A5072814890- Inflammasome and immune disorders
- interferon and immune responses
- Immune Response and Inflammation
- IL-33, ST2, and ILC Pathways
- Ubiquitin and proteasome pathways
- Lipoproteins and Cardiovascular Health
- Autoimmune and Inflammatory Disorders Research
- S100 Proteins and Annexins
- Ion Channels and Receptors
- Heme Oxygenase-1 and Carbon Monoxide
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Adenosine and Purinergic Signaling
- Erythrocyte Function and Pathophysiology
- NF-κB Signaling Pathways
- Circular RNAs in diseases
- Protein Kinase Regulation and GTPase Signaling
- Biomarkers in Disease Mechanisms
- Cholesterol and Lipid Metabolism
- Circadian rhythm and melatonin
- Endoplasmic Reticulum Stress and Disease
- Lysosomal Storage Disorders Research
- Protein Tyrosine Phosphatases
- Muscle Physiology and Disorders
- RNA and protein synthesis mechanisms
- Genetic and Kidney Cyst Diseases
National Human Genome Research Institute
2014-2024
National Institutes of Health
2012-2024
Jeju National University
2024
National Institute of Arthritis and Musculoskeletal and Skin Diseases
1999-2013
Medical Genetics Center
2012
Macquarie University
2005
National Cancer Institute
2001
Seoul National University
1993-2000
Adult-onset inflammatory syndromes often manifest with overlapping clinical features. Variants in ubiquitin-related genes, previously implicated autoinflammatory disease, may define new disorders.We analyzed peripheral-blood exome sequence data independent of phenotype and inheritance pattern to identify deleterious mutations genes. Sanger sequencing, immunoblotting, immunohistochemical testing, flow cytometry, transcriptome cytokine profiling were performed. CRISPR-Cas9-edited zebrafish...
We observed a syndrome of intermittent fevers, early-onset lacunar strokes and other neurovascular manifestations, livedoid rash, hepatosplenomegaly, systemic vasculopathy in three unrelated patients. suspected genetic cause because the disorder presented early childhood.We performed whole-exome sequencing initial patients their unaffected parents candidate-gene with similar phenotype, as well two young siblings polyarteritis nodosa one patient small-vessel vasculitis. Enzyme assays,...
Abstract Objective Neonatal‐onset multisystem inflammatory disease (NOMID; also known as chronic infantile neurologic, cutaneous, articular [CINCA] syndrome) is characterized by fever, meningitis, uveitis, sensorineural hearing loss, urticarial skin rash, and a characteristic deforming arthropathy. We investigated whether patients with this disorder have mutations in CIAS1 , the gene which causes Muckle‐Wells syndrome familial cold autoinflammatory syndrome, two dominantly inherited...
Familial Mediterranean fever (FMF) is a recessively inherited autoinflammatory disorder with high carrier frequencies in the Middle East. Pyrin, protein mutated FMF, regulates caspase-1 activation and consequently IL-1beta production through cognate interaction of its N-terminal PYRIN motif ASC adaptor protein. However, preponderance mutations reside pyrin's C-terminal B30.2 domain. Here we demonstrate direct this domain caspase-1. In lysates from cells not expressing ASC, reciprocal GST...
Autosomal recessive mutations in proteasome subunit β 8 (PSMB8), which encodes the inducible β5i, cause immune-dysregulatory disease chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE), is classified as a proteasome-associated autoinflammatory syndrome (PRAAS). Here, we identified 4 genes, PSMA3 (encodes α7), PSMB4 β7), PSMB9 β1i), maturation protein (POMP), that have not been previously associated 1 mutation PSMB8 has reported. One patient was...
Systemic autoinflammatory diseases are caused by mutations in genes that function innate immunity. Here, we report an disease loss-of-function OTULIN (FAM105B), encoding a deubiquitinase with linear linkage specificity. We identified two missense and one frameshift Pakistani Turkish families four affected patients. Patients presented neonatal-onset fever, neutrophilic dermatitis/panniculitis, failure to thrive, but without obvious primary immunodeficiency. HEK293 cells transfected mutated...
Abstract Objective Familial Mediterranean fever (FMF) has traditionally been considered an autosomal‐recessive disease; however, it observed that a substantial number of patients with clinical FMF possess only 1 demonstrable MEFV mutation. The purpose this study was to perform extensive search for second mutation in 46 diagnosed clinically as having and carrying high‐penetrance Methods other candidate genes were sequenced by standard capillary electrophoresis. In 10 patients, the entire...
TNF, acting through p55 tumor necrosis factor receptor 1 (TNFR1), contributes to the pathogenesis of many inflammatory diseases. TNFR-associated periodic syndrome (TRAPS, OMIM 142680) is an autosomal dominant autoinflammatory disorder characterized by prolonged attacks fevers, peritonitis, and soft tissue inflammation. TRAPS caused missense mutations in extracellular domain TNFR1 that affect folding trafficking. These lead loss normal function rather than gain function, thus enigma. Here we...
Abstract PGE2 is a potent lipid mediator involved in maintaining homeostasis but also promotion of acute inflammation or immune suppression chronic and cancer. Nucleotide-binding domain, leucine-rich repeat–containing protein (NLR)P3 inflammasome plays an important role host defense. Uncontrolled activation the NLRP3 inflammasome, owing to mutations gene, causes cryopyrin-associated periodic syndromes. In this study, we showed that inhibited by human primary monocyte-derived macrophages....
Gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase, is characterized by presence glucosylcer-amide macrophages, accumulation glucosylceramide in lysosomes and secretion inflammatory cytokines. However, connection between this storage inflammation not clear. Studying macrophages derived from peripheral monocytes patients with type 1 disease genotype N370S/N370S, we confirmed an increased interleukins IL-1β IL-6. In addition, found that activation inflammasome, a...
Significance This study identifies a mutation in the NLRP3 gene that causes sensorineural hearing loss human patients. encodes protein important for innate immunity, secretion of potent cytokine IL-1β, and inflammation. The three affected members one family improved or completely resolved after treatment with IL-1β blockade therapy. shows mouse Nlrp3 is expressed immune macrophage-like cells throughout inner ear, which can be activated to release IL-1β. These observations suggest mutations...