- Lung Cancer Research Studies
- CAR-T cell therapy research
- Cancer therapeutics and mechanisms
- Parathyroid Disorders and Treatments
- DNA Repair Mechanisms
- Electron and X-Ray Spectroscopy Techniques
- Immunotherapy and Immune Responses
- Endoplasmic Reticulum Stress and Disease
- Magnesium in Health and Disease
- Bone health and treatments
- Medical Imaging and Pathology Studies
- Genetic Syndromes and Imprinting
- DNA and Nucleic Acid Chemistry
- Monoclonal and Polyclonal Antibodies Research
- Atomic and Molecular Physics
- Complement system in diseases
- Nuclear Physics and Applications
- Galectins and Cancer Biology
- Ultra-Wideband Communications Technology
- Advanced biosensing and bioanalysis techniques
- Fibroblast Growth Factor Research
- Advanced Chemical Physics Studies
- Enzyme Structure and Function
- Autophagy in Disease and Therapy
- Blood groups and transfusion
Shimizu (Japan)
2020-2021
Kyoto University
1997-2021
Tokyo University of Science
2017-2021
Toranomon Hospital
2021
University of Tsukuba
2019-2020
Shizuoka General Hospital
2020
Chugai Pharma (United States)
2017-2020
Tohoku University
2000-2016
The University of Tokyo
2000-2015
RIKEN Advanced Science Institute
2002-2015
A mammalian nucleotide excision repair (NER) factor, the XPC–HR23B complex, can specifically bind to certain DNA lesions and initiate cell-free reaction. Here we describe a detailed analysis of its binding specificity using various substrates, each containing single defined lesion. highly sensitive gel mobility shift assay revealed that binds small bubble structure with or without damaged bases, whereas dual incision takes place only when damage is present in bubble. This evidence...
In response to terminal differentiation signals that enable B cells produce vast quantities of antibodies, a dramatic expansion the secretory pathway and corresponding increase in molecular chaperones folding enzymes aid monitor immunoglobulin synthesis occurs. Recent studies reveal unfolded protein (UPR), which is normally activated by endoplasmic reticulum (ER) stress, plays critical role this process. Although activate all three branches UPR pharmacological inducers pathway, plasma cell...
Dysregulation of the complement system is linked to pathogenesis a variety hematological disorders. Eculizumab, an anti-complement C5 monoclonal antibody, current standard care for paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). However, because high levels in plasma, eculizumab has be administered biweekly by intravenous infusion. By applying recycling technology through pH-dependent binding C5, we generated novel humanized antibody against SKY59,...
Abstract Small-cell lung cancer (SCLC) is an aggressive for which immune checkpoint inhibitors (ICI) have had only limited success. Bispecific T-cell engagers are promising therapeutic alternatives ICI-resistant tumors, but not all patients with SCLC responsive. Herein, to integrate CD137 costimulatory function into a engager format and thereby augment efficacy, we generated CD3/CD137 dual-specific Fab engineered DLL3-targeted trispecific antibody (DLL3 trispecific). The was competitively...
Modulating the complement system is a promising strategy in drug discovery for disorders with uncontrolled activation. Although some of these can be effectively treated an antibody that inhibits C5, high plasma concentration C5 requires huge dosage and frequent intravenous administration. Moreover, conventional anti-C5 cause to accumulate by reducing clearance when forms immune complex (IC) antibody, which salvaged from endosomal vesicles neonatal Fc receptor (FcRn)-mediated recycling. In...
Abstract Myostatin, a member of the transforming growth factor-β superfamily, is an attractive target for muscle disease therapy because its role as negative regulator and strength. Here, we describe novel antibody therapeutic approach that maximizes potential myostatin-targeted therapy. We generated antibody, GYM329, specifically binds latent form myostatin inhibits activation. Additionally, via “sweeping technology”, GYM329 reduces or “sweeps” in plasma. Compared with conventional...
Plasma cells can synthesize and secrete thousands of Ig molecules per second, which are folded assembled in the endoplasmic reticulum (ER) likely to place unusually high demands on resident chaperones folding enzymes. We have discovered a new ER protein (pERp1) that is component BiP chaperone complex. PERp1 substantially up-regulated during B plasma cell differentiation be induced lines by some UPR activators, arguing it represents potentially class conditional targets. In LPS-stimulated...
Abstract The xeroderma pigmentosum group C (XPC) protein complex is a key factor that detects DNA damage and initiates nucleotide excision repair (NER) in mammalian cells. Although biochemical structural studies have elucidated the interaction of XPC with damaged DNA, mechanism its regulation vivo remains to be understood more details. Here, we show undergoes modification by small ubiquitin-related modifier (SUMO) proteins lack this compromises UV-induced photolesions. In absence...
X-linked hypophosphatemic rickets (XLHR) caused by mutations in the PHEX gene is considered to be most frequent cause of fibroblast growth factor 23 (FGF23)-related congenital rickets. In previous studies, were detected 60-70% patients with clinical diagnoses XLHR. This leads question whether current screening methods for are inadequate or there a substantial number other genetic causes We conducted analysis FGF23-related clarify their etiology and evaluate prevalence XLHR among this...