A5033817054- Renal and related cancers
- Ion Transport and Channel Regulation
- Genetic and Kidney Cyst Diseases
- Enzyme Catalysis and Immobilization
- Biofuel production and bioconversion
- Microbial Metabolic Engineering and Bioproduction
- Cancer Cells and Metastasis
- Pancreatic function and diabetes
- Renal Diseases and Glomerulopathies
- Chemotherapy-induced organ toxicity mitigation
- Cancer, Hypoxia, and Metabolism
- Aortic aneurysm repair treatments
- Metabolism, Diabetes, and Cancer
- Cancer Mechanisms and Therapy
- Endometriosis Research and Treatment
- Reproductive System and Pregnancy
- Ovarian cancer diagnosis and treatment
- Peptidase Inhibition and Analysis
- Endometrial and Cervical Cancer Treatments
- Aortic Disease and Treatment Approaches
- Galectins and Cancer Biology
- Genetic Syndromes and Imprinting
- Fibroblast Growth Factor Research
- Vasculitis and related conditions
- Pediatric Urology and Nephrology Studies
Tokyo Medical and Dental University
2014-2025
Teikyo University
2023-2025
Niigata University
2017-2024
Kobe University
2023-2024
National Institute for Japanese Language and Linguistics
2024
The University of Tokyo
2016-2024
Niigata University Medical and Dental Hospital
2019-2024
Institute of Science Tokyo
2024
Brigham and Women's Hospital
2019-2023
Harvard University
2019-2023
Highlights•Endometriosis and uterine endometrium exhibit cancer-associated somatic mutations•Clonal expansion of epithelial cells with mutations in endometriosis•Genomic architecture is heterogeneous•Single endometrial glands carry distinct genesSummaryEndometriosis characterized by ectopic endometrial-like epithelium stroma, which molecular characteristics remain to be fully elucidated. We sequenced 107 ovarian endometriotic 82 normal samples isolated laser microdissection. In both samples,...
Background.In chronic kidney disease stage 5D, diagnostic usefulness of bone mineral density (BMD) in predicting fracture has not been established because variable results previous studies. The reason for this may be the heterogeneity underlying pathogenesis fracture.
Mutations in WNK kinases cause the human hypertensive disease pseudohypoaldosteronism type II (PHAII), but regulatory mechanisms of are not well understood. kelch-like 3 (KLHL3) and Cullin3 were also recently identified as causing PHAII. Therefore, new insights into hypertension can be gained by determining how these components interact they involved pathogenesis Here, we found that KLHL3 interacted with WNK4, induced WNK4 ubiquitination, reduced protein level. The interaction PHAII-causing...
The fundamental morphology of the endometrial glands is not sufficiently understood by 2D observation because these have complicated winding and branching patterns. To construct a large picture gland structure, we performed tissue-clearing-based 3D imaging human uterine tissue. Our immunohistochemistry layer analyses revealed that form plexus network in stratum basalis expand horizontally along muscular layer, similar to rhizome grass. We then extended our method assess tissue affected...
Maladaptive proximal tubule (PT) repair has been implicated in kidney fibrosis through induction of cell-cycle arrest at G2/M. We explored the relative importance PT DNA damage response (DDR) by genetically inactivating ataxia telangiectasia and Rad3-related (ATR), which is a sensor upstream initiator DDR. In human chronic disease, ATR expression inversely correlates with damage. was upregulated approximately 70% Lotus tetragonolobus lectin-positive (LTL+) cells cisplatin-exposed organoids....
This review introduces the importance of controlled colloidal NPs/NCs in research on water-splitting photocatalysis by summarizing existing research.
Uterine endometrial cancer is associated with poor survival outcomes in patients advanced-stage disease. Here, we developed a three-dimensional cell cultivation method of endometrioid stem-like cells high aldehyde dehydrogenase (ALDH) activity from clinical specimens. ALDH inhibition synergized paclitaxel to block proliferation. In the setting, ALDH1A1 expression was survival. A level correlated an increase glucose uptake, activation glycolytic pathway, and elevation transporter 1 (GLUT1)....
Phenotypic alterations in the lung epithelium have been widely implicated chronic obstructive pulmonary disease (COPD) pathogenesis, but precise mechanisms orchestrating this persistent inflammatory process remain unknown because of complexity parenchymal and mesenchymal architecture. To identify cell type–specific cell–cell interactions among multiple resident types cells that contribute to COPD progression, we profiled 57,918 from lungs patients with COPD, smokers without never-smokers...
Ovarian clear cell carcinoma (OCCC) is a gynecological cancer with dismal prognosis; however, the mechanism underlying OCCC chemoresistance not well understood. To explore intracellular networks associated chemoresistance, we analyze surgical specimens by performing integrative analyses that combine single-cell and spatial transcriptomics. We find chemoresistant subpopulation elevated HIF activity localizes mainly in areas populated cancer-associated fibroblasts (CAFs) myofibroblastic...
Pseudohypoaldosteronism type II (PHAII) is a hereditary disease characterized by salt-sensitive hypertension, hyperkalemia and metabolic acidosis, genes encoding with-no-lysine kinase 1 (WNK1) WNK4 kinases are known to be responsible. Recently, Kelch-like 3 (KLHL3) Cullin3, components of KLHL3-Cullin3 E3 ligase, were newly identified as responsible for PHAII. We have reported that the substrate ligase-mediated ubiquitination. However, WNK1 Na–Cl cotransporter (NCC) also ligase other groups....
Dietary potassium intake is inversely related to blood pressure and mortality. Moreover, the sodium-chloride cotransporter (NCC) plays an important role in regulation urinary excretion response intake. Previously, it was shown that NCC activated by WNK4-SPAK cascade dephosphorylated protein phosphatase. However, mechanism of with acute still unclear. To identify molecular intake, we used adult C57BL/6 mice fed a 1.7% solution oral gavage. We confirmed load rapidly NCC, which not dependent on...
The activity of many water-splitting photocatalysts could be improved by the use RhIII -CrIII mixed oxide (Rh2-x Crx O3 ) particles as cocatalysts. Although further improvement achieved if size Rh2-x was decreased further, it is difficult to load ultrafine (<2 nm) onto a photocatalyst using conventional loading methods. In this study, new method successfully established and used with approximately 1.3 nm narrow distribution BaLa4 Ti4 O15 photocatalyst. obtained exhibited an apparent quantum...
Abstract SARS-CoV-2 precipitates respiratory distress by infection of airway epithelial cells and is often accompanied acute kidney injury. We report that Kidney Injury Molecule-1/T cell immunoglobulin mucin domain 1 (KIM-1/TIM-1) expressed in lung COVID-19 patients a receptor for SARS-CoV-2. Human mouse express KIM-1 endocytose nanoparticles displaying the spike protein (virosomes). Uptake was inhibited anti-KIM-1 antibodies TW-37, newly discovered inhibitor KIM-1-mediated endocytosis....
It has become evident that somatic mutations in cancer-associated genes accumulate the normal endometrium, but spatiotemporal understanding of evolution and expansion mutant clones is limited. To elucidate timing mechanism clonal we sequence 1311 endometrial glands from 37 women. By collecting different parts show multiple with same occupy substantial areas endometrium. We demonstrate "rhizome structures", which basal run horizontally along muscular layer vertical rise gland, originate...
We previously found that therapeutic targetable fusions are detected across various cancers. To identify fusion in uterine cervical cancer, for which no effective gene targeted therapy has yet been clinically applied, we analyzed RNA sequencing data from 306 cancer samples. 445 high confidence transcripts and identified four samples harbored FGFR3-TACC3 as an attractive target. The frequency of FGFR3-TACC3-fusion-positive is also 1.9% (2/103) independent cohort. Continuous expression the...
Mutations in the with-no-lysine kinase 1 (WNK1), WNK4, kelch-like 3 (KLHL3), and cullin3 (CUL3) genes are known to cause hereditary disease pseudohypoaldosteronism type II (PHAII). It was recently demonstrated that this results from defective degradation of WNK1 WNK4 by KLHL3/CUL3 ubiquitin ligase complex. However, other physiological vivo roles KLHL3 remain unclear. Therefore, here we generated KLHL3−/− mice expressed β-galactosidase (β-Gal) under control endogenous promoter. Immunoblots...
We explored the frequency of germline and somatic mutations in homologous recombination (HR)-associated genes major histological types ovarian cancer. performed targeted sequencing to assess 16 HR-associated 4 mismatch repair (MMR) among 207 cancer patients (50 high-grade serous carcinomas (HGSC), 99 clear cell (CCC), 39 endometrioid (EC), 13 mucinous (MC), 6 low-grade (LGSC)). Germline or were detected 44% HGSC, 28% CCC, 23% EC, 16% MC, 17% LGSC patients. The profile gene was remarkably...
Abstract The C4 unsaturated compound 1,3-butadiene is an important monomer in synthetic rubber and engineering plastic production. However, microorganisms cannot directly produce when glucose used as a renewable carbon source via biological processes. In this study, we construct artificial metabolic pathway for production from Escherichia coli by combining the cis,cis -muconic acid ( cc MA)-producing together with tailored ferulic decarboxylase mutations. rational design of substrate-binding...
Patient-derived cells and xenografts retain the biological characteristics of clinical cancers are instrumental in gaining a better understanding chemoresistance cancer cells. Here, we have established panel patient-derived spheroids from materials ovarian cancer. Systematic evaluation using therapeutic agents indicated that sensitivity to platinum-based compounds significantly varied among spheroids. To understand molecular basis drug sensitivity, performed integrative analyses combining...
Aging | doi:10.18632/aging.205164. Hisazumi Matsuki, Shintaro Mandai, Hiroki Shiwaku, Takaaki Koide, Naohiro Takahashi, Tomoki Yanagi, Shunsuke Inaba, Saaya Ida, Tamami Fujiki, Yutaro Mori, Fumiaki Ando, Takayasu Koichiro Susa, Soichiro Iimori, Eisei Sohara, Hidehiko Shinichi Uchida
Organoids are miniature organs developed through technology. Kidney organoids that originate from human inducible pluripotent stem cells (iPSCs) were to recreate renal diseases. However, it is impossible simultaneously produce kidney iPSCs of multiple individuals and in a single medium. We herein report the development adult tubular organoids, namely, "tubuloids," primary epithelial Kidneys eight patients who underwent nephrectomy due malignancy sectioned, tubule cultured; four had normal...
ABSTRACT Squamous cell carcinoma arising from mature teratoma (SCC‐MT) is a rare ovarian malignancy. The detailed molecular pathology of SCC‐MT not well understood. Moreover, the prognosis patients remains poor because no standard treatment has been established. In this study, we performed single‐nucleus RNA sequencing and spatial transcriptomics using clinical samples to identify novel therapeutic candidates. snRNA‐seq revealed three epithelial clusters, which one was significantly...