A5043028692- RNA Research and Splicing
- RNA modifications and cancer
- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Glycosylation and Glycoproteins Research
- MicroRNA in disease regulation
- Protein Kinase Regulation and GTPase Signaling
- Cellular transport and secretion
- Radioactive element chemistry and processing
- Cancer, Stress, Anesthesia, and Immune Response
- RNA Interference and Gene Delivery
- Immunotherapy and Immune Responses
- RNA and protein synthesis mechanisms
- Chromosomal and Genetic Variations
- Sphingolipid Metabolism and Signaling
- Cancer-related molecular mechanisms research
- Nuclear materials and radiation effects
- Calcium signaling and nucleotide metabolism
- Ion Transport and Channel Regulation
- Microbial metabolism and enzyme function
- TGF-β signaling in diseases
- RNA regulation and disease
- Neuropeptides and Animal Physiology
- Ferroptosis and cancer prognosis
- Aquatic life and conservation
Takeda (Japan)
2017-2024
International University of Health and Welfare
2023
Shizuoka Cancer Center
2012-2014
Tokyo Institute of Technology
1996-2012
Kindai University
2012
Japan Science and Technology Agency
2004
National Institute of Genetics
2004
Tokyo Metropolitan Institute of Medical Science
2003
Tokai University
2002
Mie University
1995-2000
Signal transducer and activator of transcription (STAT) 3, a member family DNA-binding molecules, is potential target in the treatment cancer. The highly phosphorylated STAT3 cancer cells contributes to numerous physiological oncogenic signaling pathways. Furthermore, significant association between glioblastoma multiforme stem-like cell (GBM-SC) development maintenance has been demonstrated recent studies. Previously, we reported novel small molecule inhibitor dimerization, STX-0119, as...
The characteristic structure of motor neurons (MNs), particularly the long axons, becomes damaged in early stages amyotrophic lateral sclerosis (ALS). However, molecular pathophysiology axonal degeneration remains to be fully elucidated.Two sets isogenic human-induced pluripotent stem cell (hiPSCs)-derived MNs possessing single amino acid difference (p.H517D) fused sarcoma (FUS) were constructed. By combining MN reporter lentivirus, specific phenotype was analyzed. Moreover, RNA profiling...
Cell type-specific transcriptomes are enabled by the action of multiple regulators, which frequently expressed within restricted tissue regions. In present study, we identify one such regulator, Quaking 5 (Qki5), as an RNA-binding protein (RNABP) that is in early embryonic neural stem cells and subsequently down-regulated during neurogenesis. mRNA sequencing analysis cell culture indicates Qki proteins play supporting roles transcriptome various forms processing may result from regionally...
Enhanced proliferation of airway smooth muscle is thought to contribute the pathogenesis asthma and other obstructive diseases. Lysophosphatidic acid (LPA) a simple bioactive lipid mediator that stimulates mitogenesis in fibroblasts some cell types. The effects LPA on cultured human cells were determined by measuring [3H]thymidine incorporation into cellular DNA. induced concentration-dependent stimulation similar magnitude serum, with 50 microM being those 5% serum. Stimulation serum was...
Phospholipase D (PLD) is involved in various aspects of cellular function. Two isoforms, PLD1 and PLD2, have been identified. PLD1, which has two splicing variants, regulated by factors, including ADP‐ribosylation factor (ARF). We here show that both variants are predominantly localized to late endosomes lysosomes, but not the Golgi apparatus or endoplasmic reticulum contrast earlier studies. Furthermore, PLD1s significant colocalization with an ARF6 mutant defective GTP binding. The data...
Pretreatment of cultured human tracheal smooth muscle cells with transforming growth factor-beta 1 (TGF-beta 1) decreased adenosine 3',5'-cyclic monophosphate (cAMP) accumulation by intact stimulated the beta-adrenergic agonist isoproterenol. The maximal inhibition isoproterenol-stimulated cAMP TGF-beta was 31 +/- 3%, and mean effective concentration (EC50) approximately 1.5 pM. response to isoproterenol but did not change EC50 value forskolin. pretreatment adenylyl cyclase activity measured...
Microprocessor complex, including DiGeorge syndrome critical region gene 8 (DGCR8) and DROSHA, recognizes cleaves primary transcripts of microRNAs (pri-miRNAs) in the maturation canonical miRNAs. The study DGCR8 haploinsufficiency reveals that efficiency this activity varies for different miRNA species. It is thought variation might be associated with risk schizophrenia 22q11 deletion caused by disruption gene. However, underlying mechanism varying action each remains largely unknown. Here,...
Stimulation of the epidermal growth factor receptor (EGFR) produces membrane ruffles through small G protein Rac1; however, signaling pathway from EGFR to Rac1 has not yet been clarified. Here, we show that autophosphorylation at tyrosine 992 is required for EGF‐induced ruffle formation in CHO cells. Signaling autophosphorylated appears be mediated by phospholipase C (PLC) γ1. Furthermore, activation EGF inhibited a PLC inhibitor. These results, taken together, suggest and subsequent PLCγ1...
Hepatocellular carcinoma (HCC) is still one of the major causes cancer-related death. Kinetochore-associated protein 2 (KNTC2) specifically upregulated in tumor tissues HCC patients and recognized as a potential candidate target for treatment HCC. However, relationship between KNTC2 vivo growth not yet fully understood. Here we encapsulated siRNAs into lipid nanoparticle (LNP) investigated their knockdown activity, engagement marker, anti-tumor activity hepatotoxicity an orthotopic model...
The DEAD-box family of RNA helicases plays essential roles in both transcriptional and translational mRNA degradation; they unwind short double-stranded by breaking the RNA-RNA interactions. Two helicases, eukaryotic translation initiation factor 4A3 (eIF4A3) helicase 3 (DDX3X), show high homology ATP-binding region are considered key molecules for cancer progression. Several small that target eIF4A3 DDX3X have been reported to inhibit cell growth; however, more potent compounds required...
The effects of the simple bioactive lipid mediator lysophosphatidic acid (LPA) on cAMP accumulation were investigated in cultured human airway smooth muscle cells (ASMC). Pretreatment with LPA induced an increase subsequent stimulation by forskolin and isoproterenol. When included during assay rather than as a pretreatment, inhibited but enhanced isoproterenol stimulation. Both completely blocked pertussis toxin treatment, whereas appeared relatively insensitive to toxin. protein kinase C...
Fused in sarcoma/translated liposarcoma (FUS) is a causative gene of amyotrophic lateral sclerosis (ALS). Mutated FUS causes accumulation DNA damage and cytosolic stress granule (SG) formation, thereby motor neuron (MN) death. However, key molecular aetiology remains unclear. Here, we applied novel platform technology, iBRN, "Non- biased" Bayesian regulatory network analysis based on induced pluripotent stem cell (iPSC)-derived model, to elucidate the using transcriptome iPSC-derived MNs...
1. Cultured bovine bronchial epithelial cells express a large number of β-adrenoceptors the β2 subtype which are coupled to activation adenylate cyclase and synthesis cyclic AMP. The mechanisms involved in agonist-induced desensitization β-adrenoceptor function these were investigated. 2. Preincubation with agonist isoprenaline induced rapid activity stimulated by (40% at 30 min) little or no decrease forskolin stimulation detected radioligand binding, indicating that uncoupling from had...
Of all potential biological therapeutics, monoclonal antibody (mAb)-based therapies are becomingthe dominant focus of clinical research. In particular, smaller recombinant fragments suchas single-chain variable (scFv) have become the subject intense focus. However, anefficient affinity ligand for fragment purification has not been developed. presentstudy, we designed a consensus sequence human heavy or light chain-variable regions(Fv) based on sequences available in ImMunoGeneTics...
Fused in sarcoma/translated liposarcoma (FUS) is an RNA-binding protein, and its mutations are associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), through the DNA damage stress response, aberrant granule (SG) formation, etc. We previously reported that translocation of endogenous FUS into SGs was achieved by cotreatment a double-strand break inducer inhibitor DNA-PK activity. In present study, we investigated cytoplasmic SG formation using various...