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One or more keywords matched the following properties of Glant, Tibor
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overview Originally as a physician, after spending three years in full-time research (Joint Diseases Laboratories, Shriners Hospital, Montreal, Canada and NIH/NIDR Bethesda), I have fundamentally changed my career converting my clinical experience and training to biomedical science. My major research interest during the past 30 years has been autoimmunity and autoimmune regulation of T and B cells in rheumatoid arthritis (RA) and ankylosing spondylitis (AS), and its corresponding animal models. I have generated monoclonal antibodies (mAbs) to cartilage antigenic components, and used these mAbs for immuno-electron microscopic localization of cartilage matrix molecules in aging and diseased cartilages. During the production of mAbs, serendipitously, I (and my immediate colleagues) “discovered” cartilage proteoglycan (PG) aggrecan-induced arthritis (PGIA) in genetically susceptible (arthritis-prone) BALB/c mice. I have had a long-standing interest and commitment to training of medical students for histopathology, and later on scientists and physician-scientists. In addition to mentoring pre- and postdoctoral trainees in my laboratory and faculty members, I was PI of numerous R01, P01 and R21 NIH grants; I was always funded since I moved to the USA. My early research was thymosin-producing epithelioid cells expected to control early T cell selection in mouse embryos and the mechanisms of Wasting syndrome. Simultaneously, I studied cartilage and bone development as well as cartilage repair and bone healing in animal models, and immunogenicity/antigenicity of cartilage and bone non-collagenous macromolecules. This included numerous histochemistry (mostly enzyme and immune histochemistry), biochemical and immunological methods. I was the first to localize proteoglycan (PG) aggrecan and link protein by immune electron microscopy in cartilage tissue, and first described the autoimmune potential of cartilage PG in patients with RA or ankylosing spondylitis. I/we have sequenced the core proteins of mouse and canine cartilage PG aggrecans, and described splice variants of human PG aggrecan. These pioneer studies were repeated and extended in many laboratories. My expertise in bone and cartilage biochemistry and biology was beneficial when I/we have studied the mechanism of aseptic loosening of total joint replacements, which studies then changed the orthopedic term/diagnosis from “cement disease” to “particulate disease”. Submicron-sized wear debris/particulates are phagocytized by macrophages, fibroblasts and osteoblast, trigger these cells to secrete pro-inflammatory cytokines and proteolytic enzymes leading to aseptic bone resorption and loosening of prosthetic device. After I/we described the PG (aggrecan)-induced arthritis (PGIA) in BALB/c mice in 1987, a large number of studies focused on the immune pathomechanism of this model of RA and mapping studies of (auto)epitopes. PGIA model shares similarities with RA as indicated by clinical assessments, laboratory tests, and histopathology of diarthrodial joints. The development of the disease in genetically susceptible mice is based upon the development of cross-reactive immune responses between the immunizing (human) and self (mouse) cartilage PG. The recessive inheritance of disease susceptibility, as in RA, is dictated by both MHC- and non-MHC-associated genes. I/we identified dominant (arthritic) and subdominant epitopes of human and mouse (self) PG, tested the arthritogenic potential of human cartilage PG, and I generated recombinant human G1 domain (a globular domain of PG which carry all arthritogenic epitopes. This model was used to test the efficacy of Leflunomide (component 418). Numerous laboratories use the PGIA model all over the world, and human studies led to the identification of citrullinated PG epitopes in RA patients. A fourth and most recent research direction is the genetic and epigenetic alterations in PGIA model and in RA patients. I/we identified over 25 quantitative trait loci (QTLs) in different genetic combination of F2 mice. A special select direction of these genetic studies was to generate congenic mice (a short resistant DBA2 allele in susceptible BALB/c background). These congenic mice were/are tested for arthritis susceptibility; genomic regions sequenced and mutated genes selected for in vitro and in vivo studies. Eight of these 25 QTL are syntenic with RA genomic risk loci. From these 8 overlapping RA risk loci we have selected mouse chromosomes 2 and 3, which are highly susceptible to arthritis and syntenic with human chromosomes 9 and 1. Mouse/human susceptible regions carry the PTPN22 (mChr3/hChr1) and C5/TRAF1/PHF19 (mChr2/hChr9) RA risk alleles. The mutated genes are studied in vitro and generating and testing gene-deficient mice for arthritis in susceptible BALB/c background, and allele-specific transgenic mice to rescue the gene deficiency-induced defect(s). My Scopus API key: 458a8af4ddad17c0c313a5e8b8454348 My Orcid ID: https://orcid.org/0000-0002-1706-3820 MY NIH COMMONS: TGLANT Research Areas: Autoimmunity, Rheumatoid Arthritis, Ankylosing Spondylitis, Genetics, Periprosthetic osteolysis My Faculty Profile at Rush University Medical Center: https://www.rushu.rush.edu/faculty/tibor-t-glant-md-phd Education: MD, University of Medical School (DOTE) Debrecen, Hungary PhD, University of Medical School (DOTE) Debrecen, Hungary DMsc. Hungarian Academy of Sciences, Budapest, Hungary
One or more keywords matched the following items that are connected to Glant, Tibor
Item TypeName
Concept Adaptor Proteins, Signal Transducing
Concept DNA-Binding Proteins
Concept Heat-Shock Proteins
Concept ADAM Proteins
Concept HSP72 Heat-Shock Proteins
Concept Membrane Transport Proteins
Concept LIM Domain Proteins
Concept Cytoskeletal Proteins
Concept Carrier Proteins
Concept Proto-Oncogene Proteins c-bcl-2
Concept Proto-Oncogene Proteins c-cbl
Concept HSP70 Heat-Shock Proteins
Concept Recombinant Proteins
Concept Neoplasm Proteins
Concept I-kappa B Proteins
Concept Extracellular Matrix Proteins
Concept Intracellular Signaling Peptides and Proteins
Concept Cation Transport Proteins
Concept Nerve Tissue Proteins
Concept Intercellular Signaling Peptides and Proteins
Concept Repressor Proteins
Concept Bone Morphogenetic Proteins
Concept Proteins
Academic Article Cell-mediated and humoral immune responses to cartilage antigenic components.
Academic Article Antigenicity of bone tissue. I. Immunological and immunohistochemical study of non-collagenous proteins of the bovine cortical bone.
Academic Article Serum keratan sulfate--a marker of predisposition to polyarticular osteoarthritis.
Academic Article Epitopes of cartilage core proteins and GAG pattern in human non-Hodgkin lymphoma xenografts.
Academic Article Mapping of arthritogenic/autoimmune epitopes of cartilage aggrecans in proteoglycan-induced arthritis.
Academic Article Large and small proteoglycans of osteoarthritic and rheumatoid articular cartilage.
Academic Article A proteoglycan (aggrecan)-specific T cell hybridoma induces arthritis in BALB/c mice.
Academic Article Interferon-gamma but not granulocyte/macrophage colony-stimulating factor augments proteoglycan presentation by synovial cells and chondrocytes to an autopathogenic T cell hybridoma.
Academic Article Antigen-specific B cells present cartilage proteoglycan (aggrecan) to an autoreactive T cell hybridoma derived from a mouse with proteoglycan-induced arthritis.
Academic Article Complete coding sequence, deduced primary structure, chromosomal localization, and structural analysis of murine aggrecan.
Academic Article Bone resorption activity of particulate-stimulated macrophages.
Academic Article Expression of alternatively spliced epidermal growth factor-like domains in aggrecans of different species. Evidence for a novel module.
Academic Article Substrate specificity of 'elastomucoproteinase': an enzyme which can degrade cartilage aggrecan.
Academic Article Species-specific alternative splicing of the epidermal growth factor-like domain 1 of cartilage aggrecan.
Academic Article Changes in messenger RNA and protein levels of proteoglycans and link protein in human osteoarthritic cartilage samples.
Academic Article Critical roles of glycosaminoglycan side chains of cartilage proteoglycan (aggrecan) in antigen recognition and presentation.
Academic Article Progressive polyarthritis induced in BALB/c mice by aggrecan from normal and osteoarthritic human cartilage.
Academic Article Proteoglycan (aggrecan)-induced arthritis in BALB/c mice is a Th1-type disease regulated by Th2 cytokines.
Academic Article Complex pattern of Th1 and Th2 activation with a preferential increase of autoreactive Th1 cells in BALB/c mice with proteoglycan (aggrecan)-induced arthritis.
Academic Article Spontaneous thymocyte apoptosis is regulated by a mitochondrion-mediated signaling pathway.
Academic Article Down-regulation of procollagen alpha1[I]] messenger RNA by titanium particles correlates with nuclear factor kappaB (NF-kappaB) activation and increased rel A and NF-kappaB1 binding to the collagen promoter.
Academic Article Impaired Fas signaling pathway is involved in defective T cell apoptosis in autoimmune murine arthritis.
Academic Article Anti-inflammatory and chondroprotective effect of TSG-6 (tumor necrosis factor-alpha-stimulated gene-6) in murine models of experimental arthritis.
Academic Article Point of view.
Academic Article Common mutations of ATP7B in Wilson disease patients from Hungary.
Academic Article Th1 and Th2 cytokines regulate proteoglycan-specific autoantibody isotypes and arthritis.
Academic Article T and B cell recovery in arthritis adoptively transferred to SCID mice: antigen-specific activation is required for restoration of autopathogenic CD4+ Th1 cells in a syngeneic system.
Academic Article Continuous nasal administration of antigen is critical to maintain tolerance in adoptively transferred autoimmune arthritis in SCID mice.
Academic Article Cutting edge: regulation of T cell activation threshold by CD28 costimulation through targeting Cbl-b for ubiquitination.
Academic Article Short overview of potential gene therapy approaches in orthopedic spine surgery.
Academic Article TGF beta 1 and biglycan, decorin, and fibromodulin metabolism in canine cartilage.
Academic Article IL-4 potentiates activated T cell apoptosis via an IL-2-dependent mechanism.
Academic Article Impaired cumulus mucification and female sterility in tumor necrosis factor-induced protein-6 deficient mice.
Academic Article Genetic rescue of chondrodysplasia and the perinatal lethal effect of cartilage link protein deficiency.
Academic Article Spontaneous and experimental osteoarthritis in dog: similarities and differences in proteoglycan levels.
Academic Article Differential recognition of altered peptide ligands distinguishes two functionally discordant (arthritogenic and nonarthritogenic) autoreactive T cell hybridoma clones.
Academic Article Induction of arthritis in SCID mice by T cells specific for the "shared epitope" sequence in the G3 domain of human cartilage proteoglycan.
Academic Article Induction of arthritis in HLA-DR4-humanized and HLA-DQ8-humanized mice by human cartilage proteoglycan aggrecan but only in the presence of an appropriate (non-MHC) genetic background.
Academic Article Proteoglycan aggrecan-induced arthritis: a murine autoimmune model of rheumatoid arthritis.
Academic Article Cutting edge: Cbl-b: one of the key molecules tuning CD28- and CTLA-4-mediated T cell costimulation.
Academic Article Genetic control of experimental spondylarthropathy.
Academic Article T-cell recognition of differentially tolerated epitopes of cartilage proteoglycan aggrecan in arthritis.
Academic Article Molecular manipulation with the arthritogenic epitopes of the G1 domain of human cartilage proteoglycan aggrecan.
Academic Article Experimental spondyloarthropathies: animal models of ankylosing spondylitis.
Academic Article Increased arthritis susceptibility in cartilage proteoglycan-specific T cell receptor-transgenic mice.
Academic Article IL-10 is critically involved in mycobacterial HSP70 induced suppression of proteoglycan-induced arthritis.
Academic Article Animals lacking link protein have attenuated perineuronal nets and persistent plasticity.
Academic Article Mutations in the PSTPIP1 gene and aberrant splicing variants in patients with pyoderma gangrenosum.
Academic Article Interferon-? regulates discordant mechanisms of uveitis versus joint and axial disease in a murine model resembling spondylarthritis.
Academic Article T cell receptor (TCR) signal strength controls arthritis severity in proteoglycan-specific TCR transgenic mice.
Academic Article Irreversible heavy chain transfer to hyaluronan oligosaccharides by tumor necrosis factor-stimulated gene-6.
Academic Article Excessive bone formation in a mouse model of ankylosing spondylitis is associated with decreases in Wnt pathway inhibitors.
Academic Article Pharmacogenetics and pharmacogenomics in rheumatology.
Academic Article Treatment of a mouse model of ankylosing spondylitis with exogenous sclerostin has no effect on disease progression.
Academic Article Transcription factor Zbtb38 downregulates the expression of anti-inflammatory IL1r2 in mouse model of rheumatoid arthritis.
Academic Article ZAP-70 Regulates Autoimmune Arthritis via Alterations in T Cell Activation and Apoptosis.
Academic Article Regulation of autoimmune arthritis by the SHP-1 tyrosine phosphatase.
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