A5055427979- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Amino Acid Enzymes and Metabolism
- Biochemical and Molecular Research
- Cellular transport and secretion
- Protein Kinase Regulation and GTPase Signaling
- Protein Tyrosine Phosphatases
- RNA modifications and cancer
- Hippo pathway signaling and YAP/TAZ
- Cancer-related gene regulation
- ATP Synthase and ATPases Research
- Metabolism and Genetic Disorders
- Calcium signaling and nucleotide metabolism
- HIV/AIDS drug development and treatment
- PI3K/AKT/mTOR signaling in cancer
- Cytomegalovirus and herpesvirus research
- CRISPR and Genetic Engineering
- Autophagy in Disease and Therapy
- Phagocytosis and Immune Regulation
- Signaling Pathways in Disease
- Neurogenesis and neuroplasticity mechanisms
- Pancreatic function and diabetes
- Tissue Engineering and Regenerative Medicine
- Thyroid Cancer Diagnosis and Treatment
- Adenosine and Purinergic Signaling
Tokyo Medical and Dental University
2020-2024
University of Cincinnati Medical Center
2015-2024
The University of Tokyo
2006-2023
Hiroshima University
2017-2019
University of Cincinnati
2016-2019
Oncology Hematology Care
2017
Cancer Institute (WIA)
2016
Akita University
2009-2015
Center for Global Health
2013
Oncogenic mutations drive anabolic metabolism, creating a dependency on nutrient influx through transporters, receptors, and macropinocytosis. While sphingolipids suppress tumor growth by downregulating macropinocytosis autophagy still provide cancer cells with fuel. Therapeutics that simultaneously disrupt these parallel access pathways have potential as powerful starvation agents. Here, we describe water-soluble, orally bioavailable synthetic sphingolipid, SH-BC-893, triggers transporter...
Abstract Inositol polyphosphate 4-phosphatase B (INPP4B) has been identified as a tumor suppressor mutated in human breast, ovary, and prostate cancers. The molecular mechanism underlying INPP4B's tumor-suppressive role is currently unknown. Here, we demonstrate that INPP4B restrains development by dephosphorylating the PtdIns(3,4,5)P3 accumulates situations of PTEN deficiency. In vitro, directly dephosphorylates PtdIns(3,4,5)P3. vivo, neither inactivation Inpp4b (Inpp4bΔ/Δ) nor heterozygous...
Previous studies showed that five miRNAs (miR-885-5p, miR-1274, miR-210-3p, miR-224 and miR-1290) were upregulated the most in clear cell renal carcinoma (ccRCC). Our focus was to understand from a clinical standpoint functional consequences of upregulating miR-210-3p. Towards this, we utilized CRISPR/Cas9 gene editing system deplete miR-210-3p RCC lines (786-o, A498 Caki2) characterized outcomes. We observed depletion dramatically increased tumorigenesis, including altering morphology Caki2...
Abstract Continuous activation of hypoxia-inducible factor (HIF) is important for progression renal cell carcinoma (RCC) and acquired resistance to antiangiogenic multikinase mTOR inhibitors. Recently, HIF2α antagonists PT2385 PT2399 were developed are being evaluated in a phase I clinical trial advanced or metastatic clear RCC (ccRCC). However, would be expected develop. In this study, we identified signals activated by deficiency as candidate mediators the antagonists. We established...
The metabolism of membrane phosphoinositides is critical for a variety cellular processes. Phosphatidylinositol-3,5-bisphosphate [PtdIns(3,5)P 2 ] controls multiple steps the intracellular trafficking system in both yeast and mammalian cells. However, other than neuronal tissues, little known about physiological functions PtdIns(3,5)P mammals. Here, we provide genetic evidence that type III phosphatidylinositol phosphate kinase (PIPKIII), which produces , essential polarized epithelial...
Autophagy is a dynamic process that degrades subcellular constituents, and its activity measured by autophagic flux. The tandem proteins RFP-GFP-LC3 GFP-LC3-RFP-LC3ΔG, which enable the visualization of vacuoles different stages differences in their fluorescent color, are useful tools to monitor flux, but they require plasmid transfection. In this study, we hence aimed develop new method flux using small cell-permeable probes. We previously developed two green-fluorescent probes, DALGreen...
// Laura R. H. Ip 1 , George Poulogiannis 2 Felipe Cia Viciano 1, 3 Junko Sasaki 4 Satoshi Kofuji Victoria J. Spanswick 5 Daniel Hochhauser John A. Hartley Takehiko Christina Gewinner Department of Cancer Biology, UCL Institute, University College London, UK The Institute Research, Signalling and Metabolism, Faculty Infectious Tropical Diseases, Immunology Infection Department, London School Hygiene & Medical Akita Medicine, Akita, Japan Research Drug-DNA Interaction Group, Correspondence...
Genetic S6K1 inactivation can induce apoptosis in PTEN-deficient cells. We analyzed the therapeutic potential of inhibitors T cell leukemia and glioblastoma. Results revealed that inhibitor LY-2779964 was relatively ineffective as a single agent, while S6K1-targeting AD80 induced cytotoxicity selectively In vivo, rescued 50% mice transplanted with Cells surviving treatment exhibited inhibitor-induced phosphorylation due to increased mTOR-S6K1 co-association, which primed rapid recovery...
PIKfyve phosphorylates PtdIns(3)P to PtdIns(3, 5)P2. One of the best characterized effector downstream 5)P2 is a lysosomal Ca2+ channel, TRPML1. Although it has been reported that TRPML1 involved in phagosome-lysosome fusion, relevance channel phagosome acidification denied. In this article, however, we demonstrated was dependent on Based classical idea Fluorescein isothiocyanate (FITC)-fluorescence highly sensitive acidic pH, could estimate by time laps imaging. FITC-zymosan fluorescence...
TMEM55B is first identified as phosphatidylinositol-4,5-P24-phosphatases (PtdIns-4,5-P24-phosphatases) that catalyse dephosphorylation of PtdIns-4,5-P2 to PtdIns-5-P. We demonstrate for the time phosphorylated by Erk/MAPK and this mechanism participates in regulation lysosomal clustering. Exposure RAW264.7 macrophages various stimuli induces phosphorylation on Ser76 Ser169, sites corresponding consensus sequences (PX(S/T)P) MAPK. Of these stimuli, Toll-like receptor ligands most strongly...
The emerging concepts of fetal-like reprogramming following tissue injury have been well recognized as an important cue for resolving regenerative mechanisms intestinal epithelium during inflammation. We previously revealed that the remodeling mesenchyme with collagen fibril induces YAP/TAZ-dependent fate conversion intestinal/colonic epithelial cells covering wound bed towards progenitors. To fully elucidate underlying link between extracellular matrix (ECM) and cells, it is critical to...
Abstract Cell competition is a biological process by which unfit cells are eliminated from “cell society.” We previously showed that cultured mammalian epithelial Madin‐Darby canine kidney (MDCK) expressing constitutively active YAP were apical extrusion when surrounded “normal” MDCK cells. However, the molecular mechanism underlying elimination of YAP‐expressing was unknown. Here, we used high‐throughput chemical compound screening to identify cyclooxygenase‐2 (COX‐2) as key molecule...
ABSTRACT TMEM55a (also known as PIP4P2) is an enzyme that dephosphorylates the phosphatidylinositol (PtdIns) PtdIns(4,5)P2 to form PtdIns(5)P in vitro. However, vivo conversion of polyphosphoinositide into by phosphatase has not yet been demonstrated, and role remains poorly understood. Here, we found mouse macrophages (Raw264.7) deficient showed increased engulfment large particles without affecting phagocytosis Escherichia coli. Transfection a bacterial with similar substrate specificity...
The circadian clock is a highly conserved 24 h biological oscillation mechanism and affected by environmental stimuli such as light, food temperature. Disruption of the results in disorders diverse processes, including sleep-wake cycle metabolism. Although we previously identified several components zebrafish, our understanding relationship between light-inducible genes metabolism remains incomplete. To investigate how regulate metabolism, performed transcriptomic metabolomic analyses zPer2,...
RAS is the founding member of a superfamily GTPases and regulates signaling pathways involved in cellular growth control. While recent studies have shown that activation state can be controlled by lysine ubiquitylation acetylation, existence methylation remains unexplored. In contrast to does not alter side chain charge it has been challenging deduce its impact on protein structure conventional amino acid substitutions. Herein, we investigate RAS-related GTPases. We developed GoMADScan (Go...