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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

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Concept Gene Expression Regulation
Academic Article Chemokine gene activation in human bone marrow-derived osteoblasts following exposure to particulate wear debris.
Academic Article The role of fibroblasts and fibroblast-derived factors in periprosthetic osteolysis.
Academic Article Anti-CD44 treatment abrogates tissue oedema and leukocyte infiltration in murine arthritis.
Academic Article Particulate wear debris activates protein tyrosine kinases and nuclear factor kappaB, which down-regulates type I collagen synthesis in human osteoblasts.
Academic Article The effects of particulate wear debris, cytokines, and growth factors on the functions of MG-63 osteoblasts.
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 Cutting edge: regulation of T cell activation threshold by CD28 costimulation through targeting Cbl-b for ubiquitination.
Academic Article IL-4 potentiates activated T cell apoptosis via an IL-2-dependent mechanism.
Academic Article Identification and quantification of disease-related gene clusters.
Academic Article Proteoglycan-induced arthritis: immune regulation, cellular mechanisms, and genetics.
Academic Article Gene expression profiling in murine autoimmune arthritis during the initiation and progression of joint inflammation.
Academic Article Interleukin-4 regulates proteoglycan-induced arthritis by specifically suppressing the innate immune response.
Academic Article Two loci on chromosome 15 control experimentally induced arthritis through the differential regulation of IL-6 and lymphocyte proliferation.
Academic Article Osteoarthritis-like damage of cartilage in the temporomandibular joints in mice with autoimmune inflammatory arthritis.
Academic Article Differentially expressed epigenome modifiers, including aurora kinases A and B, in immune cells in rheumatoid arthritis in humans and mouse models.
Academic Article A differential gene expression study: Ptpn6 (SHP-1)-insufficiency leads to neutrophilic dermatosis-like disease (NDLD) in mice.
Academic Article Transcription factor Zbtb38 downregulates the expression of anti-inflammatory IL1r2 in mouse model of rheumatoid arthritis.

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