- Genomics, phytochemicals, and oxidative stress
- Epigenetics and DNA Methylation
- Hemoglobinopathies and Related Disorders
- Glutathione Transferases and Polymorphisms
- Synthesis and Biological Evaluation
- RNA modifications and cancer
- Lung Cancer Treatments and Mutations
- Acute Myeloid Leukemia Research
- Erythrocyte Function and Pathophysiology
- Genomics and Chromatin Dynamics
- Kruppel-like factors research
- Advanced Biosensing Techniques and Applications
- RNA and protein synthesis mechanisms
- Spaceflight effects on biology
- Cancer Genomics and Diagnostics
- Trauma Management and Diagnosis
- Birth, Development, and Health
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- HER2/EGFR in Cancer Research
- Platelet Disorders and Treatments
- Pleural and Pulmonary Diseases
- Genetics and Neurodevelopmental Disorders
- Boron Compounds in Chemistry
Tohoku University
2015-2024
Juntendo University Shizuoka Hospital
2023-2024
Kumamoto University
2021-2023
Juntendo University
1985-2020
Toyota Motor Corporation (Switzerland)
2020
Japan Radioisotope Association
2017-2020
Tochigi Cancer Center
2018
Miyagi Prefectural Hospital Organization
2018
Kumamoto University Hospital
2018
Chiba University
2015
The identity and behavior of mouse spermatogenic stem cells have been a long-standing focus interest. In the prevailing "As model," cell function is restricted to singly isolated (As) spermatogonia. By examining single-cell dynamics GFRα1+ in vivo, we evaluate an alternative hypothesis that, through fragmentation, syncytial spermatogonia also contribute homeostasis. We use live imaging pulse labeling quantitatively determine fates individual find during steady-state spermatogenesis, entire...
Significance Sickle cell disease (SCD) is one of the most common inherited disorders. A mutation in β-globin gene causes deformation red blood cells into a sickle shape, which turn intravascular hemolysis and vaso-occlusion resulting damage to multiple organs. Most studies that propose develop new SCD therapies include induction fetal γ-globin expression inhibit formation as their ultimate goal. In contrast, we demonstrate here activation nuclear factor erythroid 2-related 2 (Nrf2)...
A case of congenital goiter with defective thyroglobulin synthesis has been studied in molecular terms. The patient is the fifth a kindred six, three which have goiter. parents are first cousins. Segregation alleles family was by Southern blotting probe revealing diallelic restriction fragment length polymorphism (RFLP). results demonstrated that affected siblings were homozygous for RFLP. Northern analysis RNA suggested mRNA size slightly reduced. Polymerase chain reaction amplification...
Xylene monooxygenase, encoded by the TOL plasmid of Pseudomonas putida, catalyzes oxidation toluene and xylenes consists two different subunits xylA xylM. In this study, complete nucleotide sequences these genes were determined amino acid xylM products deduced. The XylM sequence had a 25% homology with alkane hydroxylase, which omega-hydroxylation fatty acids terminal hydroxylation alkanes. first 90 XylA exhibited strong similarity to chloroplast-type ferredoxins, whereas rest resembled that...
Transcription factor GATA 2 is highly expressed in hematopoietic stem cells and progenitors, whereas its expression declines after erythroid commitment of progenitors. In contrast, the start 1 coincides with increases along differentiation. We refer this dynamic transition to as ‘ switching’. Here, we examined contribution switching Gata1‐ knockdown embryos that concomitantly express Gata2 ‐ GFP reporter, high‐level reporter was detected accumulated immature impaired differentiation,...
The transcription factor Nrf2 activates of cytoprotective genes during oxidative and electrophilic insults. activity is regulated by Keap1 in a stress-dependent manner normal cells, somatic loss-of-function mutations are known to induce constitutive activation, especially lung adenocarcinomas, conferring survival proliferative benefits tumors. Therefore, several therapeutic strategies that aim inhibit tumors have been developed for the treatment Nrf2-activated cancers. Here we addressed...
Abstract Space flight produces an extreme environment with unique stressors, but little is known about how our body responds to these stresses. While there are many intractable limitations for in-flight space research, some can be overcome by utilizing gene knockout-disease model mice. Here, we report deletion of Nrf2, a master regulator stress defense pathways, affects the health mice transported stay in International Station (ISS). After 31 days ISS, all returned safely Earth....
Abstract Aberrant activation of NRF2 is as a critical prognostic factor that drives the malignant progression various cancers. Cancer cells with persistent heavily rely on activity for therapeutic resistance and aggressive tumorigenic capacity. To clarify metabolic features NRF2‐activated lung cancers, we conducted targeted metabolomic (T‐Met) global (G‐Met) analyses non–small‐cell cancer (NSCLC) cell lines in combination exome transcriptome analyses. Exome analysis 88 (49 adenocarcinoma, 14...
Nrf2 activates cytoprotective gene expression, and activity is regulated through at least two protein degradation pathways: the Keap1-mediated β-TrCP-mediated pathways. To address relative contributions of these pathways, we generated knock-in mouse lines expressing an Nrf2SA mutant that harbored substitution mutations serine residues interacting with β-TrCP. The homozygous (Nrf2SA/SA) mice grew normally, levels comparable to those wild-type (WT) under unstressed conditions. However, when...
Abstract Purpose: We assessed the intratumor pharmacokinetics of [fam-] trastuzumab deruxtecan, T-DXd (known as DS-8201a), a novel HER2-targeted antibody–drug conjugate, using phosphor-integrated dots (PID)-imaging analysis to elucidate its pharmacologic mechanism. Experimental Design: used two mouse xenograft models administered at concentration 4 mg/kg: (i) heterogeneous model in which HER2-positive and HER2-negative cell lines were mixed, (ii) homogeneous both types transplanted...
Spaceflight-related stresses impact health via various body systems, including the haematopoietic and immune with effects ranging from moderate alterations of homoeostasis to serious illness. Oxidative stress appears be involved in these changes, transcription factor Nrf2, which regulates expression a set cytoprotective antioxidative response genes, has been implicated spaceflight-induced stresses. Here, we show through analyses mice MHU-3 project, Nrf2-knockout travelled space for 31 days,...
AbstractGATA1 is a key regulator of erythroid cell differentiation. To examine how Gata1 gene expression regulated in stage-specific manner, transgenic mouse lines expressing green fluorescent protein (GFP) reporter from the locus bacterial artificial chromosome (G1BAC-GFP) were prepared. We found that GFP faithfully recapitulated expression. Using fluorescence combination with hematopoietic surface markers, we established purification protocol for two progenitor fractions, referred to as...
The KEAP1-NRF2 pathway is the principal protective response to oxidative and electrophilic stresses. Under homeostatic conditions, KEAP1 forms part of an E3 ubiquitin ligase, which tightly regulates activity transcription factor NRF2 by ...