Notice of Special Interest (NOSI): Chronic Inflammation of the Oral Cavity - An Agent for Oral Mucosal Disease
Notice Number:

Key Dates

Release Date:

October 30, 2023

First Available Due Date:
February 05, 2024
Expiration Date:
May 10, 2027

Related Announcements

  • November 25, 2020 - NIDCR Small Grant Program for New Investigators (R03 Clinical Trial Not Allowed). See NOFO PAR-21-084.
  • May 07, 2020 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed). See NOFO PA-20-195.
  • May 05, 2020 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed). See NOFO PA-20-185.

Issued by

National Institute of Dental and Craniofacial Research (NIDCR)


The National Institute of Dental and Craniofacial Research (NIDCR) is issuing this Notice of Special Interest (NOSI) to encourage research studies that investigate the mechanisms of chronic inflammation of the oral cavity, including chronic oral manifestations of systemic diseases. Chronic inflammation of the oral mucosa can create or contribute to serious health conditions within and outside the oral cavity. This announcement encourages studies with a mechanistic focus on chronic inflammation as they relate to onset or progression of dental, oral and craniofacial diseases. 

Multiple inflammatory mechanisms may lead to a state of chronic inflammation within the oral cavity including those initiated by commensal or pathogenic microbiota, or through host immunity and mucosal homeostasis disruption. While it is recognized that oral chronic inflammation is associated with a variety of systemic conditions, the mechanisms by which chronic inflammation then affects the onset and progress of diseases of the oral cavity is less clear. Commensal microbiota are known to affect inflammation and other mechanisms that play a role in carcinogenesis. In the context of plasminogen deficiency, commensal organisms can trigger extravascular fibrin deposition in the oral mucosa, leading to tissue damage and chronic inflammation.Elevated levels of oral Fusobacterium nucleatum are linked to extraoral cancer locations, such as the gut tract. F. nucleatum has also been associated with oral inflammation and poor survival in early-stage HPV-negative tongue cancer.  

Viral infections can amplify or worsen chronic inflammation and can lead to various autoimmune related conditions. Amplified innate and adaptive immune responses observed following antigen exposure support a role for infections driving the immunopathology and acting as environmental risk factors, possibly involving molecular mimicry in immune hyperactivity. This is reported in some individuals following infection with SARS-CoV-2, where some patients develop multiple types of autoantibodies and autoimmune disease. As another example, active Epstein-Barr virus (EBV) infection is selectively associated with ectopic lymphoid structures in the salivary glands of Sjögren Disease patients and appears to contribute to local growth and differentiation of disease-specific autoreactive B cells. Immune responses of treatment-naïve patients diagnosed with Sjögren Disease to an H1N1 influenza vaccine identified a mechanistic basis for the B cell hyperactivity. Chronic inflammation can also be associated with oral mucosal autoimmunity in the absence of viral infection like Crohn’s disease, Lupus, and leukemias can present as chronic oral inflammation.  Chronic oral inflammation can be associated with food intolerance, chronic fungal infection as in erythematous candidiasis, and environmental factors like smoking and alcohol use.

Research Objectives

The oral cavity is the gateway for numerous potential etiopathogenetic factors in different diseases. A growing appreciation of the microbial assemblages associated with healthy oral mucosa, the control of immune tolerance and trained memory presents an opportunity to understand and capitalize on the role of chronic inflammation, in preventing the onset of chronic inflammation such as in cancer and autoimmunity and improving clinical management of disease. Opportunities to expand knowledge on the role in chronic inflammation in the oral cavity and how it relates to onset or progression of oral diseases could address, but are not limited to the following topics: 

  • Understanding mechanisms involved in post-viral chronic inflammation
  • Exploring the relationship of microbially induced chronic inflammation and onset or progression of oral related cancers; role of specific microbes and the understanding of the immune-oncology-microbiome axis
  • Elucidating host-microbe interactions that induce autoreactivity, activating mechanisms such as molecular mimicry, epitope spreading, bystander activation, and immortalization of infected B cells that can lead to autoimmune related illnesses
  • Developing treatments and therapeutic approaches for chronic inflammation focused on functional endpoints in the oral cavity
  • Investigating mechanisms of oral manifestations of chronic inflammation such as oral lichen planus, inflammatory bullous pemphigus, orofacial granulomatosis.

Studies that propose microbial dysbiosis that result as a consequence of disease are discouraged. Clinical observations and other descriptive studies without mechanistic analysis will be considered non-responsive.

Application and Submission Information

This notice applies to due dates on or after February 5, 202 4, and subsequent receipt dates through September 7, 2026. 

Submit applications for this initiative using one of the following notice of funding opportunity (NOFOs) or any reissues of these announcements through the expiration date of this notice.

NOFOTitleFirst Available Due DateExpiration Date
PA-20-185NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)February 5, 2024May 08, 2024
PA-20-195NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)February16, 2024May 08, 2024
PAR-21-084NIDCR Small Grant Program for New Investigators (R03 Clinical Trial Not Allowed)February16,2024September 12, 2024


All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

  • For funding consideration, applicants must include “NOT-DE-23-007” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.


Please direct all inquiries to the Scientific/Research, Peer Review, and Financial/Grants Management contacts in Section VII of the listed notice of funding opportunity.

Scientific/Research Contact(s)

Preethi Chander, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Phone: 301-827-4620

Tamara McNealy, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 202-430-1474

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Gabriel Hidalgo, MBA
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-827-4630