	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON CENTER	FARMINGTON	CT	06030	CAPITOL	USA	Oral Diseases and Disorders Research	001	9	6/9/2010	NON-COMPETING CONTINUATION	$514,782
2010	2009	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON CENTER	FARMINGTON	CT	06030	CAPITOL	USA	Trans-NIH Recovery Act Research Support	000	8	2/3/2010	SUPPLEMENT FOR EXPANSION	$108,296
														Subtotal = $623,078

Issue Date FY: 2009 ( Subtotal = $611,990 )
2009	2009	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON CENTER	FARMINGTON	CT	06030	CAPITOL	USA	Trans-NIH Recovery Act Research Support	001	8	9/18/2009	SUPPLEMENT FOR EXPANSION	$105,142
2009	2009	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON CENTER	FARMINGTON	CT	06030	CAPITOL	USA	Oral Diseases and Disorders Research	000	8	5/29/2009	NON-COMPETING CONTINUATION	$506,848
														Subtotal = $611,990

Issue Date FY: 2008 ( Subtotal = $401,595 )
2008	2008	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON CENTER	FARMINGTON	CT	06032	CAPITOL	USA	Oral Diseases and Disorders Research	000	7	4/25/2008	COMPETING CONTINUATION	$401,595
														Subtotal = $401,595

Issue Date FY: 2006 ( Subtotal = $318,584 )
2006	2006	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON CENTER	FARMINGTON	CT	06032	CAPITOL	USA	Oral Diseases and Disorders Research	000	6	6/30/2006	NON-COMPETING CONTINUATION	$318,584
														Subtotal = $318,584

Issue Date FY: 2005 ( Subtotal = $290,000 )
2005	2005	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON CENTER	FARMINGTON	CT	06032	CAPITOL	USA	Oral Diseases and Disorders Research	000	5	6/17/2005	NON-COMPETING CONTINUATION	$290,000
														Subtotal = $290,000

Issue Date FY: 2004 ( Subtotal = $290,000 )
2004	2004	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON CENTER	FARMINGTON	CT	06032	CAPITOL	USA	Oral Diseases and Disorders Research	000	4	9/28/2004	COMPETING CONTINUATION	$290,000
														Subtotal = $290,000

Issue Date FY: 2002 ( Subtotal = $184,875 )
2002	2002	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON CENTER	FARMINGTON	CT	06032	CAPITOL	USA	Oral Diseases and Disorders Research	000	3	8/8/2002	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$184,875
														Subtotal = $184,875

Issue Date FY: 2001 ( Subtotal = $217,388 )
2001	2001	COLUMBIA UNIVERSITY, SCHOOL OF ARTS & SCIENCES	106 LOW LIBRARY	NEW YORK-NEW YORK	NY	10027		USA	Oral Diseases and Disorders Research	000	2	7/30/2001	NON-COMPETING CONTINUATION	$217,388
														Subtotal = $217,388

Grand Total All Awards = $9,171,360

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Oral Epithelial Cells, Candida and PMN Activation

Award Number: R01DE013986

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: 05/05/2026

PERIOD OF PERFORMANCE END DATE: 02/28/2031

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