- RNA Research and Splicing
- Cancer Cells and Metastasis
- Estrogen and related hormone effects
- Congenital heart defects research
- Renal and related cancers
- Genomics and Chromatin Dynamics
- Developmental Biology and Gene Regulation
- Wnt/β-catenin signaling in development and cancer
- Coronary Artery Anomalies
- HER2/EGFR in Cancer Research
- 14-3-3 protein interactions
- RNA and protein synthesis mechanisms
- Cancer-related gene regulation
- Cell Adhesion Molecules Research
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Congenital Heart Disease Studies
- DNA Repair Mechanisms
- Neonatal Respiratory Health Research
- Cellular Mechanics and Interactions
- Bacterial Genetics and Biotechnology
- Cancer therapeutics and mechanisms
- Hippo pathway signaling and YAP/TAZ
- Cancer Research and Treatments
- Immunotherapy and Immune Responses
Kyoto University Hospital
2022
Foundation for Biomedical Research and Innovation
2019-2021
Kyoto University
2007-2021
Foundation for Biomedical Research
2021
Institute for Biomedical Research and Innovation
2021
University of Minnesota
2010-2020
Institut thématique Génétique, génomique et bioinformatique
2012
Stem Cell Institute
2012
Kindai University
2007-2009
National Institute of Advanced Industrial Science and Technology
2007
Adult zebrafish possess a significant ability to regenerate injured heart tissue through proliferation of pre-existing cardiomyocytes, which contrasts with the inability mammals do so after immediate postnatal period. Zebrafish therefore provide model system in study how an can be repaired. However, it remains unknown what important processes cardiomyocytes are involved other than partial de-differentiation and proliferation. Here we show that migration injury site is essential for...
Significance BRCA1 plays a key role in homology-directed repair (HDR) S/G 2 -phase cells. It remains unclear why mutation carriers develop cancer predominantly breast and ovarian tissues. We revealed that physiological concentration (10 nM) of estrogens efficiently induce TOP2β-dependent DSBs the absence cells arrested G 1 phase. This genotoxicity was confirmed also 0 /G epithelial mouse mammary glands. These findings indicated contributes to DSB independent HDR. Our data suggested promotes...
Two-component signal-transduction systems (TCSs) of bacteria are considered to form an intricate signal network cope with various environmental stresses. One example such a in Escherichia coli is the transduction cascade from EvgS/EvgA system PhoQ/PhoP system, where activation promotes expression PhoP-activated genes. As factor connecting this cascade, we have identified small inner membrane protein (65 aa), B1500. Expression b1500 gene directly regulated by and heterologous promoter...
How divergent genetic systems regulate a common pathway during the development of two serial structures, forelimbs and hindlimbs, is not well understood. Specifically, HAND2 has been shown to Shh directly initiate its expression in posterior margin limb mesenchyme. Although Hand2-Shh morphoregulatory system operates both forelimb hindlimb bud, recent analysis suggested that upstream regulation different bud. A combination all four Hox9 genes required for Hand2 forelimb-forming region;...
The zebrafish is a widely used model animal to study the regeneration of organs, such as fin and heart. Their average lifetime about 3 years, recent studies have shown that exhibit aging-related degeneration, suggesting possibility aging might affect regenerative potential. In order investigate this possibility, we compared heart after experimental amputation in young (6-12 month old) old (26-36 fish. Comparison recovery rate caudal fin, measured every two or three days from one day post...
Using an EvgS-active mutant (evgS1) in combination with gene deletions, we clarified the molecular mechanism of transcriptional cascade acid resistance and multidrug genes initiated by EvgS/EvgA two-component system Escherichia coli, followed sequential induction regulators, YdeO GadE. Overexpression EvgA, response regulator system, is known to induce expression a number genes, which EvgA-YdeO-GadE circuit involved, but role sensor EvgS this has remained unsolved. Our results suggest that...
The transcriptional basis of vertebrate limb initiation, which is a well-studied system for the initiation organogenesis, remains elusive. Specifically, involvement β-catenin pathway in as well its role hindlimb-specific regulation, are under debate. Here, we show that active limb-forming area mouse embryos. Furthermore, conditional inactivation Islet1, factor, lateral plate mesoderm results failure to induce hindlimb outgrowth. We further Islet1 required nuclear accumulation and hence...
Abstract Nuclear expression of Y-box–binding protein (YBX1) is closely correlated with clinical poor outcomes and drug resistance in breast cancer. translocation YBX1 facilitated by phosphorylation at serine 102 AKT, p70S6K, p90RSK, the phosphorylated (pYBX1) promotes genes related to cell growth. A forthcoming problem be addressed whether targeting overcomes antiestrogen progressive Here, we found that increased pYBX1 was accompanied acquired antiestrogens, fulvestrant tamoxifen. Forced...
Abstract Understanding the mechanism by which cancer cells enhance stemness facilitates therapies. Here, we revealed that a stem cell transcription factor, SALL 4, functions to in basal‐like breast cells. We used sh RNA ‐mediated knockdown and gene overexpression systems analyze functions. To evaluate stemness, performed sphere formation assay. In 4 cells, ability was reduced, indicating enhances stemness. CD 44 is membrane protein known as factor cancer. splicing variants are involved...
Gamma-aminobutyric acid (GABA) is a non-protein amino and contained in various foods, such as fruits vegetables. Although health benefits of GABA have been reported, seems to unidentified functions. In this study, we first show increase intracellular level GABA-treated breast cancer cell lines, MCF-7 T-47D, analyses immunofluorescence. our experimental condition, treatment reduced estradiol-stimulated growth these lines. addition, performed mouse early induction model system investigate...
In cell cultures, the dispersed phenotype is indicative of migratory ability. Here we characterized Sal‐like 4 ( SALL4 ) as a dispersion factor in basal‐like breast cancer. Our shRNA‐mediated knockdown system and overexpression revealed that suppresses expression adhesion gene CDH1 , positively regulates suppressor ZEB1 . Cell behavior analyses showed intercellular maintains motility after cell–cell interaction division, which results phenotype. findings indicate functions to suppress maintain
The chromatin factors Hmgb1 and Hmgb2 have critical roles in cellular processes, including transcription DNA modification. To identify the function of Hmgb genes embryonic development, we generated double mutants Hmgb1;Hmgb2 mice. While null embryos arrest at E9.5, Hmgb1(-/-) ; Hmgb2(+/-) exhibit a loss digit5, most posterior digit, forelimb. We show that forelimbs reduced level Shh signaling, as well clear downregulation Wnt BMP target region. Moreover, demonstrate hmgb1 hmgb2 zebrafish...
The enhanced expression of the Y-box binding protein YBX1 is consistently correlated with poor outcomes or reduced survival breast cancer patients. However, mechanism underlying association between increased and has yet to be revealed. We searched a database for top 500 genes that are positively negatively ESR1 in further examined YBX1-correlated patients at Kyushu University Hospital. More than 60% also ESR1. levels 20 mostly predict negative outcomes, while positive outcomes. Furthermore,...
Sal-like 4 (SALL4) is a transcription factor that enhances proliferation and migration in breast cancer cells. SALL4 expression therefore has the potential to promote malignancy. However, regulatory mechanisms involved protein have not been thoroughly elucidated. In this study, we observed treating MCF-7 SUM159 cell lines with proteasome inhibitor increases levels, suggesting degraded by ubiquitin-proteasome system. Using immunoprecipitation uncover SALL4-binding proteins, identified an E3...
Background: The zebrafish heart regenerates after various severe injuries. Common processes of regeneration are cardiomyocyte proliferation, activation epicardial tissue, and neovascularization. In order to further characterize processes, we introduced milder injuries compared responses those induced by ventricular apex resection, a widely used injury method. We scratching the surface puncturing ventricle with fine tungsten needle as injury‐inducing techniques. Results: Scratching subtle...
ATM gene mutation carriers are predisposed to estrogen-receptor-positive breast cancer (BC). prevents BC oncogenesis by activating p53 in every cell; however, much remains unknown about tissue-specific after loss. Here, we report that controls the early transcriptional response estrogens. This depends on topoisomerase II (TOP2), which generates TOP2-DNA double-strand break (DSB) complexes and rejoins breaks. When TOP2-mediated ligation fails, facilitates DSB repair. After estrogen exposure,...
Mammary ductal dysplasia is a phenotype observed in precancerous lesions and early-stage breast cancer. However, the mechanism of formation remains elusive. Here we show, by establishing novel model system, that estrogen, female hormone, has potential to cause mammary dysplasia. We injected estradiol (E2), most active form daily into scid mice with defect non-homologous end joining repair cell proliferation at day 30. The protooncogene Myc downstream target estrogen signaling, found its...
Abstract Background Pmp22 , a member of the junction protein family Claudin/EMP/PMP22, plays an important role in myelin formation. Increase pmp22 transcription causes peripheral neuropathy, Charcot-Marie-Tooth disease type1A (CMT1A). The pathophysiological phenotype CMT1A is aberrant axonal myelination which induces reduction nerve conduction velocity (NCV). Several model rodents have been established by overexpressing . Thus, it thought that expression must be tightly regulated for correct...
Medaka is a small Asian freshwater teleost and has been an excellent model for fertilization studies more than 50 years. Therefore, experimental procedures in vitro (IVF) cryopreservation of sperm are well established. In contrast, since the eggs or early embryos can not be cryopreserved, many females killed to obtain unfertilized IVF. Recent progress genomics establishing medaka as new animal functional genomics, numerous mutant transgenic strains have established stored frozen sperm....
Abstract Background The regeneration of larvae zebrafish fin emerged as a new model in the last decade. In contrast to genetic tools study regeneration, chemical probes modulate and interrogate processes are not well developed. Results We set up assay system tested activities natural product compounds extracts, prepared from various microbes. Colomitide C, recently isolated fungus obtained Antarctica, inhibited regeneration. Using fluorescent reporter transgenic lines, we show that...
Abstract A drug for metastasis prevention is necessary. The orally administered anticancer S‐1 contributes to cancer therapy. In a mouse xenograft model of metastatic breast from our previous study, the administration inhibited lung metastasis. However, mechanism inhibition remains elusive. contains 5‐chloro‐2,4‐dihydroxypyridine ( CDHP ), which does not have antigrowth activity, but prevents degradation 5‐fluorouracil, an reagent. this we found that treatment shrinks cell morphology in...