A5038652272- Salivary Gland Disorders and Functions
- RNA Research and Splicing
- Salivary Gland Tumors Diagnosis and Treatment
- RNA regulation and disease
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- Dermatological and COVID-19 studies
- Single-cell and spatial transcriptomics
- Extracellular vesicles in disease
- Oral microbiology and periodontitis research
- Virus-based gene therapy research
- Immune Cell Function and Interaction
- Oral Health Pathology and Treatment
- Protease and Inhibitor Mechanisms
- Thyroid Disorders and Treatments
- Galectins and Cancer Biology
- Cancer-related molecular mechanisms research
- Immunotherapy and Immune Responses
- Systemic Lupus Erythematosus Research
- HIV Research and Treatment
- Gut microbiota and health
- Glycosylation and Glycoproteins Research
- Neuroinflammation and Neurodegeneration Mechanisms
National Institute of Dental and Craniofacial Research
2010-2024
National Institutes of Health
2010-2024
Association of American Veterinary Medical Colleges
2022
University of Virginia
2022
University of Miami
2019-2020
Leonardo (United Kingdom)
2019
University of Chile
2003-2018
Despite signs of infection—including taste loss, dry mouth and mucosal lesions such as ulcerations, enanthema macules—the involvement the oral cavity in coronavirus disease 2019 (COVID-19) is poorly understood. To address this, we generated analyzed two single-cell RNA sequencing datasets human minor salivary glands gingiva (9 samples, 13,824 cells), identifying 50 cell clusters. Using integrated normalization annotation, classified 34 unique subpopulations between gingiva. Severe acute...
MicroRNAs (miRs) seem to mediate renal fibrosis in several diseases, with some miRs having profibrotic effects and others opposing effects. Although differential expression of certain has been described lupus nephritis, it is unknown whether contribute or could serve as biomarkers specific histologic manifestations nephritis. Here, we compared miR kidney biopsies from patients nephritis identified miR-150 the most differentially expressed kidneys high chronicity (chronicity index [CI] ≥ 4);...
Disorganization of acinar cell apical microvilli and the presence stromal collagen in lumen suggest that labial salivary gland (LSG) barrier function is impaired patients with Sjögren's syndrome. Tight junctions define polarity regulate paracellular flow ions water, crucial functions cells. This study was undertaken to evaluate expression localization tight junction proteins LSGs from SS determine vitro effects tumor necrosis factor alpha (TNFalpha) interferon-gamma (IFNgamma) on integrity...
Periodontitis affects billions of people worldwide. To address relationships periodontal niche cell types and microbes in periodontitis, we generated an integrated single-cell RNA sequencing (scRNAseq) atlas human periodontium (34-sample, 105918-cell), including sulcular junctional keratinocytes (SK/JKs). SK/JKs displayed altered differentiation states were enriched for effector cytokines periodontitis. Single-cell metagenomics revealed 37 bacterial species with cell-specific tropism....
Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease that associated with inflammation and dysfunction of salivary lacrimal glands. The molecular mechanism(s) underlying this exocrinopathy not known, although the has been viruses, such as Epstein Barr Virus (EBV). We report herein an EBV-specific microRNA (ebv-miR-BART13-3p) significantly elevated in glands (SGs) pSS patients we show it targets stromal interacting molecule 1 (STIM1), primary regulator store-operated Ca(2+) entry...
Sjögren's syndrome (SS) is a systemic autoimmune disease that mainly affects exocrine salivary and lacrimal glands. Local inflammation in the glands thought to trigger glandular dysfunction symptoms of dryness. However, mechanisms underlying these processes are incompletely understood. Our work suggests T cell exosome–derived miR-142-3p as pathogenic driver immunopathology SS. We first document expression patients with SS, both epithelial gland cells within inflammatory infiltrate, but not...
Inflammatory cytokines that signal through the Janus kinases-signal transducer and activator of transcription (JAK-STAT) pathway, especially interferons (IFNs), are implicated in Sjögren's disease (SjD). Although inhibition JAKs is effective other autoimmune diseases, a systematic investigation IFN-JAK-STAT signalling effect JAK inhibitor (JAKi) therapy SjD-affected human tissues has not been fully investigated.
Whole transcriptome RNA variant analyses have shown that adenosine deaminases acting on (ADAR) enzymes modify a large proportion of cellular RNAs, contributing to diversity and cancer evolution. Despite the advances in understanding ADAR function breast cancer, editing functional consequences are not fully addressed. We characterized A G(I) mRNA 81 cell lines, showing increased at 3'UTR exonic regions cells compared immortalized non-malignant lines. In addition, tumors from BRCA TCGA cohort...
ABSTRACT Despite signs of infection, the involvement oral cavity in COVID-19 is poorly understood. To address this, single-cell RNA sequencing data-sets were integrated from human minor salivary glands and gingiva to identify 11 epithelial, 7 mesenchymal, 15 immune cell clusters. Analysis SARS-CoV-2 viral entry factor expression showed enrichment epithelia including ducts acini suprabasal cells mucosae. autopsy tissues confirmed vivo infection mucosa. Saliva SARS-CoV-2-infected individuals...
Tobacco use is one of the main risk factors for Lung Cancer (LC) development. However, about 10–20% those diagnosed with disease are never-smokers. For Non-Small Cell (NSCLC) there clear differences in both clinical presentation and tumor genomic profiles between smokers example, Adenocarcinoma (LUAD) histological subtype never-smokers predominately found young women European, North American, Asian descent. While have been widely examined, usually underrepresented, especially a Latin...
Abstract Objective To determine the effect of matrix metalloproteinase (MMP) activity from labial salivary glands (LSGs) Sjögren's syndrome (SS) patients on proteins extracellular (ECM) that form basal lamina and stroma, to compare this with structural integrity acini ducts as well functionality LSGs. Methods Gelatinase was determined by zymography. The digestion pattern macromolecules detected gel electrophoresis quantified densitometry. evaluated light electron microscopy. Secretory...
Previous findings in labial salivary glands (LSGs) from patients with Sjögren's syndrome (SS) suggest that increased activity and expression of matrix metalloproteinase 9 (MMP-9) MMP-3 trigger the destruction acinar structures these glands. Tissue inhibitors metalloproteinases (TIMPs) tightly control MMP activity, TIMP is an important modulator effects attributed to MMPs. This study was undertaken investigate correlation between balance MMPs/TIMPs LSGs SS degree inflammatory infiltration...
Abstract Objective Acinar cells in the salivary glands of patients with Sjögren's syndrome (SS) display severe alterations anchorage to basal lamina. Bioinformatics analysis BP230 gene sequence has revealed presence CpG islands that might be involved epigenetic control expression, and methylation promotor region may implicated as an mechanism gland damage. Thus, present study was undertaken evaluate protein BP230, well proteins BP180, α6β4 integrin, cytokeratin‐18, for their expression...
BMP6 is a central cytokine in the induction of Sjögren's syndrome–associated (SS-associated) secretory hypofunction. However, upstream initiation leading to production this SS unknown. In study, RNA ISH on salivary gland sections taken from patients with indicated monocytic lineage cells as cellular source BMP6. RNA-Seq data human glands suggested that TLR4 signaling was an regulator BMP6, which confirmed by vitro cell assays and single-cell transcriptomics PBMCs. Further investigation...
Objective To determine the enzymatic activity and cellular localization of matrix metalloproteinases (MMPs) 2, 3, 9 in labial salivary glands from patients with different degrees severity primary Sjögren's syndrome (primary SS). Methods Gelatinase was determined by zymography quantified densitometry. The specificity MMPs using protease inhibitors chelators, as well activators latent forms these enzymes. carried out monoclonal antibodies that recognize their active forms. Results Labial...
<h3>Objectives:</h3> MUC5B contains sulfated and sialylated oligosaccharides that sequester water required for moisturising the oral mucosa. Xerostomia, in patients with Sjögren syndrome, is generally associated reduced quantities, rather than altered properties, of saliva. Here, we determined amount (mRNA protein) as well sulfation levels salivary glands normal or unstimulated flow. Localisation MUC5B, total groups were compared acini basal lamina disorganisation. <h3>Patients methods:</h3>...
Sjögren's syndrome (SS) is an autoimmune sialadenitis with unknown aetiology. Although extensive research implicated abnormal immune response associated lymphocytes, initiating event mediated by salivary gland epithelial cell (SGEC) abnormalities causing activation poorly characterised. Transcriptome studies have suggested alternations in lysosomal function are SS, but a cause and effect linkage has not been established. In this study, we demonstrated that altered lysosome activity SGECs...
Hepatitis C virus (HCV) infection is the most common blood-borne chronic in United States. Chronic lymphocytic sialadenitis and sicca syndrome have been reported HCV infection. Up to 55% of these patients may xerostomia; mechanisms xerostomia salivary gland (SG) hypofunction remain controversial. The objectives this project are establish if associates with SG characterize structural changes saliva composition. Eighteen HCV-infected were evaluated for dysfunction; 6 (patients 1–6) further...
Sjögren's Disease (SjD) is a systemic autoimmune disease without clear etiology or effective therapy. Utilizing unbiased single-cell and spatial transcriptomics to analyze human minor salivary glands in health we developed comprehensive understanding of the cellular landscape healthy how that changes SjD patients. We identified novel seromucous acinar cell types population