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Age-Related Immunometabolic Dysregulation in Periodontitis Resolution

Award Number: K99DE036617
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/16/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Age-Related Immunometabolic Dysregulation in Periodontitis Resolution - Project Summary/Abstract Periodontal disease is a chronic inflammatory condition and a leading cause of tooth loss, with disease severity and impaired treatment outcomes increasing with age. Successful periodontal therapy depends on effective inflammation resolution, an active biological process required to restore tissue homeostasis. Aging disrupts this process, resulting in persistent inflammation, impaired tissue repair, and alveolar bone loss. Despite growing evidence that immune cell metabolism regulates inflammation resolution and metabolic dysregulation is a hallmark of aging, the metabolic pathways operating within periodontal tissues remain poorly defined. This proposal focuses on polyamines, a class of metabolites critical for immune regulation, whose roles in periodontal inflammation resolution are incompletely understood. Current knowledge of immunometabolic regulation in periodontal disease is largely derived from circulating biomarkers, which do not adequately reflect tissue- or cell- specific metabolic changes at disease sites. To address this gap, this project uses an aging murine model of ligature-induced periodontitis followed by inflammation resolution, enabling direct assessment of polyamine abundance and regulation at both tissue and cellular levels across health, disease, and resolution. Preliminary studies demonstrate that aged mice exhibit impaired collagen deposition and reduced alveolar bone recovery during resolution, accompanied by altered expression of polyamine-metabolizing enzymes and abnormal accumulation of specific polyamines. At the cellular level, aging is associated with increased infiltration of inflammatory macrophages expressing Toll-like receptor 4, which is linked to sustained pro-inflammatory signaling and impaired resolution. These findings support the central hypothesis that aging disrupts polyamine metabolism in macrophages, impairing their pro-resolving function and leading to unresolved inflammation and bone loss. Three integrated aims will: (1) identify the polyamine profiles and their regulatory network in periodontal tissues; (2) demonstrate whether polyamines reprogram pro-resolving functions in macrophages; and (3) evaluate age-associated polyamine influence on inflammation resolution. This K99/R00 award (PAR-25- 333) will provide advanced training in immunometabolism, aging biology, and multi-omics analysis, supporting my transition to research independence. The proposed studies will advance understanding of age-related inflammatory dysregulation in periodontal disease while establishing an independent research trajectory in immunometabolomics and periodontology.


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 = $162,000 )
2026	2026	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Oral Diseases and Disorders Research	000	1	9/17/2026	NEW	$162,000
														Subtotal = $162,000

Grand Total All Awards = $162,000

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Age-Related Immunometabolic Dysregulation in Periodontitis Resolution

Award Number: K99DE036617

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/16/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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