A5073017471- Renal and related cancers
- Chronic Kidney Disease and Diabetes
- Liver Disease Diagnosis and Treatment
- Renal Diseases and Glomerulopathies
- Diet, Metabolism, and Disease
- Diet and metabolism studies
- Metabolism and Genetic Disorders
- Birth, Development, and Health
- Cancer, Hypoxia, and Metabolism
- Pancreatic function and diabetes
- Dialysis and Renal Disease Management
- Tryptophan and brain disorders
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Renal and Vascular Pathologies
- Peroxisome Proliferator-Activated Receptors
- Health, Environment, Cognitive Aging
- Single-cell and spatial transcriptomics
- Mitochondrial Function and Pathology
- Inflammasome and immune disorders
- Folate and B Vitamins Research
- Mast cells and histamine
- Psoriasis: Treatment and Pathogenesis
- Genetic and Kidney Cyst Diseases
- Chemical Reactions and Isotopes
Nagoya University
2016-2025
University of Pennsylvania
2020-2025
Children's Hospital of Philadelphia
2024
Institute of Nutrition, Metabolism and Diabetes
2021-2023
Fujita Health University
2016
Japanese Red Cross Nagoya Daiichi Hospital
2012
The kidney has tremendous capacity to repair after acute injury, however, pathways guiding adaptive and fibrotic are poorly understood. We developed a model of regeneration by titrating ischemic injury dose. performed detailed biochemical histological analysis profiled transcriptomic changes at bulk single-cell level (> 110,000 cells) over time. Our highlights proximal tubule cells as key susceptible injury. Adaptive correlated with fatty acid oxidation oxidative phosphorylation. identify...
Genome-wide association studies (GWAS) for kidney function identified hundreds of risk regions; however, the causal variants, target genes, cell types, and disease mechanisms remain poorly understood. Here, we performed transcriptome-wide (TWAS), summary Mendelian randomization, MetaXcan to identify genes whose expression mediates genotype effect on phenotype. Our analyses Dachshund homolog 1 (DACH1), a cell-fate determination factor. GWAS variant was associated with lower DACH1 in human...
Significance Statement Although gene expression changes have been characterized in human diabetic kidney disease (DKD), unbiased tissue proteomics information for this condition is lacking. The authors conducted an aptamer-based proteomic analysis of samples from patients with DKD and healthy controls, identifying proteins levels that associate function (eGFR) or fibrosis, after adjusting key covariates. Overall, only modestly correlated protein levels. Kidney RNA matrix metalloproteinase 7...
Worldwide, over 800 million people are affected by kidney disease, yet its pathogenesis remains elusive, hindering the development of novel therapeutics. In this study, we employed kidney-specific expression quantitative traits and single-nuclear open chromatin analysis to show that genetic variants linked dysfunction on chromosome 20 target acyl-CoA synthetase short-chain family 2 (ACSS2). By generating ACSS2 knock-out mice, demonstrated their protection from fibrosis in multiple disease...
Mineralocorticoid excess commonly leads to hypertension and kidney disease. In our study, we employed single-cell expression chromatin accessibility tools characterize the mineralocorticoid target genes cell types. We demonstrated that effects are established through open gene expression, primarily in principal connecting tubule cells, a lesser extent, segments of distal convoluted cells. examined kidney-protective steroidal non-steroidal antagonists (MRAs), as well amiloride, an epithelial...
Dachshund homolog 1 (DACH1), a key cell-fate determinant, regulates transcription by DNA sequence–specific binding. We identified diminished Dach1 expression in large-scale screen for mutations that convert injury-resistant podocytes into injury-susceptible podocytes. In diabetic kidney disease (DKD) patients, podocyte DACH1 levels are diminished, condition strongly correlates with poor clinical outcomes. Global KO mice manifest renal hypoplasia and die perinatally. Podocyte-specific mice,...
Aging-associated kidney disease is usually considered a degenerative process associated with aging. Recently, it has been shown that animals can produce fructose endogenously, and this be mechanism for causing damage in diabetic nephropathy association recurrent dehydration. We therefore hypothesized low-level metabolism of endogenous might play role aging-associated disease. Wild-type fructokinase knockout mice were fed normal diet 2 yr had minimal (<5%) content. At the end yr, wild-type...
Genome-wide association studies (GWASs) have identified more than 1000 loci where genetic variants correlate with kidney function. However, the specific genes, cell types, and mechanisms influenced by these remain largely uncharted. Here, we glutathione-specific gamma–glutamylcyclotransferase 1 ( CHAC1 ) on chromosome 15 as affected GWAS analyzing human gene expression methylation information. Both RNA protein were expressed in loop of Henle region mouse kidneys, was higher patients carrying...
Dipeptides have attracted much attention as post-amino acids with physical properties and functions different from those of amino acids. However, a given dipeptide cannot be distinguished by mass spectrometry its structural isomer an opposite acid binding order unless these isomers are separated before introduction, which complicates the comprehensive analysis dipeptides. Herein, novel analytical platform for capillary electrophoresis tandem liquid chromatography is developed. This method...
Integrated omics analysis (GWAS, eQTL, snATAC, and mouse genetic models) identified caspase-9 as a kidney disease risk gene.
Renal interstitial fibrosis (RIF) is a common pathological manifestation of chronic kidney diseases. Epithelial-mesenchymal transition (EMT) tubular epithelial cells considered major cause RIF. Although long non-coding RNAs (lncRNAs) are reportedly involved in various pathophysiological processes, the roles and underlying molecular mechanisms lncRNAs progression RIF poorly understood. In this study, we investigated function Microarray assays showed that expression lncRNA lnc-CHAF1B-3 (also...