A5037085615- Cellular transport and secretion
- Lipid Membrane Structure and Behavior
- Hippo pathway signaling and YAP/TAZ
- Neuroinflammation and Neurodegeneration Mechanisms
- Erythrocyte Function and Pathophysiology
- Gut microbiota and health
- Nanoplatforms for cancer theranostics
- Phagocytosis and Immune Regulation
- Immune cells in cancer
- Cancer-related Molecular Pathways
- Glycosylation and Glycoproteins Research
- Wnt/β-catenin signaling in development and cancer
- Biochemical effects in animals
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Peptidase Inhibition and Analysis
- RNA Interference and Gene Delivery
- Digestive system and related health
- Glioma Diagnosis and Treatment
- Tryptophan and brain disorders
- Cancer Research and Treatments
- Single-cell and spatial transcriptomics
- Ocular Oncology and Treatments
- bioluminescence and chemiluminescence research
- Immune Response and Inflammation
- Ubiquitin and proteasome pathways
Massachusetts General Hospital
2024
Harvard University
2024
Osaka University
2020-2023
University of Tokyo Health Sciences
2013-2023
University of Freiburg
2022
The University of Tokyo
2015-2017
Abstract Although cellular senescence acts primarily as a tumour suppression mechanism, the accumulation of senescent cells in vivo eventually exerts deleterious side effects through inflammatory/tumour-promoting factor secretion. Thus, development new drugs that cause specific elimination cells, termed senolysis, is anticipated. Here, by an unbiased high-throughput screening chemical compounds and bio-functional analysis, we identify BET family protein degrader (BETd) promising senolytic...
Emerging evidence is revealing that alterations in gut microbiota are associated with colorectal cancer (CRC). However, very little currently known about whether and how causally CRC development. Here we show 12 faecal bacterial taxa enriched patients two independent cohort studies. Among them, 2 Porphyromonas species capable of inducing cellular senescence, an oncogenic stress response, through the secretion metabolite, butyrate. Notably, invasion these bacteria observed tissues, coinciding...
Cellular senescence, a state of irreversible cell-cycle arrest caused by variety cellular stresses, is critically involved in age-related tissue dysfunction various organs. However, the features cells central nervous system that undergo senescence and their role neural impairment are not well understood as yet. Here, through comprehensive investigations utilising single-cell transcriptome analysis mouse models, we show microglia, particularly white matter, brain spinal cord during ageing...
P4-ATPases translocate aminophospholipids, such as phosphatidylserine (PS), to the cytosolic leaflet of membranes. PS is highly enriched in recycling endosomes (REs) and essential for endosomal membrane traffic. Here, we show that flipping by an RE-localized P4-ATPase required recruitment fission protein EHD1. Depletion ATP8A1 impaired asymmetric transbilayer distribution REs, dissociated EHD1 from generated aberrant tubules appear resistant fission. did not localization cells defective...
Abstract Reports of post-acute COVID-19 syndrome, in which the inflammatory response persists even after SARS-CoV-2 has disappeared, are increasing 1 , but underlying mechanisms syndrome remain unknown. Here, we show that SARS-CoV-2-infected cells trigger senescence-like cell-cycle arrest 2,3 neighboring uninfected a paracrine manner via virus-induced cytokine production. In cultured human or bronchial organoids, these SASR-CoV-2 infection-induced senescent express high levels series factors...
Yes-associated protein (YAP) is a recently discovered growth-promoting transcription coactivator that has been shown to regulate the malignancy of various cancers. How YAP regulated not fully understood. Here, we show one factors regulating phosphatidylserine (PS) in recycling endosomes (REs). We use proximity biotinylation find proteins proximal PS. Among these are and multiple related signalling. Knockdown ATP8A1 (an RE PS-flippase) or evectin-2 RE-resident protein) masking PS cytoplasmic...
The retrograde pathway is defined by the transport of proteins and lipids from plasma membrane (PM) through endosomes to Golgi, essential for a variety cellular activities. Recycling (REs) are important sorting stations some cargo. SMAP2, an Arf GTPase-activating protein (GAP) Arf1, with putative clathrin-binding domain was previously shown participate in CTxB REs. Here we found that clathrin, vesicle coat protein, clathrin adaptor complex 1 (AP-1) were present at REs needed cholera toxin B...
Yes-associated protein (YAP) is a transcriptional coactivator that essential for the malignancy of various cancers. We have previously shown YAP activity positively regulated by phosphatidylserine (PS) in recycling endosomes (REs). However, mechanism which activated PS REs remains unknown. In present study, we examined group phosphatases (11 phosphatases) had identified as PS-proximity candidates. Knockdown experiments these suggested PPP1R12A, regulatory subunit myosin phosphatase complex,...
Retrograde transport is where proteins and lipids are transported back from the plasma membrane (PM) endosomes to Golgi, crucial for a diverse range of cellular functions. Recycling (REs) serve as sorting station retrograde we recently identified evection-2, an RE protein with pleckstrin homology (PH) domain, essential factor this pathway. How evection-2 regulates REs Golgi not well understood. Here, report that binds SMAP2, Arf GTPase-activating protein. Endogenous SMAP2 localized mostly in...
Abstract Glioblastoma stem cells (GSCs) are potent tumor initiators resistant to radiochemotherapy, and this subpopulation is hypothesized re‐populate the milieu due selection following conventional therapies. Here, we show that 5‐aminolevulinic acid (ALA) treatment—a pro‐fluorophore used for fluorescence‐guided cancer surgery—leads elevated levels of fluorophore conversion in patient‐derived GSC cultures, subsequent red light‐activation induces apoptosis both intrinsically temozolomide...
Standard chemoradiation often enriches drug-resistant tumor cell populations that can lead to recurrent and treatment-refractory disease. Preclinical models of glioblastoma brain tumors, for instance, suggest the cancer stem subpopulation becomes enriched re-populates milieu following conventional therapies. Here, we show evidence photodynamic therapy (PDT) is effective against several patient-derived cultures. Moreover, sub-lethal PDT results in re-sensitization phenotypes with induced...