A5066905666- Genomics, phytochemicals, and oxidative stress
- Epigenetics and DNA Methylation
- Glutathione Transferases and Polymorphisms
- Genetic Associations and Epidemiology
- Genomics and Rare Diseases
- Spaceflight effects on biology
- Hemoglobinopathies and Related Disorders
- Health, Environment, Cognitive Aging
- Radiomics and Machine Learning in Medical Imaging
- Kruppel-like factors research
- Bioinformatics and Genomic Networks
- Genomic variations and chromosomal abnormalities
- Genomics and Phylogenetic Studies
- Acute Myeloid Leukemia Research
- Exercise and Physiological Responses
- Molecular Biology Techniques and Applications
- Nutrition, Genetics, and Disease
- Image Processing and 3D Reconstruction
- RNA modifications and cancer
- Metabolomics and Mass Spectrometry Studies
- IL-33, ST2, and ILC Pathways
- Eosinophilic Disorders and Syndromes
- Protein Degradation and Inhibitors
- Mathematics, Computing, and Information Processing
- Chromosomal and Genetic Variations
Tohoku Medical Megabank Organization
2017-2024
Tohoku University
2015-2024
Tohoku Medical and Pharmaceutical University
2016-2017
The first step towards realizing personalized healthcare is to catalog the genetic variations in a population. Since dissemination of individual-level genomic information strictly controlled, it will be useful construct population-level allele frequency panels with easy-to-use interfaces. In Tohoku Medical Megabank Project, we sequenced nearly 4000 individuals from Japanese population and constructed an panel 3552 after removing related samples. called 3.5KJPNv2. It was by using standard...
Abstract In the Tohoku Medical Megabank project, genome and omics analyses of participants in two cohort studies were performed. A part data is available at Japanese Multi Omics Reference Panel (jMorp; https://jmorp.megabank.tohoku.ac.jp) as a web-based database, reported our previous manuscript published Nucleic Acid Research 2018. At that time, jMorp mainly consisted metabolome data; however, now genome, methylome, transcriptome have been integrated addition to enhancement number samples...
Modern medicine is increasingly focused on personalized medicine, and multi-omics data crucial in understanding biological phenomena disease mechanisms. Each ethnic group has its unique genetic background with specific genomic variations influencing risk drug response. Therefore, from populations are essential for the effective implementation of medicine. Various prospective cohort studies, such as UK Biobank, All Us Lifelines, have been conducted worldwide. The Tohoku Medical Megabank...
Significance Sickle cell disease (SCD) is one of the most common inherited disorders. A mutation in β-globin gene causes deformation red blood cells into a sickle shape, which turn intravascular hemolysis and vaso-occlusion resulting damage to multiple organs. Most studies that propose develop new SCD therapies include induction fetal γ-globin expression inhibit formation as their ultimate goal. In contrast, we demonstrate here activation nuclear factor erythroid 2-related 2 (Nrf2)...
Abstract The complete human genome sequence is used as a reference for next-generation sequencing analyses. However, some ethnic ancestries are under-represented in the (e.g., GRCh37) due to its bias toward European and African ancestries. Here, we perform de novo assembly of three Japanese male genomes using > 100× Pacific Biosciences long reads Bionano Genomics optical maps per sample. We integrate major allele consensus anchor scaffolds genetic radiation hybrid reconstruct each...
Personalized healthcare (PHC) based on an individual's genetic make-up is one of the most advanced, yet feasible, forms medical care. The Tohoku Medical Megabank (TMM) Project aims to combine population genomics, genetics and prospective cohort studies develop a critical infrastructure for establishment PHC. To date, TMM CommCohort (adult general population) BirThree Cohort (birth+three-generation families) have conducted recruitments baseline surveys. Genome analyses as part will aid in...
Abstract Space flight produces an extreme environment with unique stressors, but little is known about how our body responds to these stresses. While there are many intractable limitations for in-flight space research, some can be overcome by utilizing gene knockout-disease model mice. Here, we report deletion of Nrf2, a master regulator stress defense pathways, affects the health mice transported stay in International Station (ISS). After 31 days ISS, all returned safely Earth....
Nrf2 activates cytoprotective gene expression, and activity is regulated through at least two protein degradation pathways: the Keap1-mediated β-TrCP-mediated pathways. To address relative contributions of these pathways, we generated knock-in mouse lines expressing an Nrf2SA mutant that harbored substitution mutations serine residues interacting with β-TrCP. The homozygous (Nrf2SA/SA) mice grew normally, levels comparable to those wild-type (WT) under unstressed conditions. However, when...
Whole blood transcriptome analysis is a valuable approachin medical research, primarily due to the ease of sample collection and richness information obtained. Since expression profile individual genes in influenced by traits demographic attributes such as age gender, there has been growing demand for comprehensive database analysis. Here, we performed whole RNA sequencing (RNA-seq) on 576 participants stratified (20-30s 60-70s) gender from cohorts Tohoku Medical Megabank (TMM). A part...
The purpose of this study was to report the basic profile Miyagi Prefecture part a repeated center-based survey during second period Tohoku Medical Megabank Community-Based Cohort Study (TMM CommCohort Study), as well participants' characteristics based on their participation type in baseline survey.
A group of cytoprotective genes is regulated by heterodimers composed the cap'n'collar (CNC) family member Nrf2 and one small Maf (sMaf) proteins (MafF, MafG, or MafK) through antioxidant response element (ARE, also referred to as CNC-sMaf binding [CsMBE]). Many lines evidence support this model; however, a direct specific evaluation Nrf2-sMaf heterodimer remains be executed. To address issue, we constructed tethered Nrf2-MafG (T-N2G) using flexible linker peptide. We then introduced T-N2G...
Members of the cap'n'collar (CNC) family transcription factors, including Nrf1 and Nrf2, heterodimerize with small Maf (sMaf) proteins (MafF, MafG, MafK) regulate target gene expression through CNC-sMaf-binding elements (CsMBEs). We recently developed a unique tethered dimer assessment system combined triple-knockout fibroblasts, which enabled characterization specific CNC-sMaf heterodimer functions. In this study, we evaluated molecular function Nrf1-MafG (T-N1G) heterodimer. found that...
Spaceflight-related stresses impact health via various body systems, including the haematopoietic and immune with effects ranging from moderate alterations of homoeostasis to serious illness. Oxidative stress appears be involved in these changes, transcription factor Nrf2, which regulates expression a set cytoprotective antioxidative response genes, has been implicated spaceflight-induced stresses. Here, we show through analyses mice MHU-3 project, Nrf2-knockout travelled space for 31 days,...
Ethnic-specific SNP arrays are becoming more important to increase the power of genome-wide association studies in diverse population. In Tohoku Medical Megabank Project, we have been developing a series Japonica Arrays (JPA) for genotyping participants based on reference panels constructed from whole-genome sequence data Japanese Here, designed novel version array population, called Array NEO (JPA NEO), comprising total 666,883 markers. Among them, 654,246 tag SNPs autosomes and X...
Abstract Sickle cell disease (SCD) is caused by a monogenic mutation of the β-globin gene and affects millions people worldwide. SCD associated with sustained hemolytic anemia, vasoocclusion, ischemia-reperfusion injury, oxidative tissue damage, inflammatory activation, systemic endothelial dysfunction. The transcription factor Nrf2 coordinates expression wide variety genes encoding antioxidant, detoxification, metabolic enzymes. participates in suppressing proinflammatory cytokines organ...
Space travel induces stresses that contribute to health problems, as well inducing the expression of Nrf2 (NF-E2-related factor-2) target genes mediate adaptive responses oxidative and other stress responses. The volume epididymal white adipose tissue (eWAT) in mice increases during spaceflight, a change is attenuated by knockout. We conducted metabolome analyses plasma from wild-type knockout collected at pre-flight, in-flight post-flight time points, tissues clarify metabolic after...
GATA1 is a critical regulator of erythropoiesis. While the mechanisms underlying high-level expression in maturing erythroid cells have been studied extensively, initial activation Gata1 gene early hematopoietic progenitors remains to be elucidated. We previously identified stem and progenitor cell (HSPC)-specific silencer element (the methylation-determining region [G1MDR]) that recruits DNA methyltransferase 1 (Dnmt1) provokes methylation enhancer. In present study, we hypothesized removal...
GATA3 is a zinc finger transcription factor that plays crucial role in embryonic kidney development, while its precise functions the adult remain largely unexplored. Here, we demonstrate specifically expressed glomerular mesangial cells and critical maintenance of renal function. Newly generated Gata3 hypomorphic mutant mice exhibited neonatal lethality associated with severe hypoplasia. Normal size was restored by breeding rescuing transgenic mouse line bearing 662-kb yeast artificial...