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Topical Vitamin D and Periodontal Disease

Award Number: R01DE028883
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: 04/02/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2031

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Topical Vitamin D and Periodontal Disease - Project Summary Periodontitis is a highly prevalent chronic inflammatory disease that leads to destruction of gingival tissues, periodontal ligament, and alveolar bone, and contributes to systemic inflammatory comorbidities. Despite its clinical significance, current treatments primarily target bacterial biofilms and fail to address the dysregulated host immune response that drives disease progression. There is a critical need for safe and effective host- modulating therapies that restore mucosal homeostasis and promote inflammation resolution. In this competing renewal, we have demonstrated that topical vitamin D—a safe, inexpensive, and readily bioavailable molecule— prevents inflammation and bone loss in a mouse model of ligature-induced periodontitis (LIP). Topical application of vitamin D enhances epithelial barrier function, induces antimicrobial peptides, promotes specialized pro- resolving mediators (SPMs), and shifts the oral microbiome toward a health-associated composition. These findings establish vitamin D as a potent local immunomodulator with potential to prevent and treat periodontitis. The central hypothesis of this renewal is that vitamin D orchestrates coordinated epithelial–immune responses that restore host–microbiome homeostasis and resolve inflammation through transcriptional and epigenetic regulation. We further posit that vitamin D reprograms inflammatory and metabolic pathways within gingival epithelial and immune cell populations to promote pro-resolving and tissue-protective phenotypes. We propose three specific aims: 1) define how microbial metabolites, particularly short-chain fatty acids (SCFAs) produced by periodontal pathogens, modulate vitamin D signaling to regulate epithelial antimicrobial, barrier, and iron homeostasis genes; 2) characterize the mechanisms by which vitamin D regulates innate immune responses in epithelial and immune cells, focusing on transcriptional regulation, cytokine production, and neutrophil function; and 3) define the transcriptomic landscape of gingival tissues in response to topical vitamin D during experimental periodontitis using single-cell RNA sequencing, spatial transcriptomics, and spectral flow cytometry to map vitamin D–responsive pathways across epithelial, stromal, and immune niches. This multi-PI project leverages complementary expertise in epithelial innate immunity and in vivo inflammation and multiomic data integration. The work is innovative in combining topical therapeutic intervention with advanced single-cell and spatial technologies to elucidate the molecular mechanisms of host modulation at cellular resolution. Further, it will demonstrate a positive relationship between pathogenic bacteria and a therapeutic agent. Completion of this project will establish vitamin D as a precision host-modulating therapy for chronic oral inflammation, advancing a new paradigm in periodontal and mucosal immunology that links microbial ecology, epithelial defense, and immune resolution within a unified therapeutic framework.


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 = $661,094 )
2026	2026	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Oral Diseases and Disorders Research	001	6	8/28/2026	COMPETING CONTINUATION	$695,566
2026	2025	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Oral Diseases and Disorders Research	000	5	8/4/2026	NON-COMPETING CONTINUATION	-$34,472
														Subtotal = $661,094

Issue Date FY: 2025 ( Subtotal = $402,569 )
2025	2025	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Oral Diseases and Disorders Research	001	5	5/8/2025	NON-COMPETING CONTINUATION	$40,256
2025	2025	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Oral Diseases and Disorders Research	000	5	3/7/2025	NON-COMPETING CONTINUATION	$362,313
														Subtotal = $402,569

Issue Date FY: 2024 ( Subtotal = $447,550 )
2024	2024	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Oral Diseases and Disorders Research	001	4	6/5/2024	NON-COMPETING CONTINUATION	$36,534
2024	2024	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Oral Diseases and Disorders Research	000	4	3/21/2024	NON-COMPETING CONTINUATION	$411,016
														Subtotal = $447,550

Issue Date FY: 2023 ( Subtotal = $462,257 )
2023	2023	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Oral Diseases and Disorders Research	000	3	3/23/2023	NON-COMPETING CONTINUATION	$462,257
														Subtotal = $462,257

Issue Date FY: 2022 ( Subtotal = $542,008 )
2022	2022	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Oral Diseases and Disorders Research	001	2	4/21/2022	NON-COMPETING CONTINUATION	$49,276
2022	2022	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Oral Diseases and Disorders Research	000	2	3/31/2022	NON-COMPETING CONTINUATION	$492,732
														Subtotal = $542,008

Issue Date FY: 2021 ( Subtotal = $617,672 )
2021	2021	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Oral Diseases and Disorders Research	000	1	4/2/2021	NEW	$617,672
														Subtotal = $617,672

Grand Total All Awards = $3,133,150

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Topical Vitamin D and Periodontal Disease

Award Number: R01DE028883

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: 04/02/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2031

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