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Principal Investigator: Jacqueline Mays
Organization: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
Fiscal Year: 2024
Award: $1,939,380
Funding agency: National Institute of Dental and Craniofacial Research
Our initial studies have focused on patients who have undergone allogeneic hematopoietic cell transplantation (HCT) as curative therapy primarily for hematological malignancies. Approximately 50% of allogeneic HCT recipients develop chronic Graft-Versus-Host-Disease (cGVHD), a multi-organ autoimmune-like disorder, and the oral cavity (oral mucosa or salivary glands) is affected in a majority of cGVHD patients. While mucosal manifestations are readily evaluable, pathologic changes in salivary glands progress silently from periductal and diffuse lymphocytic infiltrates to destruction of secretory acini and irreversible glandular fibrosis, with severe consequences on oral health and quality of life. Understanding the mechanisms underlying salivary gland destruction and influences of the local oral environment on the immune response may contribute to development of targeted therapies and non-invasive methods for serial screening and treatment of post-transplant patients prior to glandular destruction. We are investigating immune and physiologic causes of oral mucosa and salivary gland dysfunction following allogeneic hematopoietic stem cell transplant using mouse and human models and are conducting clinical trials directed toward advancing cGVHD therapy.
Our recent work has identified immune cell populations in cGVHD-affected oral mucosa and salivary glands and alterations in the local environment of the oral cavity. Work from a multi-center clinical trial (NCT04188912) examined the oral and fecal microbiome longitudinally by analyzing a total of 195 samples via metagenomic sequencing. The onset of oral cGVHD was characterized by an expansion of Streptococcus salivarius and Veillonella parvula in the oral microbiome. Overlap between parent species in the oral and fecal microbiomes suggests that further work may be warranted to examine potential coalescence of bacterial populations in these immunosuppressed patients. Established assays in our lab were recently extended to analyze skin lesions taken from patients exposed to the SARS-CoV-2 virus and affected with pernio or chilblains lesions at acral sites also known as COVID toes for a project that was published this year and identified SARS-CoV-2 viral RNA and a type I interferon signature within pandemic-associated pernio lesions. In a mouse model of cGVHD, we have identified GVHD-like infiltration of specific lymphocyte subsets in the salivary gland accompanied by structural alteration and fibrosis, suggesting that this system could be a powerful tool for mechanistic and interventional laboratory studies focused on cGVHD salivary gland pathogenesis. These studies are ongoing and are contributing to a clear characterization of the pathogenic process of oral cGVHD in the salivary glands and oral mucosa that will lead to identification of additional therapeutic targets. Ongoing clinical trial work includes characterization and sampling of the oral cavity in patients following HCT (NCT03602599) at NIDCR and in conjunction with the NIH interdisciplinary cGVHD group, and a multi-center randomized placebo-controlled trial to treat oral cGVHD using photobiomodulation (NCT05675930) along with collaboration with transplant teams across the NIH Clinical Center to study and care for the oral cavity in the peri- and post-HCT period. In summary, our current scientific investigation has identified microenvironmental changes, specific immune cell populations active in the cGVHD salivary gland, and effector-site immune perturbations that are linked to post-transplant tissue damage. In the past year, we have contributed to work in patient advocacy and education and academic review of cGVHD clinical care for dental, dermatology and transplant care providers.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Acinus organ component><Affect><Allogenic><Assay><Autoimmune><Bioassay><Biological Assay><Buccal Cavity><Buccal Cavity Head and Neck><Buccal Mucosa><COVID-19><COVID-19 exposure><COVID-19 virus><COVID19 virus><CV-19><Cavitas Oris><Cell Body><Cells><Chilblains><Chronic GVHD><Clinical Trials><CoV-2><CoV2><Collaborations><Conduct Clinical Trials><Coronavirus Infectious Disease 2019><Dental Care><Dental Procedure><Dermatology><Development><Diagnosis><Diffuse><Disease><Disorder><Duct><Duct (organ) structure><Dysfunction><Environment><Evaluable><Evaluable Disease><Fibrosis><Functional disorder><Goals><HSC transplantation><Hematologic Cancer><Hematologic Malignancies><Hematologic Neoplasms><Hematological Malignancies><Hematological Neoplasms><Hematological Tumor><Hematopoietic Cancer><Hematopoietic Stem Cell Transplant><Hematopoietic Stem Cell Transplantation><Immune><Immune response><Immunes><Immunobiology><Immunocompromised><Immunocompromised Host><Immunocompromised Patient><Immunological response><Immunophysiology><Immunosuppressed Host><Infiltration><Interferon Type I><Intervention><Intervention Strategies><Investigation><Laboratory Study><Lesion><Link><Lymphocyte Subpopulations><Lymphocyte Subset><Lymphocytic Infiltrate><M gazogenes><M lactilyticus><M. gazogenes><M. lactilyticus><M.gazogenes><M.lactilyticus><Malignant Hematologic Neoplasm><Methods><Micrococcus gazogenes><Micrococcus gazogenes alcalescens anaerobius><Micrococcus lactilyticus><Mouth><Mouth Mucosa><Mouth microbiome><Mucosa><Mucosal Tissue><Mucous Membrane><Multi-Institutional Clinical Trial><Multi-center clinical trial><Multi-site clinical trial><Multicenter clinical trial><Multisite clinical trial><NIDCR><NIDR><NIH><National Institute of Dental Research><National Institute of Dental and Craniofacial Research><National Institutes of Health><Oral><Oral Examination><Oral Mucosa><Oral cavity><Oral health><Oral mucous membrane structure><Organ><Parents><Pathogenesis><Pathogenicity><Pathologic><Patient Education><Patient Instruction><Patient Training><Patient advocacy><Patients><Physiologic><Physiological><Physiopathology><Population><Process><Publishing><QOL><Quality of life><Research><S parvulus><S salivarius><S. parvulus><S. salivarius><S.parvulus><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 exposure><SARS-CoV2><SARS-CoV2 exposure><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Salivary Gland Diseases><Salivary Glands><Salivary Glands Head and Neck><Sampling><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 exposure><Severe acute respiratory syndrome related corona virus 2><Site><Staphylococcus parvulus><Streptococcus salivarius><System><Tissue Transplantation><Toes><Translating><Transplant Recipients><Transplantation><United States National Institutes of Health><V alcalescens><V gazogenes><V parvula><V. alcalescens><V. gazogenes><V. parvula><V.alcalescens><V.gazogenes><V.parvula><Veillonella alcalescens><Veillonella gazogenes><Veillonella parvula><Virus><Work><Wuhan coronavirus><academic review><acinus><analyzing longitudinal><care providers><chronic graft versus host disease><chronic graft vs host disease><chronic graft vs. host disease><clinical care><clinical center><coronavirus disease 2019><coronavirus disease 2019 exposure><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 virus><coronavirus infectious disease-19><curative intervention><curative therapeutic><curative therapy><curative treatments><dental health><dental service><developmental><exposure to COVID-19><exposure to SARS-CoV-2><exposure to SARS-CoV2><exposure to Severe acute respiratory syndrome coronavirus 2><exposure to coronavirus disease 2019><fecal microbiome><hCoV19><hematopoietic cell transplantation><hematopoietic cellular transplantation><hematopoietic progenitor cell transplantation><host response><human model><immune system response><immunoresponse><immunosuppressed patient><interventional strategy><longitudinal analysis><metagenome sequencing><metagenomic sequencing><model of human><mouse model><murine model><nCoV2><oral care><oral microbiome><oral mucosae><oral mucosal><pandemic><pandemic disease><parent><pathophysiology><photobiomodulation><post-transplant><post-transplantation><posttransplant><posttransplantation><randomized placebo control trial><randomized placebo controlled trial><salivary disorder><salivary gland disorder><screening><screenings><skin lesion><stool microbiome><stool-associated microbiome><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><therapeutic target><tool><transplant><transplant patient><viral RNA><virus RNA>