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Roles of neutrophil-sensory neuron interactions in dental pulp inflammation and pain

Award Number: K99DE033421
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 03/01/2024
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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Roles of neutrophil-sensory neuron interactions in dental pulp inflammation and pain - Project Summary/Abstract Pulpitis is a painful disease of the dental pulp tissue, which is treated by expensive and invasive dental procedures such as root canal treatments and tooth extractions. A limited understanding of the intermingling mechanisms of inflammation and pain involving the innate immune response and the dense innervation of the pulp tissue jointly, precludes the precise application of conservative treatments and the development of novel pain management strategies. In this project, the principal investigator will focus on the roles of neutrophils in nerve injury and pain during pulpitis, and how nociceptive neurons modulate innate immune response. Moreover, she proposes to study neuro-immune interactions during pulpitis not only limited within the pulp tissue but in the pulp-periodontium complex where these two neighboring tissues are neuroanatomically connected. The central hypothesis of the study is that during pulpitis, inflammation is present in the pulp and also in the periodontium, and it is modulated by nociceptive neurons, and driven by neutrophils which regulate sensory and pain outcomes. In Aim 1 of the K99 phase, Dr. Erdogan will identify neutrophil-driven nerve injury and pain outcomes during pulpitis by using different clinically informed animal models of pulpitis, perform pharmacological manipulations of neutrophils, use tissue-clearing and whole-mount imaging, single-nuclei RNA sequencing and in-situ hybridization to detect anatomical and transcriptional changes of neurons. She will also use evoked and non- evoked pain behavior assays. In Aim 2 of the K99 phase, Dr. Erdogan will identify the impact of silencing nociceptive neurons on neutrophil recruitment and responses in the pulp tissue during pulpitis. She will use chemogenetic and DREADD-based approaches to silence certain subsets of neurons and perform flow cytometry and sensitive ELISA-based assays to assess innate immune responses. In the R00 phase of the award, in Aim 3, Dr. Erdogan will identify the mechanisms and unique signatures of inflammation in the neighboring periodontium during pulpitis, focusing on neuronal-driven inflammation, by using in-vivo dental pulp neuron activation models and pulpitis models. She will investigate neurogenic inflammatory mechanisms, and outcomes and establish the framework and understanding of how the neighboring periodontium anticipates and responds to diseases affecting the pulp tissue. During the K99 mentored phase, Dr. Erdogan will learn the skills and cutting-edge techniques necessary to accomplish the proposed research under the guidance of expert scientists Dr. Isaac M. Chiu (primary mentor), Dr. Jennifer L. Gibbs (co-mentor), Dr. William Renthal and Dr. Thomas Van Dyke (collaborators) who collectively have an extensive track record of training scientists and dentist-scientists. The proposed scientific and career development training during the K99 phase of the award will support Dr. Erdogan in her transition to being an independent dentist-scientist.


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 = $0 )
2026	2025	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Oral Diseases and Disorders Research	000	2	12/2/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $120,558 )
2025	2025	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Oral Diseases and Disorders Research	000	2	3/5/2025	NON-COMPETING CONTINUATION	$120,558
														Subtotal = $120,558

Issue Date FY: 2024 ( Subtotal = $120,558 )
2024	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Oral Diseases and Disorders Research	000	1	2/14/2024	NEW	$120,558
														Subtotal = $120,558

Grand Total All Awards = $241,116

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Roles of neutrophil-sensory neuron interactions in dental pulp inflammation and pain

Award Number: K99DE033421

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 03/01/2024

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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