京都大学 · 生化学・遺伝学・分子生物学
Kazushi Izawa教授の研究室は、主に自己免疫疾患や炎症性疾患の分子メカニズムを解明することを目的としています。特に、STING経路の異常やIFN-1シグネチャーの上昇に関連する遺伝的変異(例:COPA変異、NLRP3 somatic mosaicism)が、自己炎症性疾患や肺疾患を引き起こすメカニズムを解析しています。また、T細胞のコ-stimulation(CD27/CD70)がウイルス感染に与える影響や、自己免疫疾患の病態におけるT細胞機能異常の解明にも取り組んでいます。
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We provide vector-like gauge theories which break supersymmetry dynamically.
Epstein-Barr virus (EBV) infection in humans is a major trigger of malignant and nonmalignant B cell proliferations. CD27 is a co-stimulatory molecule of T cells, and inherited CD27 deficiency is characterized by high susceptibility to EBV infection, though the underlying pathological mechanisms have not yet been identified. In this study, we report a patient suffering from recurrent EBV-induced B cell proliferations including Hodgkin's lymphoma because of a deficiency in CD70, the ligand of CD2
Chronic infantile neurological cutaneous and articular syndrome (CINCA), also known as neonatal-onset multisystem inflammatory disease (NOMID), is a dominantly inherited systemic autoinflammatory disease and is caused by a heterozygous germline gain-of-function mutation in the NLRP3 gene. We recently found a high incidence of NLRP3 somatic mosaicism in apparently mutation-negative CINCA/NOMID patients using subcloning and subsequent capillary DNA sequencing. It is important to rapidly diagnose s
Nonlinear gauge theory is a gauge theory based on a nonlinear Lie algebra (finite W algebra) or a Poisson algebra, which yields a canonical star product for deformation quantization as a correlator on a disk. We pursue nontrivial deformation of topological gauge theory with conjugate scalars in two dimensions. This leads uniquely to a two-dimensional nonlinear gauge theory, which implies its essential uniqueness. We also consider a possible generalization to higher dimensions.
V242G, a novel COPA variant, was found in 4 patients from one family. In gene-targeted mice with the V242G variant, interstitial lung disease was recapitulated and augmented responses of the STING pathway, leading to an increase in type I IFN production, were demonstrated.
Half of the patients examined in this study, with undifferentiated inflammatory diseases, clinically quiescent A20 haploinsufficiency, or idiopathic pulmonary hemosiderosis, had an elevated type I IFN signature.
This study provides one of the largest epidemiologic data sets for CAPS. Although early initiation of anti-IL-1 treatment with canakinumab is beneficial for improving disease prognosis, some patients do not achieve remission despite a high serum concentration of canakinumab. Moreover, IBD may develop in CAPS after canakinumab treatment.
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