A5007705938- Systemic Lupus Erythematosus Research
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Ocular Diseases and Behçet’s Syndrome
- Vasculitis and related conditions
- Cancer-related molecular mechanisms research
- Atherosclerosis and Cardiovascular Diseases
- Inflammasome and immune disorders
- Epigenetics and DNA Methylation
- Systemic Sclerosis and Related Diseases
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Hippo pathway signaling and YAP/TAZ
- interferon and immune responses
- Diabetes and associated disorders
- Autoimmune and Inflammatory Disorders Research
- Otitis Media and Relapsing Polychondritis
- Blood disorders and treatments
- Rheumatoid Arthritis Research and Therapies
- Reproductive System and Pregnancy
- Liver Diseases and Immunity
- RNA modifications and cancer
- Mast cells and histamine
- COVID-19 Clinical Research Studies
- Immune cells in cancer
- Monoclonal and Polyclonal Antibodies Research
University of Michigan
2014-2023
University of Pittsburgh
2020-2023
Children's Hospital of Pittsburgh
2020-2021
Michigan United
2020-2021
University of California, Los Angeles
2019
Universidad de Granada
2017
Instituto de Parasitología y Biomedicina "López - Neyra"
2017
Clinical Research Consortium
2017
United States Department of Veterans Affairs
2016
Virginia Commonwealth University
2016
Primary Sjögren's syndrome (SS) is a systemic autoimmune disease with incompletely understood etiology. This study was undertaken to investigate the role of epigenetic dysregulation in pathogenesis primary SS.A genome-wide DNA methylation performed naive CD4+ T cells from 11 patients SS compared age-, sex-, and ethnicity-matched healthy controls. Cytosine quantified using Illumina Infinium HumanMethylation450 BeadChip array, data were validated bisulfite sequencing.Genome-wide analyses...
<h3>Background</h3> The aetiology of systemic sclerosis (SSc) is not clear, but there an emerging evidence gene-specific epigenetic dysregulation in the pathogenesis SSc. <h3>Methods</h3> We performed a genome-wide DNA methylation study dermal fibroblasts six diffuse cutaneous SSc (dSSc) patients, limited (lSSc) patients compared with 12 age-matched, sex-matched and ethnicity-matched healthy controls. Cytosine was quantified more than 485 000 sites across genome. Differentially methylated...
Objective Systemic lupus erythematosus (SLE) is a relapsing autoimmune disease that affects multiple organ systems. T cells play an important role in the pathogenesis of lupus; however, early cell events triggering flares are incompletely understood. This study was undertaken to examine DNA methylation naive CD4+ from patients determine if epigenetic remodeling event flares. Methods A total 74 with SLE Disease Activity Index score 0–18 were included. Naive isolated peripheral blood samples,...
Objective Takayasu arteritis is a rare large vessel vasculitis with incompletely understood etiology. This study was undertaken to perform the first unbiased genome‐wide association analysis of arteritis. Methods Two independent cohorts patients from Turkey and North America were included in our study. The Turkish cohort consisted 559 489 controls, American 134 1,047 controls European ancestry. Genotyping performed using Omni1‐Quad Omni2.5 genotyping arrays. data subjected rigorous quality...
Antiphospholipid antibodies, present in one-third of lupus patients, increase the risk thrombosis. We recently reported a key role for neutrophils - neutrophil extracellular traps (NETs), particular thrombotic events that define antiphospholipid syndrome (APS). To further elucidate APS, we performed comprehensive transcriptome analysis isolated from patients with primary APS. Moreover, APS-associated venous thrombosis was modeled by treating mice IgG prepared APS followed partial restriction...
Significance The key epigenetic regulator EZH2 plays a central role in fibrosis and abnormal angiogenesis scleroderma. EZH2-target genes mediating profibrotic antiangiogenic effects scleroderma patients have been identified characterized. Inhibiting by repurposing already-existing inhibitors currently being trialed cancer might provide therapeutic approach to
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterised by heterogeneous clinical manifestations, autoantibody production and epigenetic dysregulation in T cells. We sought to investigate the contribution development of cutaneous manifestations SLE.We performed genome-wide DNA methylation analyses patients with SLE stratified history malar rash, discoid rash or neither manifestation, age, sex ethnicity matched healthy controls. differentially methylated regions...
The pathogenesis of Behçet's disease (BD), an inflammatory with multisystem involvement, remains poorly understood. This study was undertaken to investigate whether there are DNA methylation abnormalities in BD that might contribute the disease.We examined genome-wide patterns monocytes and CD4+ T cells from 16 male patients untreated age, sex, ethnicity-matched healthy controls. Additional samples were collected 12 same after treatment achievement remission. Genome-wide assessed using...
While diffuse alveolar haemorrhage (DAH) is recognised as a life-threatening complication of systemic lupus erythematosus (SLE), little known about its risk factors and response to treatment. We describe 22 cases DAH in US cohort approximately 1000 patients, compare them 66 controls from the same outpatient cohort.We captured variables pertaining diagnoses SLE secondary antiphospholipid syndrome (APS), analysed by univariate testing. Those with p values <0.05 were then further considered...
To investigate the inflammatory response in giant cell arteritis (GCA) by characterising DNA methylation pattern within temporal artery microenvironment.Twelve patients with non-equivocal histological evidence for GCA and 12 age-matched, sex-matched ethnicity-matched controls normal biopsies were studied. was extracted from affected portions of tissue histologically confirmed arteries controls. Genome-wide status evaluated using Illumina Infinium HumanMethylation450 BeadChip Array....
Many autoimmune diseases are more frequent in females than males humans and their mouse models, sex differences immune responses have been shown. Despite extensive studies of hormones, mechanisms underlying these remain unclear. Here, we focused on chromosomes using the "four core genotypes" model C57BL/6 mice discovered that transcriptomes both autoantigen anti-CD3/CD28 stimulated CD4+ T lymphocytes showed higher expression a cluster 5 X genes when derived from XY as compared to XX mice. We...
Significance This study identifies a mechanistic basis for the enigmatic, long-observed interaction between rheumatoid arthritis shared epitope (SE)—the most significant genetic risk factor in this disease—and exposure to environmental pollutants, such as cigarette smoke. Specifically, we show that SE, acting signal transduction ligand, cooperates with aryl hydrocarbon receptor-activated pathway, and together facilitate cellular events culminate inflammation bone destruction experimental...
EZH2 is an epigenetic regulator that mediates H3K27 trimethylation (H3K27me3) and modulates DNA methylation. The aim of this study was to characterize the role in CD4+ T cells pathogenesis systemic lupus erythematosus.EZH2 expression levels were determined isolated from patients healthy controls. effects overexpression evaluated using a genome-wide methylation approach. Gene profiles microRNAs (miRNAs) assessed by quantitative polymerase chain reaction, while protein examined Western...
Previous studies have shown that differential DNA methylation is associated with SLE susceptibility. How affects the clinical heterogeneity of has not been fully defined. We conducted this study to identify differentially methylated CpG sites nephritis among women SLE.The status 428 229 across genome was characterised for peripheral blood cells from 322 European descent SLE, 80 whom had lupus nephritis, using Illumina HumanMethylation450 BeadChip. Multivariable linear regression adjusting...
Aim: We sought to define age-associated DNA methylation changes in naive CD4+ T cells. Materials & methods: Naive cells were collected from 74 healthy individuals (age 19–66 years), and age-related characterized. Results: identified 11,431 CpG sites, 57% of which hypermethylated with age. Hypermethylated sites enriched islands repressive transcription factor binding while hypomethylated showed cell specific enrichment active enhancers marked by H3K27ac H3K4me1. Our data emphasize...
Genetic and epigenetic variability contributes to the susceptibility pathogenesis of autoimmune diseases. T cells play an important role in several conditions, including lupus, which is more common severe people African descent. To investigate inherent differences between ethnicities, we characterized genome-wide DNA methylation patterns naïve CD4+ healthy African-Americans European-Americans, then confirmed our findings lupus patients.Impressive ethnicity-specific clustering profiling was...