A5086158311- Pharmacogenetics and Drug Metabolism
- Metabolomics and Mass Spectrometry Studies
- Biochemical and Molecular Research
- Drug Transport and Resistance Mechanisms
- Metabolism and Genetic Disorders
- Colorectal Cancer Treatments and Studies
- Pancreatic and Hepatic Oncology Research
- Diet and metabolism studies
- Bioinformatics and Genomic Networks
- Epigenetics and DNA Methylation
- Genomics, phytochemicals, and oxidative stress
- Computational Drug Discovery Methods
- Folate and B Vitamins Research
- Drug-Induced Hepatotoxicity and Protection
- Advanced Proteomics Techniques and Applications
- Eicosanoids and Hypertension Pharmacology
- Mass Spectrometry Techniques and Applications
- Cancer therapeutics and mechanisms
- Renal Transplantation Outcomes and Treatments
- Endometrial and Cervical Cancer Treatments
- Analytical Chemistry and Chromatography
- Health, Environment, Cognitive Aging
- Ubiquitin and proteasome pathways
- Fungal and yeast genetics research
- Xenotransplantation and immune response
Tohoku University
2015-2025
Tohoku Medical Megabank Organization
2018-2025
Center for Innovation
2022-2023
Meijo University
2020-2023
Hiroshima City University
2022-2023
Tohoku University Hospital
2018-2023
Showa Pharmaceutical University
2023
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...
Oxidative stress is an essential component in the progression of diabetic kidney disease (DKD), and transcription factor NF-E2-related factor-2 (Nrf2) plays critical roles protecting body against oxidative stress. To clarify Nrf2 DKD, this study we prepared compound mutant mice with diabetes loss antioxidative defense. Specifically, Ins2Akita/+ (Akita) knockout (Akita::Nrf2−/−) or Akita induction (Akita::Keap1FA/FA) mice. Eighteen-week-old Akita::Nrf2−/− showed more severe symptoms than In...
Activating mutations in KEAP1-NRF2 are frequently found tumors of the lung, esophagus, and liver, where they associated with aggressive growth, resistance to cancer therapies, low overall survival. Despite fact that NRF2 is a validated driver tumorigenesis chemotherapeutic resistance, there currently no approved drugs which can inhibit its activity. Therefore, an urgent clinical need identify NRF2-selective therapies. To this end, we developed novel synthetic lethal assay, based on...
Dihydropyrimidine dehydrogenase (DPD, EC 1.3.1.2), encoded by the <i>DPYD</i> gene, is rate-limiting enzyme in degradation pathway of endogenous pyrimidine and fluoropyrimidine drugs such as 5-fluorouracil (5-FU). DPD catalyzes reduction uracil, thymine, 5-FU. In Caucasians, mutations, including <i>DPYD*2A</i>, <i>DPYD*13</i>, c.2846A>T, c.1129-5923C>G/hapB3, are known to contribute interindividual variations toxicity 5-FU; however, none these polymorphisms has been identified Asian...
Lung cancer is the deadliest disease globally, with more than 120,000 diagnosed cases and 75,000 deaths annually in Japan. Several treatment options for advanced lung are available, discovery of biomarkers will be useful personalized medicine. Using metabolome analysis, we aimed to identify diagnosis response by examining changes metabolites associated progression. Plasma samples from patients recurrent or metastatic non-small cell carcinomas at Tohoku University Hospital between 2019 2024...
Ykt6 is a conserved SNARE protein involved in multiple membrane trafficking pathways, including intra-Golgi transport and autophagic fusion. We previously demonstrated that mammalian uniquely modified with farnesyl geranylgeranyl groups at two C-terminal cysteines through the sequential action of farnesyltransferase (FT) geranylgeranyltransferase type 3 (GGT3). Although these are strictly all eukaryotes, evolutionary conservation double prenylation remains unclear, as budding yeast appears...
<title>Abstract</title> Advancements in large-scale analysis of metabolites human peripheral blood samples revealed the links between metabolite concentrations and genetic variations. This field is known as metabolome-genome-wide association study (MGWAS). Although MGWAS a powerful tool, it has some limitations, particularly terms number that can be measured. Whether observed associations are directly due to variation or indirectly changes unmeasured unclear. To address this, we used...
CYP3A4 is among the most abundant liver and intestinal drug-metabolizing cytochrome P450 enzymes, contributing to metabolism of more than 30% clinically used drugs. Therefore, interindividual variability in activity a frequent cause reduced drug efficacy adverse effects. In this study, we characterized wild-type 40 variants, including 11 new detected 4773 Japanese individuals by assessing enzymatic activities for two representative substrates (midazolam testosterone). The carbon...
Dihydropyrimidine dehydrogenase (DPD), encoded by the DPYD gene, is rate-limiting enzyme in 5-fluorouracil (5-FU) degradation. In Caucasians, four risk variants are recognized to be responsible for interindividual variations development of 5-FU toxicity. However, these have not been identified Asian populations. Recently, 41 allelic variants, including 15 novel single nucleotide were 3,554 Japanese individuals analyzing their whole-genome sequences; however, effects on DPD enzymatic activity...
Abstract The evaluation of Cytochrome P450 (CYP) enzymatic activity is essential to estimate drug pharmacokinetics. Numerous CYP allelic variants have been identified; the functional characterisation these required for their application in precision medicine. Results from heterologous expression systems using mammalian cells can be integrated vivo studies; however, other such as E. coli , bacteria, yeast, and baculoviruses are generally used owing difficulty expressing high levels cells....
Epithelial ovarian cancer (EOC) is a fatal gynecologic cancer, and its poor prognosis mainly due to delayed diagnosis. Therefore, biomarker identification prediction are crucial in EOC. Altered cell metabolism characteristic feature of cancers, metabolomics reflects an individual’s current phenotype. In particular, plasma metabolome analyses can be useful for identification. this study, we analyzed 624 metabolites, including uremic toxins (UTx) derived from 80 patients with EOC using...
Accumulating data on the associations between food consumption and lipid composition in body is essential for understanding effects of dietary habits health.
Abstract Understanding the physiological changes associated with aging and disease risks is essential to establish biomarkers as indicators of biological aging. This study used NMR-measured plasma metabolome calculate age-specific metabolite indices. In doing so, scope was deliberately simplified capture general trends insights into age-related in metabolic patterns. addition, concentrations age were examined detail, period from 55–59 60–64 years being a significant change, particularly men,...
Dihydropyrimidinase (DHP) is the second enzyme in catabolic pathway of uracil, thymine, and chemotherapeutic fluoropyrimidine agents such as 5-fluorouracil (5-FU). Thus, DHP deficiency might be associated with 5-FU toxicity during chemotherapy. We performed genetic analyses family a patient advanced colon cancer who underwent radical colectomy followed by treatment prodrug capecitabine developed severe attributable to lack DHP. measured urinary uracil dihydrouracil, genotyped DPYS her...
Endometrial cancer (EMC) is the most common female genital tract malignancy with an increasing prevalence in many countries including Japan, a fact that renders early detection and treatment necessary to protect health fertility. Although are further improve prognosis of women endometrial cancer, biomarkers accurately reflect pathophysiology EMC patients still unclear. Therefore, it clinically critical identify assess diagnosis efficacy facilitate appropriate development new therapies for...
Metabolic profiling is an omics approach that can be used to observe phenotypic changes, making it particularly attractive for biomarker discovery. Although several candidate metabolites biomarkers disease expression have been identified in recent clinical studies, the reference values of healthy subjects not established. In particular, accuracy concentrations measured by mass spectrometry (MS) unclear. Therefore, comprehensive metabolic large-scale cohorts MS create a database with ranges...
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...
Single-nucleotide substitutions of human flavin-containing monooxygenase 3 (FMO3) identified in the whole-genome sequences updated Japanese population reference panel (now containing 38,000 subjects) were investigated. In this study, two stop codon mutations, frameshifts, and 43 amino-acid-substituted FMO3 variants identified. Among these 47 variants, one mutation, frameshift, 24 substituted already recorded National Center for Biotechnology Information database. Functionally impaired are...
Background and Aims: Cancer cells reprogram their metabolic pathways to support bioenergetic biosynthetic needs maintain redox balance. In several human tumors, the Keap1-Nrf2 system controls proliferation reprogramming by regulating pentose phosphate pathway (PPP). However, whether this also occurs in normal proliferating is unclear. Approach Results: To define phenotype hepatocytes, we induced cell liver 3 distinct stimuli: regeneration partial hepatectomy hepatic hyperplasia 2 direct...