Hiroyuki Toh

Computational Biology Research Center, Edo, Tōkyō, Japan

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Publications (149)821.08 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Dengue viruses (DEN) are classified into four serotypes (DEN1-DEN4) exhibiting high sequence and structural similarities, and infections by multiple serotypes can lead to the deadly dengue hemorrhagic fever. Here, we aim at characterizing the thermodynamic stability of DEN envelope protein domain III (ED3) during its evolution, and we report a structural analysis of DEN4wt ED3 combined with a systematic mutational analysis of residues 310 and 387. Molecular modeling based on our DEN3 and DEN4 ED3 structures indicated that the side-chains of residues 310/387, which are Val(310)/Ile(387) and Met(310)/Leu(387) in DEN3wt and DEN4wt, respectively, could be structurally compensated, and that a "size switch type repacking" might have occurred at these sites during the evolution of DEN into its four serotypes. This was experimentally confirmed by a 10ºC and 5ºC decrease in the thermal stability of, respectively, DEN3 ED3 variants with Met(310)/Ile(387) and Val(310)/Leu(387), whereas the variant with Met(310)/Leu(387), which contain a double mutation, had the same stability as the wild type DEN3. Namely, the Met310Val mutation should have preceded the Leu387Ile mutation in order to maintain the tight internal packing of ED3 and thus its thermodynamic stability. This view was confirmed by a phylogenetic reconstruction indicating that a common DEN ancestor would have Met(310)/Leu(387), and the intermediate node protein, Val(310)/Leu(387), which then mutated to the Val(310)/Ile(387) pair found in the present DEN3. The hypothesis was further confirmed by the observation that all of the present DEN viruses exhibit only stabilizing amino acid pairs at the 310/387 sites.
    Biochimica et Biophysica Acta 12/2013; · 4.66 Impact Factor
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    ABSTRACT: Circulating tumor cells (CTCs) in the blood have attracted attention as biomarkers and seeds of metastasis. However, systems that detect CTC on the basis of epithelial markers (e.g., EpCAM, cytokeratins) may miss many tumor cells as a result of marker downregulation after epithelial-mesenchymal transition (EMT). The purpose of this study was to define CTC-based prognostic markers in colorectal cancer that are not repressed by EMT. Here we report Plastin3 (PLS3) as a novel CTC marker associated with with invasive and metastatic capabilities of colorectal cancer cells. Employing a qRT-PCR assay specific for PLS3, peripheral blood samples of CRC patients were analyzed (training set, n = 381; validation set, n = 330). PLS3 was not expressed by normal blood cells. Its expression was high in metastatic CRC cells and it was not downregulated during EMT. Detection of PLS3-positive CTC in peripheral blood was associated with reduced overall patient survival. Multivariate analysis showed that this prognostic influence was independent from established risk factors. In particular, in Dukes grade B and C patients, detection of PLS3-positive CTC was determined to be the most significant prognostic factor, surpassing other currently available clinicopathological factors. Our results firmly establish PLS3 as a novel marker for the detection of metastatic CRC cells in the blood, offering a significant value compared to other known prognostic factors.
    Cancer Research 02/2013; · 9.28 Impact Factor
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    ABSTRACT: BACKGROUND: The oncogenic single nucleotide polymorphism rs6983267, located on 8q24.21, may affect copy number aberrations and/or expression profiles in colorectal cancer (CRC). We investigated the role of this single nucleotide polymorphism in the clinical outcome of CRC. METHODS: Array comparative genomic hybridization (aCGH) and oligomicroarrays were performed on cancer cells from 157 primary CRC tissues. Expression profiles were analyzed by means of extraction expression module (EEM) analyses. Mutations in TP53, KRAS, and BRAF and microsatellite instability were also examined in 107 of the 157 cases. RESULTS: aCGH analysis revealed two clusters; more frequent genomic copy number alteration (CNA) was observed in the 89 cases in cluster B than in the 18 cases in cluster A. The average CNA was higher in samples containing the major allele (GT/TT) of rs6983267 than in those containing the minor allele (GG). Additionally, MYC expression was the highest in samples containing the GG allele (n = 18), followed by the GT and TT alleles (n = 41 and 48, respectively). EEM analysis revealed dominant up-regulation of MYC in samples containing the minor allele. Moreover, the presence of the minor allele in a MYC-positive, CNA-negative context predicted a poorer prognosis than the presence of the major allele in a MYC-negative, CNA-positive context in CRC. CONCLUSIONS: The presence of the minor allele of rs6983267 at 8q24.21 worsened the prognosis of CRC through up-regulation of MYC transcription. Furthermore, progression of CRC may require global CNA in the presence of the major allele and with lack of MYC transcription.
    Annals of Surgical Oncology 09/2012; · 4.12 Impact Factor
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    ABSTRACT: FBXW7 is a tumor suppressor gene that plays a role in cell cycle regulation via Myc degradation. However, the clinical significance of FBXW7 in esophageal squamous cell carcinoma (ESCC) has not been evaluated. The purpose of this study was to assess the clinical significance of FBXW7 for prognosis in human ESCC. Real-time RT-PCR was used to examine the expression of FBXW7 to determine its clinicopathological significance in 75 cases of ESCC. Overall survival rate was calculated using the Kaplan-Meier method, while multivariate survival was analyzed with the Cox hazard model. FBXW7 suppression analysis was performed to examine proliferation potency and Myc expression in the FBXW7 siRNA groups. The relationship between FBXW7 expression and the copy number loss of FBXW7 was examined in clinical samples of ESCC. Finally, FBXW7 copy number loss was linked to prognosis in 42 ESCC patients. FBXW7 expression in cancer was lower compared to non-cancer tissues (P=0.003) and is an independent prognostic factor. The proliferation rates and Myc protein expression were significantly enhanced in FBXW7 siRNA cells compared to the controls. Cases with a loss of FBXW7 copy number had low FBXW7 expression and a poorer prognosis than cases with no loss of copy number. Genetic alterations in esophageal cancer lead to the loss of FBXW7 expression and increased cell proliferation. These genetic alterations of FBXW7 status may provide a prognostic factor for ESCC patients.
    International Journal of Oncology 07/2012; 41(1):253-9. · 2.66 Impact Factor
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    Wataru Nemoto, Hiroyuki Toh
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    ABSTRACT: BACKGROUND: The detection of conserved residue clusters on a protein structure is one of the effective strategies for the prediction of functional protein regions. Various methods, such as Evolutionary Trace, have been developed based on this strategy. In such approaches, the conserved residues are identified through comparisons of homologous amino acid sequences. Therefore, the selection of homologous sequences is a critical step. It is empirically known that a certain degree of sequence divergence in the set of homologous sequences is required for the identification of conserved residues. However, the development of a method to select homologous sequences appropriate for the identification of conserved residues has not been sufficiently addressed. An objective and general method to select appropriate homologous sequences is desired for the efficient prediction of functional regions. RESULTS: We have developed a novel index to select the sequences appropriate for the identification of conserved residues, and implemented the index within our method to predict the functional regions of a protein. The implementation of the index improved the performance of the functional region prediction. The index represents the degree of conserved residue clustering on the tertiary structure of the protein. For this purpose, the structure and sequence information were integrated within the index by the application of spatial statistics. Spatial statistics is a field of statistics in which not only the attributes but also the geometrical coordinates of the data are considered simultaneously. Higher degrees of clustering generate larger index scores. We adopted the set of homologous sequences with the highest indexscore, under the assumption that the best prediction accuracy is obtained when the degree of clustering is the maximum. The set of sequences selected by the index led to higher functional region prediction performance than the sets of sequences selected by other sequence-based methods. CONCLUSIONS: Appropriate homologous sequences are selected automatically and objectively by the index. Such sequence selection improved the performance of functional region prediction. As far as we know, this is the first approach in which spatial statistics have been applied t o protein analyses. Such integration of structure and sequence information would be useful for other bioinformatics problems.
    BMC Structural Biology 05/2012; 12(1):11. · 2.10 Impact Factor
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    ABSTRACT: Colorectal cancer (CRC) oncogenesis was considered to be determined by interactions between genetic and environmental factors. Specific interacting factors that influence CRC morbidity have yet to be fully investigated. A multi-institutional collaborative study with 1511 CRC patients and 2098 control subjects was used to compare the odds ratios for the occurrence of polymorphisms at 11 known single nucleotide polymorphisms (SNPs). TaqMan PCR and questionnaires were used to evaluate the effects of environmental exposures. Variants of rs6983267 on 8q24 were the most significant markers of risk for CRC (odds ratio 1.16, 95% confidence interval 1.06-1.27, P = 0.0015). Non-insulin-dependent diabetes mellitus (DM), a higher body mass index at age 20, and meat consumption were environmental risk factors, whereas a tuna-rich diet and vitamin intake were protective factors. The cohort of rs6983267 SNP major (T) allele at 8q24 and DM had a 1.66-fold higher risk ratio than the cohort of major allele patients without DM. We confirmed that interactions between the genetic background and environmental factors are associated with increased risk for CRC. There is a robust risk of the minor G allele at the 8q24 rs6983267 SNP; however, a major T allele SNP could more clearly reveal a correlation with CRC specifically when DM is present.
    Annals of Surgical Oncology 03/2012; 19(9):2853-8. · 4.12 Impact Factor
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    Hiromi Daiyasu, Wataru Nemoto, Hiroyuki Toh
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    ABSTRACT: Chemokine receptors (CKRs) function in the inflammatory response and in vertebrate homeostasis. Decoy and viral receptors are two types of CKR homologs with modified functions from those of the typical CKRs. The decoy receptors are able to bind ligands without signaling. On the other hand, the viral receptors show constitutive signaling without ligands. We examined the sites related to the functional difference. At first, the decoy and viral receptors were each classified into five groups, based on the molecular phylogenetic analysis. A multiple amino acid sequence alignment between each group and the CKRs was then constructed. The difference in the amino acid composition between the group and the CKRs was evaluated as the Kullback-Leibler (KL) information value at each alignment site. The KL information value is considered to reflect the difference in the functional constraints at the site. The sites with the top 5% of KL information values were selected and mapped on the structure of a CKR. The comparisons with decoy receptor groups revealed that the detected sites were biased on the intracellular side. In contrast, the sites detected from the comparisons with viral receptor groups were found on both the extracellular and intracellular sides. More sites were found in the ligand binding pocket in the analyses of the viral receptor groups, as compared to the decoy receptor groups. Some of the detected sites were located in the GPCR motifs. For example, the DRY motif of the decoy receptors was often degraded, although the motif of the viral receptors was basically conserved. The observations for the viral receptor groups suggested that the constraints in the pocket region are loose and that the sites on the intracellular side are different from those for the decoy receptors, which may be related to the constitutive signaling activity of the viral receptors.
    Frontiers in Microbiology 01/2012; 3:264. · 3.90 Impact Factor
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    ABSTRACT: Unlike conventional T cells, which are exported from the thymus as naive cells and acquire effector functions upon antigen encounter in the periphery, a subset of γδ T cells differentiates into effectors that produce IL-17 within the fetal thymus. We demonstrate here that intrathymic development of the naturally occurring IL-17-producing γδ T cells is independent of STAT3 and partly dependent on RORγt. Comparative gene-expression analysis identified Hes1, one of the basic helix-loop-helix proteins involved in Notch signaling, as a factor specifically expressed in IL-17-producing γδ T cells. Hes1 is critically involved in the development of IL-17-producing γδ T cells, as evidenced by their severe decrease in the thymi of Hes1-deficient fetal mice. Delta-like 4 (Dll4)-expressing stromal cells support the development of IL-17-producing γδ T cells in vitro. In addition, conditional Hes1 ablation in peripheral γδ T cells decreases their IL-17 production but not their IFN-γ production. These results reveal a unique differentiation pathway of IL-17-producing γδ T cells.
    Blood 05/2011; 118(3):586-93. · 9.78 Impact Factor
  • Wataru Nemoto, Kazuhiko Fukui, Hiroyuki Toh
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    ABSTRACT: The G protein Coupled Receptor (GPCR) superfamily is one of the most important pharmaceutical targets. Studies of GPCRs have long been performed under the assumption that GPCRs function as monomers. However, recent studies have revealed that many GPCRs function as homo- and/or hetero-dimers or higher-order oligomeric molecular complexes. As a result, information about GPCR oligomerization is rapidly accumulating, although the molecular mechanisms of oligomerization are not fully understood. A comprehensive collection of information about oligomerization would accelerate investigations of the molecular mechanisms of GPCRs' oligomerization and involvement in signaling. Hence, we have developed a database, G protein coupled Receptor Interaction Partners DataBase (GRIPDB), which provides information about GPCR oligomerization. The entries in the database are divided into two sections: (I) Experiment Information section and (II) Prediction Information section. The Experiment Information section contains (I-i) experimentally indentified GPCR oligomers and their annotations, and (I-ii) experimentally suggested interfaces for the oligomerization. Since the number of experimentally suggested interfaces is limited, the entries in the Prediction Information section have been introduced to provide information about the oligomerization interfaces predicted by our computational method. The experimentally suggested or computationally predicted interfaces are displayed by 3D graphics, using GPCRs with available coordinates. The information in the GRIPDB, especially that about the interfaces, is useful to investigate the molecular mechanisms of signal transduction via GPCR oligomerization. The GRIPDB is available on the web at the following URL: http://grip.cbrc.jp/GDB/index.html .
    Journal of Receptor and Signal Transduction Research 03/2011; 31(3):199-205. · 1.63 Impact Factor
  • Teppei Ebina, Hiroyuki Toh, Yutaka Kuroda
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    ABSTRACT: MOTIVATION: Biologically important proteins are often large, multidomain proteins, which are difficult to characterize by high-throughput experimental methods. Efficient domain/boundary predictions are thus increasingly required in diverse area of proteomics research for computationally dissecting proteins into readily analyzable domains. RESULTS: We constructed a support vector machine (SVM)-based domain linker predictor, DROP (Domain linker pRediction using OPtimal features), which was trained with 25 optimal features. The optimal combination of features was identified from a set of 3000 features using a random forest algorithm complemented with a stepwise feature selection. DROP demonstrated a prediction sensitivity and precision of 41.3 and 49.4%, respectively. These values were over 19.9% higher than those of control SVM predictors trained with non-optimized features, strongly suggesting the efficiency of our feature selection method. In addition, the mean NDO-Score of DROP for predicting novel domains in seven CASP8 FM multidomain proteins was 0.760, which was higher than any of the 12 published CASP8 DP servers. Overall, these results indicate that the SVM prediction of domain linkers can be improved by identifying optimal features that best distinguish linker from non-linker regions.
    Bioinformatics 02/2011; 27(4):487-94. · 5.47 Impact Factor
  • Chemistry and Physics of Lipids - CHEM PHYS LIPIDS. 01/2011; 164.
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    ABSTRACT: BLT2 is a low-affinity leukotriene B(4) (LTB(4)) receptor that is activated by 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) and LTB(4). Despite the well-defined proinflammatory roles of BLT1, the in vivo functions of BLT2 remain elusive. To clarify the role of BLT receptors in intestinal inflammation, we assessed susceptibility to dextran sodium sulfate (DSS)-induced colitis in mice lacking either BLT1 or BLT2. BLT2(-/-) mice exhibited increased sensitivity to DSS as compared to wild-type and BLT1(-/-) mice, with more severe body weight loss and inflammation. Expression of inflammatory cytokines such as interferon (IFN)-γ, interleukin (IL)-1β, and IL-6, chemokines such as CXC chemokine ligand 9 (CXCL9) and C-C motif chemokine 19 (CCL19), and metalloproteinases was highly up-regulated in the colons of DSS-treated BLT2(-/-) mice, and there was an enhanced accumulation of activated macrophages. Phosphorylation of the signal transducer and activator of transcription 3 (STAT3) was also markedly accelerated in the crypts of DSS-treated BLT2(-/-) mice. Madin-Darby canine kidney II (MDCKII) cells transfected with BLT2 exhibited enhanced barrier function as measured by transepithelial electrical resistance (TER) and FITC-dextran leakage through MDCK monolayers. Thus, BLT2 is expressed in colon cryptic cells and appears to protect against DSS-induced colitis, possibly by enhancing barrier function in epithelial cells of the colon. These novel results suggest a direct anti-inflammatory role of BLT2 that is distinct from the proinflammatory roles of BLT1.
    The FASEB Journal 12/2010; 24(12):4678-90. · 5.70 Impact Factor
  • Fredrik Johansson, Hiroyuki Toh
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    ABSTRACT: The Shannon entropy is a common way of measuring conservation of sites in multiple sequence alignments, and has also been extended with the relative Shannon entropy to account for background frequencies. The von Neumann entropy is another extension of the Shannon entropy, adapted from quantum mechanics in order to account for amino acid similarities. However, there is yet no relative von Neumann entropy defined for sequence analysis. We introduce a new definition of the von Neumann entropy for use in sequence analysis, which we found to perform better than the previous definition. We also introduce the relative von Neumann entropy and a way of parametrizing this in order to obtain the Shannon entropy, the relative Shannon entropy and the von Neumann entropy at special parameter values. We performed an exhaustive search of this parameter space and found better predictions of catalytic sites compared to any of the previously used entropies.
    Journal of Bioinformatics and Computational Biology 10/2010; 8(5):809-23. · 0.93 Impact Factor
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    Kazutaka Katoh, Hiroyuki Toh
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    ABSTRACT: SUMMARY: Multiple sequence alignment (MSA) is an important step in comparative sequence analyses. Parallelization is a key technique for reducing the time required for large-scale sequence analyses. The three calculation stages, all-to-all comparison, progressive alignment and iterative refinement, of the MAFFT MSA program were parallelized using the POSIX Threads library. Two natural parallelization strategies (best-first and simple hill-climbing) were implemented for the iterative refinement stage. Based on comparisons of the objective scores and benchmark scores between the two approaches, we selected a simple hill-climbing approach as the default. AVAILABILITY: The parallelized version of MAFFT is available at http://mafft.cbrc.jp/alignment/software/. This version currently supports the Linux operating system only.
    Bioinformatics 08/2010; 26(15):1899-900. · 5.47 Impact Factor
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    ABSTRACT: As recent technological innovations make it possible to clarify the concordant relationship between genomic alterations and aberrant gene expression during the progression of colorectal cancer (CRC), we aimed at identifying new overexpressing genes with genomic amplification on the responsible loci in CRC. The candidate gene was found using cDNA microarray and array-based comparative genomic hybridization (CGH) analysis after laser microdissection (LMD) in 132 Japanese CRC. We focused on SUGT1, which is associated with the assembling of kinetochore proteins at the metaphase of the cell cycle, with significant association between genetic alterations and expression. SUGT1 mRNA expression was evaluated in 98 CRC cases to determine the clinicopathological significance of SUGT1 expression. The mean level of SUGT1 mRNA expression in tumor tissue specimens was significantly higher than in non-tumor tissue. The high SUGT1 expression group was characterized by a significantly elevated frequency of recurrence and a significantly poorer prognosis than the low expression group. There was a significant association between poor prognosis of CRC cases and the overexpression of SUGT1 with genomic amplification of the loci concordantly. The amplification of SUGT1 might give rise to promote the transcription of the gene directly subsequent to the progression of CRC cases with worsening prognosis.
    International Journal of Oncology 03/2010; 36(3):569-75. · 2.66 Impact Factor
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    ABSTRACT: Lymph node metastasis is widely accepted as one of the most important determinants of prognosis in colorectal cancer (CRC) patients. Therefore, there is an urgent need to identify molecular markers that can be used to predict lymph node metastasis. Candidate genes were found using LMD and cDNA microarrays in a large-scale study of CRC, followed by Penalized Canonical Correlation Analysis (PCCA). We focused on the Fanconi anemia, complementation group D2 (FANCD2) gene and evaluated FANCD2 mRNA expression in 133 CRC cases to determine the clinicopathological significance of FANCD2 expression. The mean level of FANCD2 mRNA expression in tumor tissue specimens was significantly higher than in nontumor tissue. FANCD2 expression was found to be a significant factor affecting lymph node metastasis: the high FANCD2 expression group had a significantly poorer prognosis than the low expression group. This study suggests that PCCA can be used to identify genes related to clinicopathological features. Furthermore, high FANCD2 expression was a significant independent factor for lymph node metastasis.
    Annals of Surgical Oncology 03/2010; 17(9):2341-8. · 4.12 Impact Factor
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    ABSTRACT: MOTIVATION: Functional similarity between proteins is evident at both the sequence and structure levels. SeSAW is a web-based program for identifying functionally or evolutionarily conserved motifs in protein structures by locating sequence and structural similarities, and quantifying these at the level of individual residues. Results can be visualized in 2D, as annotated alignments, or in 3D, as structural superpositions. An example is given for both an experimentally determined query structure and a homology model. AVAILABILITY AND IMPLEMENTATION: The web server is located at http://www.pdbj.org/SeSAW/.
    Bioinformatics 03/2010; 26(9):1258-9. · 5.47 Impact Factor
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    ABSTRACT: Leukotriene C(4) (LTC(4)) is synthesized by binding of glutathione to LTA(4), an epoxide derived from arachidonic acid, and further metabolized to LTD(4) and LTE(4). We previously prepared a monoclonal antibody with a high affinity and specificity to LTC(4). To explore the structure of the antigen-binding site of a monoclonal antibody against LTC(4) (mAbLTC), we isolated full-length cDNAs for heavy and light chains of mAbLTC. The heavy and light chains consisted of 461 and 238 amino acids including a signal peptide with molecular weights of 51,089 and 26,340, respectively. An expression plasmid encoding a single-chain antibody comprising variable regions of mAbLTC heavy and light chains (scFvLTC) was constructed and expressed in COS-7 cells. The recombinant scFvLTC showed a high affinity with LTC(4) comparable to mAbLTC. The scFvLTC also bound to LTD(4) and LTE(4) with 48% and 17% reactivities, respectively, as compared with LTC(4) binding, whereas the antibody showed almost no affinity for LTB(4).
    Biochemical and Biophysical Research Communications 02/2010; 392(3):421-5. · 2.28 Impact Factor
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    Fredrik Johansson, Hiroyuki Toh
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    ABSTRACT: Conservation and variation scores are used when evaluating sites in a multiple sequence alignment, in order to identify residues critical for structure or function. A variety of scores are available today but it is not clear how different scores relate to each other. We applied 25 conservation and variation scores to alignments from the Catalytic Site Atlas (CSA). We calculated distances among scores based on correlation coefficients, and constructed a dendrogram of the scores by average linking cluster analysis. The cluster analysis showed that most scores fall into one of two groups--substitution matrix based group and frequency based group respectively. We also evaluated the scores' performance in predicting catalytic sites and found that frequency based scores generally perform best. Conservation and variation scores can be classified into mainly two large groups. When using a score to predict catalytic sites, frequency based scores that also consider a background distribution are most successful.
    BMC Bioinformatics 01/2010; 11:388. · 3.02 Impact Factor
  • Wataru Nemoto, Kazuhiko Fukui, Hiroyuki Toh
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    ABSTRACT: G-Protein Coupled Receptors (GPCRs) are one of the most important pharmaceutical targets. Recent studies have revealed that many GPCRs form homo- and/or hetero-oligomers. The molecular mechanisms of oligomerization are not fully understood yet, due to the lack of structural data for GPCR complexes. Therefore, accurate interface prediction would accelerate investigations of the molecular mechanisms of oligomerization and signaling via GPCRs. However, interface prediction for GPCR oligomerization is difficult, because the various GPCR subtypes often use different structural regions as their interfaces, even when the subtypes belong to the same subfamily. Previously, we developed a method to predict the interfaces for GPCR oligomerization, which overcomes the difficulty described above. We have now launched a web service, named G-protein coupled Receptors Interaction Partners (GRIP) ( http://grip.cbrc.jp/GRIP/index.html ), to predict the interfaces for GPCR oligomerization. As far as we know, it is the only service to predict the interfaces for GPCR oligomerization.
    Journal of Receptor and Signal Transduction Research 11/2009; 29(6):312-7. · 1.63 Impact Factor

Publication Stats

7k Citations
821.08 Total Impact Points

Institutions

  • 2013
    • Computational Biology Research Center
      Edo, Tōkyō, Japan
    • Gunma University
      • Graduate School of Medicine
      Maebashi-shi, Gunma-ken, Japan
  • 1998–2012
    • Kyushu University
      • • Medical Institute of Bioregulation - MIB Hospital
      • • Division of Bioinformatics
      Fukuoka-shi, Fukuoka-ken, Japan
    • Kumamoto University
      • Faculty of Education
      Kumamoto, Kumamoto Prefecture, Japan
  • 1991–2012
    • Osaka University
      • • Graduate School of Information Science and Technology
      • • Immunology Frontier Research Center
      • • Institute for Protein Research
      • • Department of Oral and Molecular Microbiology
      • • Research Institute for Microbial Diseases
      Ōsaka-shi, Osaka-fu, Japan
  • 2009–2011
    • National Institute of Advanced Industrial Science and Technology
      • Computational Biology Research Center
      Tokyo, Tokyo-to, Japan
  • 2008–2011
    • Tokyo University of Agriculture and Technology
      • Division of Biotechnology and Life Science
      Edo, Tōkyō, Japan
  • 2010
    • Kitasato University
      Edo, Tōkyō, Japan
  • 2005–2007
    • Nara Institute of Science and Technology
      • Graduate School of Information Science
      Ikoma, Nara, Japan
  • 2000–2006
    • Kyoto University
      • • Bioinformatics Center
      • • Radiation Biology Center
      Kyoto, Kyoto-fu, Japan
  • 2003–2005
    • The University of Tokyo
      • • Institute of Medical Science
      • • Center for Human Genome
      Tokyo, Tokyo-to, Japan
  • 1997
    • Kyushu Institute of Technology
      Hukuoka, Fukuoka, Japan
  • 1995–1997
    • Osaka Bioscience Institute
      Ōsaka, Ōsaka, Japan
  • 1991–1992
    • National Cerebral and Cardiovascular Center
      • Department of Cardiovascular Medicine
      Ōsaka, Ōsaka, Japan