A5057044610- Liver Diseases and Immunity
- Liver Disease Diagnosis and Treatment
- Pediatric Hepatobiliary Diseases and Treatments
- Bioinformatics and Genomic Networks
- Gene Regulatory Network Analysis
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Gene expression and cancer classification
- Epigenetics and DNA Methylation
- Retinal Development and Disorders
- MicroRNA in disease regulation
- Pluripotent Stem Cells Research
- RNA modifications and cancer
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Cancer-related molecular mechanisms research
- Immunodeficiency and Autoimmune Disorders
- Genetics, Aging, and Longevity in Model Organisms
- Cancer-related Molecular Pathways
- Systemic Lupus Erythematosus Research
- Genetic factors in colorectal cancer
- Microbial Metabolic Engineering and Bioproduction
- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- Renal Diseases and Glomerulopathies
- Connective tissue disorders research
National Center for Global Health and Medicine
2020-2024
The University of Tokyo
2008-2022
Tohoku Medical Megabank Organization
2013-2022
Tohoku University
2012-2022
Nihon University
2020
Tokyo University of Science
2003-2012
Universidade de São Paulo
2011
RIKEN BioResource Research Center
2010
Purpose To identify stage I lung adenocarcinoma patients with a poor prognosis who will benefit from adjuvant therapy. Patients and Methods Whole gene expression profiles were obtained at 19 time points over 48-hour course human primary epithelial cells that stimulated epidermal growth factor (EGF) in the presence or absence of clinically used EGF receptor tyrosine kinase (RTK)-specific inhibitor, gefitinib. The data subjected to mathematical simulation using State Space Model (SSM)....
To understand the genetics of steroid-sensitive nephrotic syndrome (SSNS), we conducted a genome-wide association study in 987 childhood SSNS patients and 3,206 healthy controls with Japanese ancestry. Beyond known associations HLA-DR/DQ region, common variants NPHS1-KIRREL2 (rs56117924, P=4.94E-20, odds ratio (OR) =1.90) TNFSF15 (rs6478109, P=2.54E-8, OR=0.72) regions achieved significance were replicated Korean, South Asian African populations. Trans-ethnic meta-analyses including...
Neural stem cells (NSCs) are considered to be the cell of origin glioblastoma multiforme (GBM). However, genetic alterations that transform NSCs into glioma-initiating remain elusive. Using a unique transposon mutagenesis strategy mutagenizes in culture, followed by additional rounds generate tumors vivo, we have identified genes and signaling pathways can cells. Mobilization Sleeping Beauty transposons induced immortalization astroglial-like cells, which were then able with characteristics...
Neurodegeneration has been shown to induce microglial activation and the infiltration of monocyte‐derived macrophages into CNS, resulting in coexistence these two populations within same lesion, though their distinct features remain elusive. To investigate impact rod photoreceptor degeneration on activation, we generated a toxin‐mediated genetic model degeneration. Rod injury induced proliferation migration toward photoreceptors. Bone marrow transplantation revealed invasion retina, with...
Abstract Background Model checking approaches were applied to biological pathway validations around 2003. Recently, Fisher et al . have proved the importance of model approach by inferring new regulation signaling crosstalk in C. elegans and confirming with experiments. They took a discrete state-based explore all possible states system underlying vulval precursor cell (VPC) fate specification for desired properties. However, since both continuous features appear be an indispensable part...
The derivation of induced pluripotent stem (iPS) cells from individuals genetic disorders offers new opportunities for basic research into these diseases and the development therapeutic compounds. Severe congenital neutropenia (SCN) is a serious disorder characterized by severe at birth. SCN associated with heterozygous mutations in neutrophil elastase [elastase, neutrophil-expressed (ELANE)] gene, but mechanisms that disrupt have not yet been clarified because current lack an appropriate...
Abstract To analyze cell lineage-specific transitions in global transcriptional and epigenetic changes during retinogenesis, we purified retinal cells from normal mice postnatal development into two fractions, namely, photoreceptors other cells, based on Cd73 expression, performed RNA sequencing ChIP of H3K27me3 H3K4me3. Genes expressed the photoreceptor lineage were marked with H3K4me3 Cd73-positive fraction; however, level was very low both -negative populations. may be involved...
Primary biliary cholangitis (PBC) is a chronic and cholestatic autoimmune liver disease caused by the destruction of intrahepatic small bile ducts. Our previous genome-wide association study (GWAS) identified six susceptibility loci for PBC. Here, in order to further elucidate genetic architecture PBC, GWAS was performed on an additional independent sample set, then meta-analysis with our based whole-genome single nucleotide polymorphism (SNP) imputation analysis total 4,045 Japanese...
Recent studies have documented various roles of adrenal corticosteroid signaling in cardiac physiology and pathophysiology. It is known that glucocorticoids aldosterone are able to bind glucocorticoid receptor (GR) mineralocorticoid receptor, these ligand-receptor interactions redundant. It, therefore, has been impossible delineate how nuclear receptors couple with ligands differentially regulate gene expression for operation their distinct functions the heart. Here, particularly define role...
Using quantitative PCR-based miRNA arrays, we comprehensively analyzed the expression profiles of miRNAs in human and mouse embryonic stem (ES), induced pluripotent (iPS), somatic cells. Immature cells were purified using SSEA-1 or SSEA-4 used for profiling. Hierarchical clustering consensus by nonnegative matrix factorization showed two major clusters, ES/iPS other cell groups, as previously reported. Principal components analysis (PCA) to identify that segregate these groups identified...
Recent advances have enabled the direct induction of human tissue-specific stem and progenitor cells from differentiated somatic cells. However, it is not known whether hepatic (hHepPCs) can be generated other cell types by lineage reprogramming with defined transcription factors. Here, we show that a set three factors, FOXA3, HNF1A, HNF6, induce umbilical vein endothelial to directly acquire properties hHepPCs. These induced hHepPCs (hiHepPCs) propagate in long-term monolayer culture...
We propose a state space representation of vector autoregressive model and its sparse learning based on L1 regularization to achieve efficient estimation dynamic gene networks time course microarray data. The proposed method can overcome drawbacks the model; assumption equal interval lack separation ability observation systems noises in former modularity network structure latter method. However, simple implementation requires calculation large inverse matrices number times during parameter...
Retinal neurons and Müller glia are generated from a common population of multipotent retinal progenitor cells. We purposed to identify glia-specific molecular signatures during development. Using transgenic mice carrying the Hes1 promoter (pHes1) followed by EGFP, we purified EGFP-positive other EGFP-negative cells developing retinas subjected them RNA sequencing analysis. Gene expression pattern cell was similar genes expressed in progenitors, they were downregulated lineages. Then,...
BRCA1-associated protein 1 (BAP1) is a deubiquitinating enzyme that involved in the regulation of cell growth. Recently, many somatic and germline mutations BAP1 have been reported broad spectrum tumors. In this study, we identified novel non-synonymous mutation, phenylalanine-to-isoleucine substitution at codon 170 (F170I), 49 patients with esophageal squamous carcinoma (ESCC). Multiplex ligation-dependent probe amplification (MLPA) gene ESCC tumor disclosed monoallelic deletion (LOH),...
Genome-wide association studies (GWASs) in European and East Asian populations have identified more than 40 disease-susceptibility genes primary biliary cholangitis (PBC). The aim of this study is to computationally identify disease pathways, upstream regulators, therapeutic targets PBC through integrated GWAS messenger RNA (mRNA) microarray analysis. Disease pathways regulators were analyzed with ingenuity pathway analysis data set 1 for GWASs (1,920 patients 1,770 controls), which included...
Abstract Background and Aim Patients with inflammatory bowel disease (IBD) are at a high risk of low bone mineral density (BMD). Reportedly, clinical genetic factors cause BMD in Caucasians; however, studies non‐Caucasian populations remain scarce. Methods Clinical for were investigated 266 Japanese patients IBD, genome‐wide association analysis (GWAS) was performed using linear regression associated as covariates. Genotyping population‐optimized genotyping array (Japonica ® ). After quality...
Abstract Background Ligation of CD28 with ligands such as CD80 or CD86 provides a critical second signal alongside antigen presentation by class II major histocompatibility complex expressed on antigen-presenting cells through the T cell receptor for naïve activation. A number studies suggested that plays an important role in pathogenesis various human diseases. Recent genome-wide association (GWASs) identified susceptibility locus lymphocyte and eosinophil counts, multiple sclerosis,...
Primary biliary cholangitis (PBC) is a rare autoimmune disease with clear predisposition for human leukocyte antigen (HLA)-DR/DQ -associated loss of immune tolerance the E2 component pyruvate dehydrogenase complex. Three-field-resolution HLA imputation 1,670 Japanese PBC patients and 2,328 healthy controls was conducted using population-specific reference panels. Eighteen previously reported PBC-associated alleles were confirmed extended to 3-field-resolution, including HLA-DRB1*08:03...
Primary biliary cholangitis (PBC) is a chronic, progressive cholestatic liver disease in which intrahepatic bile ducts are destroyed by an autoimmune reaction. Our previous genome-wide association study (GWAS) identified chromosome 11q23.1 as susceptibility gene locus for PBC the Japanese population. Here, high-density mapping based on single nucleotide polymorphism (SNP) imputation and silico/in vitro functional analyses rs1944919 primary variant. Expression-quantitative trait loci showed...