A5086007733- Advanced materials and composites
- Aluminum Alloys Composites Properties
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Magnesium Alloys: Properties and Applications
- Advanced ceramic materials synthesis
- Aluminum Alloy Microstructure Properties
- Metal and Thin Film Mechanics
- Microstructure and mechanical properties
- Epigenetics and DNA Methylation
- ATP Synthase and ATPases Research
- CAR-T cell therapy research
- RNA modifications and cancer
- IL-33, ST2, and ILC Pathways
- Cellular and Composite Structures
- Powder Metallurgy Techniques and Materials
- Ion-surface interactions and analysis
- Metal Alloys Wear and Properties
- Photosynthetic Processes and Mechanisms
- Asthma and respiratory diseases
- Diamond and Carbon-based Materials Research
- Metallurgy and Material Forming
- Mitochondrial Function and Pathology
- Cancer, Lipids, and Metabolism
- Cytokine Signaling Pathways and Interactions
Tokai University
2019-2024
National Institute of Advanced Industrial Science and Technology
2014-2023
Institute of Medical Sciences
2021
California Institute of Technology
2017-2021
Osaka University
2005-2020
Center for Systems Biology
2011-2019
Chiba University
2006-2018
Tottori University
2015
Institute of Immunology
2015
Harvard University
2011-2014
We identified a p53 target gene, phosphate-activated mitochondrial glutaminase (GLS2), key enzyme in conversion of glutamine to glutamate, and thereby regulator glutathione (GSH) synthesis energy production. GLS2 expression is induced response DNA damage or oxidative stress p53-dependent manner, associates with the promoter. Elevated facilitates metabolism lowers intracellular reactive oxygen species (ROS) levels, resulting an overall decrease oxidation as determined by measurement 8-OH-dG...
Abstract Glutamine synthase 2 (GLS2) is a key regulator of glutaminolysis and has been previously implicated in activities consistent with tumor suppression. Here we generated Gls2 knockout (KO) mice that develop late-occurring B-cell lymphomas hepatocellular carcinomas (HCC). Further, KO subjected to the hepatocarcinogenic Stelic Animal Model (STAM) protocol produce larger HCC tumors than seen wild-type (WT) mice. GLS2 shown promote ferroptosis, form cell death characterized by...
Memory T-helper (Th) lymphocytes are crucial for the maintenance of acquired immunity to eliminate infectious pathogens. We have previously demonstrated that most memory Th reside and rest on stromal niches bone marrow (BM). Little is known, however, regarding molecular basis generation BM lymphocytes. Here we show CD69-deficient effector CD4 T fail relocate into persist in therefore differentiate cells. Consequently, cells facilitate production high-affinity antibodies long-lived plasma...
GATA3 expression is essential for type-2 helper T (Th2) cell differentiation. GATA3-mediated chromatin remodeling at the Th2 cytokine gene loci, including Th2-specific long range histone hyperacetylation of interleukin (IL)-13/IL-4 occurs in developing cells. However, little known about role GATA3, if any, maintenance established remodeled loci. Here, we a Cre/LoxP-based site-specific recombination system cultured CD4 cells using unique adenovirus-mediated transfer technique. This allowed us...
The maintenance of memory T cells is central to the establishment immunological memory, although molecular details process are poorly understood. In absence polycomb group (PcG) gene Bmi1, number CD4+ helper (Th)1/Th2 was reduced significantly. Enhanced cell death Bmi1−/− Th2 observed both in vivo and vitro. Among various proapoptotic genes that regulated by expression BH3-only protein Noxa increased effector Th1/Th2 cells. generation restored deletion Noxa, but not Ink4a Arf. Direct binding...
Polycomb group (PcG) and trithorax (TrxG) complexes exert opposing effects on the maintenance of transcriptional status developmentally regulated Hox genes. In this study, we show that activation STAT6 induces displacement PcG complex by TrxG at upstream region gene encoding GATA3, a transcription factor essential for T helper type 2 (Th2) cell differentiation. Once Th2 cells differentiate, associated with component Menin binds to whole GATA3 locus, binding is required long-term expression...
T-cell development from hematopoietic progenitors depends on multiple transcription factors, mobilized and modulated by intrathymic Notch signaling. Key aspects of specification network architecture have been illuminated through recent reports defining roles factors PU.1, GATA-3, E2A, their interactions with signaling, Runx1, TCF-1, Hes1, providing bases for a comprehensively updated model the gene regulatory presented herein. However, role lineage commitment factor Bcl11b has unclear. We...
GATA binding protein 3 (Gata3) is a family transcription factor that controls differentiation of naïve CD4 T cells into helper 2 (Th2) cells. However, it unknown how Gata3 simultaneously activates Th2-specific genes while repressing those other Th lineages. Here we show chromodomain helicase DNA-binding 4 (Chd4) forms complex with in Th2 both cytokine and represses the Th1 IFN-γ. We define Gata3/Chd4/p300 transcriptional activation at loci Gata3/Chd4–nucleosome remodeling histone deacetylase...
SPI1 (also known as PU.1) is a dominant but transient regulator in early T-cell precursors and potent transcriptional controller of developmentally important pro-T-cell genes. Before T-lineage commitment, open chromatin frequently occupied by PU.1, many PU.1 sites lose accessibility when later down-regulated. Pioneering activity was tested this dynamic context quantitating the relationships between occupancy site quality levels naturally declined development using stage-specific gain-...
The zinc finger transcription factor, Bcl11b, is expressed in T cells and group 2 innate lymphoid (ILC2s) among hematopoietic cells. In early T-lineage cells, Bcl11b directly binds represses the gene encoding E protein antagonist, Id2, preventing pro-T from adopting innate-like fates. contrast, ILC2s co-express both Id2. To address this contradiction, we have compared action mechanisms ILC2s. We found that binding to regions across genome shows distinct cell type–specific motif preferences....