A5056333431- Advanced Fluorescence Microscopy Techniques
- Nanoplatforms for cancer theranostics
- Click Chemistry and Applications
- Advanced Biosensing Techniques and Applications
- Photoreceptor and optogenetics research
- Advanced Electron Microscopy Techniques and Applications
- Advanced biosensing and bioanalysis techniques
- Image Processing Techniques and Applications
- Cancer Research and Treatments
- Neuroscience and Neuropharmacology Research
- Adenosine and Purinergic Signaling
- Luminescence and Fluorescent Materials
- Cellular transport and secretion
- Retinal Development and Disorders
- Biotin and Related Studies
- Molecular Sensors and Ion Detection
- Receptor Mechanisms and Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- 14-3-3 protein interactions
- ATP Synthase and ATPases Research
- Cell Image Analysis Techniques
- Photodynamic Therapy Research Studies
- Cellular Mechanics and Interactions
- bioluminescence and chemiluminescence research
- Lysosomal Storage Disorders Research
The University of Tokyo
2012-2024
Graco (United States)
2019-2023
Japan Science and Technology Agency
2009-2021
Graduate School USA
2020
Tokyo Medical University
2018
The Open University of Japan
2014
Harvard–MIT Division of Health Sciences and Technology
2011
Massachusetts General Hospital
2011
A spirocyclic-caged, small-molecule imaging probe fluoresces upon cleavage by a cancer-specific enzyme and can be used during surgical or endoscopic tumor removal procedures.
Abstract Fluorescence-guided diagnostics is one of the most promising approaches for facile detection cancer in situ . Here we focus on β-galactosidase, which overexpressed primary ovarian cancers, as a molecular target visualizing peritoneal metastases from cancers. As existing fluorescence probes are unsuitable, have designed membrane-permeable HMRef-βGal, optimized intramolecular spirocyclic function affords >1,400-fold enhancement activation. We confirm that HMRef-βGal sensitively...
We have synthesized and evaluated a series of hydroxymethyl rhodamine derivatives found an intriguing difference intramolecular spirocyclization behavior: the acetylated derivative green (Ac-HMRG) exists as closed spirocyclic structure in aqueous solution at physiological pH, whereas HMRG itself takes open nonspirocyclic structure. Ac-HMRG is colorless nonfluorescent, strongly fluorescent. On basis these findings, we developed general design strategy to obtain highly sensitive fluorescence...
We identified a rhodol bearing hydroxymethyl group (HMDER) as suitable scaffold for designing fluorescence probes various hydrolases. HMDER shows strong at physiological pH, but phenolic O-alkylation of results in preference the spirocyclic form, which has weak fluorescence. As proof concept, we utilized this finding to develop new probe β-galactosidase. This favorable characteristics imaging biological samples: it good cellular permeability, and its hydrolysis product is well-retained...
Nano- to micron-size reaction chamber arrays (femtolitre arrays) have facilitated the development of sensitive and quantitative biological assays, such as single-molecule enzymatic digital PCR ELISA. However, versatility femtolitre is limited reactions that occur in aqueous solutions. Here we report an arrayed lipid bilayer system (ALBiC) contains sub-million chambers, each sealed with a stable 4-μm-diameter membrane. When reconstituted limiting amount membrane transporter proteins...
Screening colonoscopy to monitor for early colitis-associated colon cancer (CAC) is difficult due the aberrant mucosal patterns associated with long-standing colitis. The aim of this study was develop a rapid fluorescent detection method use during improving CAC utilising topically applied enzymatically activatable probe (gGlu-HMRG) which fluoresces in presence γ-glutamyltranspeptidase (GGT), an enzyme cancer.Expression GGT cell lines examined fluorescence microscopy and flow cytometry. A...
Abstract Live imaging of exocytosis dynamics is crucial for a precise spatiotemporal understanding secretion phenomena, but current approaches have serious limitations. We designed and synthesized small‐molecular fluorescent probes that were chemically optimized sensing acidic intravesicular pH values, established they can be used to sensitively reliably visualize vesicular following stimulation. This straightforward technique the visualization as well endocytosis/reacidification processes...
Precise tumor diagnosis and evaluation of disease extent are crucial for treatment solid cancers. In order to complement the limited ability unaided human eye discriminate tissue normal tissue, we have developed a series fluorescence probes activatable specifically in cancer tissues. Here, describe design, synthesis, application new probe targeting hexosaminidase (HMRef-βGlcNAc), which is located lysosomes overexpressed several carcinomas, including colorectal cancer. This could sensitively...
Adenosine 5’ triphosphate (ATP) is a ubiquitous extracellular signaling messenger. Here, we describe method for in-vivo imaging of ATP with high spatiotemporal resolution. We prepared comprehensive set cysteine-substitution mutants ATP-binding protein, Bacillus FoF 1 -ATP synthase ε subunit, labeled small-molecule fluorophores at the introduced cysteine residue. Screening revealed that Cy3-labeled glutamine-105 mutant (Q105C-Cy3; designated ATPOS) shows large fluorescence change in presence...
GM2 gangliosidoses, including Tay-Sachs and Sandhoff diseases, are neurodegenerative lysosomal storage diseases that caused by deficiency of β-hexosaminidase A, which comprises an αβ heterodimer. There no effective treatments for these diseases; however, various strategies aimed at restoring A have been explored. Here, we produced a modified human hexosaminidase subunit β (HexB), termed mod2B, composed homodimeric subunits contain amino acid sequences from the α confer ganglioside-degrading...
Abstract Fluorescent sensors are powerful tools for visualizing cellular molecular dynamics. We present a high‐throughput screening system, designated hybrid‐type fluorescence indicator development (HyFInD), to identify optimal position‐specific fluorophore labeling in consisting of combinations ligand‐binding protein mutants with small fluorophores. screened glutamate among hybrid molecules obtained by the reaction four cysteine‐reactive probes set cysteine‐scanning 274 amino acid S1S2...
We found an F-actin–binding small molecule serving as a fluorescent probe and scaffold for functional probes.
Abstract Live imaging of exocytosis dynamics is crucial for a precise spatiotemporal understanding secretion phenomena, but current approaches have serious limitations. We designed and synthesized small‐molecular fluorescent probes that were chemically optimized sensing acidic intravesicular pH values, established they can be used to sensitively reliably visualize vesicular following stimulation. This straightforward technique the visualization as well endocytosis/reacidification processes...
Abstract Microglia are resident immune cells in the central nervous system, showing a regular distribution. Advancing microscopy and image processing techniques have contributed to elucidating microglia’s morphology, dynamics, However, mechanism underlying distribution of microglia remains be elucidated. First, we quantitatively confirmed regularity pattern microglial soma retina. Second, formulated mathematical model that includes factors may influence Next, experimentally quantified...
Adenosine 5'-triphosphate (ATP) works as an extracellular signaling molecule for cells in the brain, such neurons and glia. Cellular communication via release of ATP is involved a range processes required normal brain functions, aberrant associated with disorders. To investigate mechanisms underlying these cellular processes, various techniques have been developed measurement ATP. monitor dynamics high spatiotemporal resolution, we recently hybrid-type optical sensor (ATPOS) that enables