The Oklahoma ACE, comprised of 26 investigators from diverse clinical and research backgrounds, partners nationally and internationally known, Oklahoma-based clinical and basic science investigators to collaboratively study diverse aspects of autoimmunity. The central theme of our Oklahoma ACE Basic Science Program is to partner basic investigation with clinical lines of inquiry to understand the biology of autoimmune disease flares to aid diagnosis, clinical trial design, therapeutic development and treatment selection to improve the lives of patients with autoimmune diseases. Through exploration of heightened immune dysregulation closely associated with disease flares at the systemic, cellular and molecular levels, we will identify biologic mechanisms which are important in disease pathogenesis and in clinical disease activity. Our principal project focuses on novel mechanisms of gene expression regulation of TNFAIP3, a potent negative regulator of NF-kB signaling, which has been identified and confirmed as a risk gene for a number of waxing and waning autoimmune diseases. The collaborative project tests hypotheses of regulatory, inflammatory and TNFR exosomal dysregulated immune process association with impending SLE disease flare, as well as provides novel collaborative opportunities to test additional mechanisms of SLE disease activity and to test confirmed flare mechanisms across other autoimmune diseases. Our pilot project will assess mechanisms of multiple sclerosis relapse by examining unique clonal representation through T cell receptor characterization and expansion in CSF and peripheral blood. The overarching goals of our Oklahoma ACE are to understand the pathogenic mechanisms of autoimmune disease flares within and across autoimmune disorders.
Our aims foster integration of a multidisciplinary group to study fundamental aspects of autoimmunity, fortify and expand this nucleus through common educational forums, cultivate and expand ACE collaborative scientific interactions, provide the administrative foundation to Oklahoma ACE investigators, and expand integration of our local expertise in genetics, genomics, epigenetics, various aspects of immunology, analytic methodologies and novel clinical trial design to the national ACE Network.
Despite advances in autoimmune disease research, little is known about the mechanisms of disease flares. These flares often result in increased disease severity and decreased quality of life for autoimmune disease patients. Our Oklahoma ACE partners basic science and clinical investigators to examine the pathogenic mechanisms of autoimmune disease flares within and across autoimmune disorders.
|St Clair, E William; Baer, Alan N; Wei, Chungwen et al. (2018) Clinical Efficacy and Safety of Baminercept, a Lymphotoxin ? Receptor Fusion Protein, in Primary Sjögren's Syndrome: Results From a Phase II Randomized, Double-Blind, Placebo-Controlled Trial. Arthritis Rheumatol 70:1470-1480|
|Koelsch, Kristi A; Cavett, Joshua; Smith, Kenneth et al. (2018) Evidence of Alternative Modes of B Cell Activation Involving Acquired Fab Regions of N-Glycosylation in Antibody-Secreting Cells Infiltrating the Labial Salivary Glands of Patients With Sjögren's Syndrome. Arthritis Rheumatol 70:1102-1113|
|Hinks, Anne; Marion, Miranda C; Cobb, Joanna et al. (2018) Brief Report: The Genetic Profile of Rheumatoid Factor-Positive Polyarticular Juvenile Idiopathic Arthritis Resembles That of Adult Rheumatoid Arthritis. Arthritis Rheumatol 70:957-962|
|Pelikan, Richard C; Kelly, Jennifer A; Fu, Yao et al. (2018) Enhancer histone-QTLs are enriched on autoimmune risk haplotypes and influence gene expression within chromatin networks. Nat Commun 9:2905|
|Patel, Zubin; Lu, Xiaoming; Miller, Daniel et al. (2018) A plausibly causal functional lupus-associated risk variant in the STAT1-STAT4 locus. Hum Mol Genet :|
|Kheir, Joseph M; Guthridge, Carla J; Johnston, Jonathon R et al. (2018) Unique clinical characteristics, autoantibodies and medication use in Native American patients with systemic lupus erythematosus. Lupus Sci Med 5:e000247|
|Young, K A; Munroe, M E; Harley, J B et al. (2018) Less than 7 hours of sleep per night is associated with transitioning to systemic lupus erythematosus. Lupus 27:1524-1531|
|Jog, Neelakshi R; Chakravarty, Eliza F; Guthridge, Joel M et al. (2018) Epstein Barr Virus Interleukin 10 Suppresses Anti-inflammatory Phenotype in Human Monocytes. Front Immunol 9:2198|
|Fu, Yao; Tessneer, Kandice L; Li, Chuang et al. (2018) From association to mechanism in complex disease genetics: the role of the 3D genome. Arthritis Res Ther 20:216|
|Hanscombe, Ken B; Morris, David L; Noble, Janelle A et al. (2018) Genetic fine mapping of systemic lupus erythematosus MHC associations in Europeans and African Americans. Hum Mol Genet 27:3813-3824|
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