Hideaki Higashi

ORCID: 0000-0002-5370-7865
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About
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Research Areas
  • Helicobacter pylori-related gastroenterology studies
  • Cancer-related Molecular Pathways
  • Galectins and Cancer Biology
  • Bacillus and Francisella bacterial research
  • Bacteriophages and microbial interactions
  • Protein Tyrosine Phosphatases
  • Microtubule and mitosis dynamics
  • RNA modifications and cancer
  • Eosinophilic Esophagitis
  • Biochemical effects in animals
  • Antibiotic Resistance in Bacteria
  • Microbial Metabolites in Food Biotechnology
  • Epigenetics and DNA Methylation
  • Spine and Intervertebral Disc Pathology
  • NF-κB Signaling Pathways
  • Viral Infections and Vectors
  • Zoonotic diseases and public health
  • Microbial infections and disease research
  • Heart Rate Variability and Autonomic Control
  • Bacterial Genetics and Biotechnology
  • Identification and Quantification in Food
  • Rabies epidemiology and control
  • Veterinary medicine and infectious diseases
  • Viral gastroenteritis research and epidemiology
  • Genomics and Chromatin Dynamics

Hokkaido University
2016-2025

University of Zambia
2014-2021

National Institute of Infectious Diseases
2019

Jichi Medical University
2019

Medscape
2019

Tokyo University of Agriculture
2018

Yamaguchi University
2018

Institute of Infection and Immunity
2015

Molecular Oncology (United States)
2001-2008

The University of Tokyo
2005-2008

Helicobacter pylori CagA protein is associated with severe gastritis and gastric carcinoma. injected from the attached into host cells undergoes tyrosine phosphorylation. Wild-type but not phosphorylation-resistant induced a growth factor-like response in epithelial cells. Furthermore, formed physical complex SRC homology 2 domain (SH2)-containing phosphatase SHP-2 phosphorylation-dependent manner stimulated activity. Disruption of CagA-SHP-2 abolished CagA-dependent cellular response....

10.1126/science.1067147 article EN Science 2002-01-25

Helicobacter pylori is a causative agent of gastritis and peptic ulcer. cagA + H. strains are more virulent than − associated with gastric carcinoma. The gene product, CagA, injected by the bacterium into epithelial cells subsequently undergoes tyrosine phosphorylation. phosphorylated CagA specifically binds SHP-2 phosphatase, activates phosphatase activity, thereby induces morphological transformation cells. proteins most Western isolates have 34-amino acid sequence that variably repeats...

10.1073/pnas.222375399 article EN Proceedings of the National Academy of Sciences 2002-10-21

Infection with cagA-positive Helicobacter pylori is associated gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma of B cell origin. The cagA-encoded CagA protein delivered into epithelial cells via the bacterial type IV secretion system and, upon tyrosine phosphorylation by Src family kinases, specifically binds to aberrantly activates SHP-2 phosphatase, a bona fide oncoprotein in human malignancies. also elicits junctional polarity defects interacting inhibiting...

10.1073/pnas.0711183105 article EN Proceedings of the National Academy of Sciences 2008-01-12

<i>Helicobacter pylori</i> (<i>H. pylori</i>) is a causative agent of gastric diseases ranging from gastritis to cancer. The CagA protein the product the<i>cagA</i> gene carried among virulent <i>H. pylori</i>strains and associated with severe disease outcomes, most notably carcinoma. injected attached into epithelial cells undergoes tyrosine phosphorylation. phosphorylated binds activates SHP-2 phosphatase thereby induces growth factor-like morphological change termed "hummingbird...

10.1074/jbc.m208155200 article EN cc-by Journal of Biological Chemistry 2003-02-01

The CagA protein of <i>Helicobacter pylori</i>, which is injected from the bacteria into bacteria-attached gastric epithelial cells, associated with carcinoma. tyrosine-phosphorylated by Src family kinases, binds SH2 domain-containing SHP-2 phosphatase in a tyrosine phosphorylation-dependent manner, and deregulates its enzymatic activity. We established AGS human cells that inducibly express wild-type or phosphorylation-resistant CagA, residues constituting EPIYA motifs were substituted...

10.1074/jbc.m309964200 article EN cc-by Journal of Biological Chemistry 2004-04-01

Infection with cagA-positive Helicobacter pylori (H. pylori) is associated atrophic gastritis, peptic ulcer, and gastric adenocarcinoma. The cagA gene product CagA translocated from H. into epithelial cells undergoes tyrosine phosphorylation by Src family kinases (SFKs). Tyrosine-phosphorylated binds activates SHP-2 phosphatase the C-terminal kinase (Csk) while inducing an elongated cell shape termed “hummingbird phenotype.” Here we show that reduces level of focal adhesion (FAK) in cells....

10.1128/mcb.26.1.261-276.2006 article EN Molecular and Cellular Biology 2005-12-14

Activation of the transcription factor nuclear kappa B (NF-κB) is controlled by proteolysis its inhibitory subunit (IκB) via ubiquitin-proteasome pathway. Signal-induced phosphorylation IκBα a large multisubunit complex containing IκB kinases prerequisite for ubiquitination. Here, we show that FWD1 (a mouse homologue Slimb/βTrCP), member F-box/WD40-repeat proteins, associated specifically with only when phosphorylated. The introduction into cells significantly promotes ubiquitination and...

10.1073/pnas.96.7.3859 article EN Proceedings of the National Academy of Sciences 1999-03-30

We investigated the relationship between diversity of Helicobacter pylori CagA protein and clinical outcome. The cagA gene was sequenced in 115 isolates. binding affinity to Src homology 2 domain-containing tyrosine phosphatase (SHP-2) examined by vitro infection. Two major subtypes were observed--the East Asian Western type. grades inflammation, activity gastritis, atrophy significantly higher patients with gastritis infected CagA-positive strain than cagA-negative or strains. All strains...

10.1086/381782 article EN The Journal of Infectious Diseases 2004-02-23

Increased antimicrobial resistance (AMR) among bacteria underscores the need to strengthen AMR surveillance and promote data-based prescribing. To evaluate trends associations between usage (AMU) AMR, we explored a dataset of 34,672 bacterial isolates collected 2015 2020 from clinical samples at University Teaching Hospital (UTH) in Lusaka, Zambia. The most frequently isolated species were Escherichia coli (4,986/34,672; 14.4%), Staphylococcus aureus (3,941/34,672; 11.4%), Klebsiella...

10.1371/journal.pone.0302053 article EN cc-by PLoS ONE 2024-04-16

Chronic infection with cagA -positive Helicobacter pylori is associated the development of atrophic gastritis, peptic ulcers, and gastric adenocarcinoma. The gene product CagA injected into epithelial cells, where it undergoes tyrosine phosphorylation by Src family kinases. Translocated disturbs cellular functions physically interacting deregulating intracellular signaling transducers through both phosphorylation-dependent -independent mechanisms. To gain further insights pathophysiological...

10.1073/pnas.0502529102 article EN Proceedings of the National Academy of Sciences 2005-06-24

Helicobacter pylori contributes to the development of peptic ulcers and atrophic gastritis. Furthermore, H. strains carrying cagA gene are more virulent than cagA-negative associated with gastric adenocarcinoma. The product, CagA, is translocated into epithelial cells localizes inner surface plasma membrane, in which it undergoes tyrosine phosphorylation at Glu-Pro-Ile-Tyr-Ala (EPIYA) motif. Tyrosine-phosphorylated CagA specifically binds activates Src homology 2-containing protein-tyrosine...

10.1074/jbc.m503583200 article EN cc-by Journal of Biological Chemistry 2005-04-15

Helicobacter pylori cagA-positive strains are associated with gastric adenocarcinoma. The cagA gene product CagA is delivered into epithelial cells where it localizes to the plasma membrane and undergoes tyrosine phosphorylation at EPIYA-repeat region, which contains EPIYA-A segment, EPIYA-B Western CagA-specific EPIYA-C or East Asian EPIYA-D segment. In host cells, specifically binds deregulates SHP-2 phosphatase via tyrosine-phosphorylated thereby inducing an elongated cell shape known as...

10.1074/jbc.m606172200 article EN cc-by Journal of Biological Chemistry 2006-09-06

ABSTRACT Colonization of the stomach mucosa by Helicobacter pylori is a major cause acute and chronic gastric pathologies in humans. Several H. virulence genes that may play role its pathogenicity have been identified. The most important determinants are vacA cagA cag island ( PAI) genes. In present study, to consider association molecular genetics between PAI regarding clinical outcome, we selected strains with various genotypes Japan sequenced full-length , cagE Sequencing revealed...

10.1128/jcm.43.8.3906-3916.2005 article EN Journal of Clinical Microbiology 2005-08-01

The epidemiology of extended-spectrum β-lactamases (ESBLs) has undergone dramatic changes, with CTX-M-type enzymes prevailing over other types. blaCTX-M genes, encoding ESBLs, are usually found on plasmids, but chromosomal location is becoming common. Given that blaCTX-M-harboring strains often exhibit multidrug resistance (MDR), it important to investigate the association between chromosomally integrated and presence additional antimicrobial (AMR) identify relevant genetic elements.A total...

10.1186/s13756-021-00941-8 article EN cc-by Antimicrobial Resistance and Infection Control 2021-05-10

Since research on Leptospira has focused pathogenic leptospires, which are supposed to multiply only in animal hosts, the life cycle of saprophytic leptospires long been a mystery. This study demonstrates that both and waterlogged soil, mimics postflooding environment.

10.1128/spectrum.02157-21 article EN Microbiology Spectrum 2022-03-15
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