Uchino, Haruki

写真a

Affiliation

Faculty of Pharmacy, Department of Pharmacy ( Shiba-Kyoritsu )

Position

Project Assistant Professor (Non-tenured)/Project Research Associate (Non-tenured)/Project Instructor (Non-tenured)
Page Top ▲

Career 【 Display / hide 】

  • 2023.04
    -
    2026.03

    RIKEN IMS, Laboratory for Metabolomics, Postdoctoral Researcher

  • 2026.04
    -
    Present

    RIKEN IMS, Laboratory for Metabolomics, Visiting Scientist

Page Top ▲

Academic Degrees 【 Display / hide 】

  • Ph.D. (Pharmacy), Keio University, Coursework, 2023.03

Page Top ▲
 

Papers 【 Display / hide 】

  • SMASH Imaging: A Serial Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Strategy for High-Resolution Imaging Facilitates Dual-Polarity and MS2 Spatial Lipidomics on a Single Tissue Section

    Uchino H., Tsugawa H., Arita M.

    Analytical Chemistry 98 ( 13 ) 9540 - 9554 2026.04

    ISSN  00032700

    　View Summary

    Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a key technology in spatial lipidomics that provides high sensitivity and spatial resolution. Because of the ionization preference of lipid classes and the lack of detailed structural information without MS2 data, dual-polarity analyses and the acquisition of MS/MS spectra are essential to improve coverage and annotation accuracy. Multitime MSI analyses of the same tissue section can provide seamless integration of multimodal spatial data. However, the feasibility of performing serial MALDI-MSI for the same pixels with high spatial resolution has not been fully evaluated. Here, we present SMASH imaging for dual-polarity and MS2 spatial lipidomics in a single tissue section. We estimated two characteristic matrix compounds, 2,5-dihydroxyacetophenone and trans-2-[3-(4-tert-butylphenyl)-2-methyl-2-propenylidene]malononitrile, for dual-polarity analyses and defined the feasible number of layers of SMASH imaging via the coefficient of determination (R2). SMASH imaging successfully visualized over 400 lipid species on average with a 30 μm resolution, with annotation criteria S/N ≥ 50, m/z ≤ 10 mDa, and collision cross section ≤ 20 Å2. In four layers of SMASH imaging, the molecular species of 18 lipids were characterized based on MS2 spectra evidence using parallel accumulation-serial fragmentation on a single mouse brain section. Moreover, eight layers of SMASH imaging with a 5 μm spatial resolution annotated 25 lipid species, supported by a spatial correlation metric between multimodal data. Our approach provides multimodal spatial lipidomics to create a lipidome atlas with accurate annotation and high spatial resolution on a single tissue section.

  • The Microbiome Modulates Corneal Wound Healing via the Induction of Cholesterol Sulfotransferase Pathway

    Ogawa M., Isobe Y., Uchino H., Hirayama M., Kato T., Negishi K., Arita M.

    FASEB Journal 40 ( 2 )  2026.01

    ISSN  08926638

    　View Summary

    The ocular surface is in direct contact with the external environment and is susceptible to injury from dust, dryness, or other foreign objects. Once corneal injury occurs, a local inflammatory response is triggered, followed by effective repair of the epithelial layer. In this study, we demonstrated that antibiotic treatment delayed corneal wound healing in mice. LC–MS/MS-based untargeted lipidomics and qPCR analyses revealed that the levels of cholesterol sulfate (CS) and the CS-synthesizing enzyme SULT2B1 were significantly upregulated by antibiotic treatment, and SULT2B1 knockout mice exhibited accelerated corneal wound healing along with increased recruitment of neutrophils and eosinophils. Topical application of CS delayed corneal wound healing. In vitro scratch assays revealed that CS delayed the wound healing of human corneal epithelial cells, potentially by inhibiting the DOCK2-Rac pathway. These results highlight the role of commensal bacteria in controlling corneal wound healing via the cholesterol-sulfotransferase pathway.

  • MS-DIAL 5 multimodal mass spectrometry data mining unveils lipidome complexities

    Takeda H., Matsuzawa Y., Takeuchi M., Takahashi M., Nishida K., Harayama T., Todoroki Y., Shimizu K., Sakamoto N., Oka T., Maekawa M., Chung M.H., Kurizaki Y., Kiuchi S., Tokiyoshi K., Buyantogtokh B., Kurata M., Kvasnička A., Takeda U., Uchino H., Hasegawa M., Miyamoto J., Tanabe K., Takeda S., Mori T., Kumakubo R., Tanaka T., Yoshino T., Okamoto M., Takahashi H., Arita M., Tsugawa H.

    Nature Communications 15 ( 1 )  2024.12

    　View Summary

    Lipidomics and metabolomics communities comprise various informatics tools; however, software programs handling multimodal mass spectrometry (MS) data with structural annotations guided by the Lipidomics Standards Initiative are limited. Here, we provide MS-DIAL 5 for in-depth lipidome structural elucidation through electron-activated dissociation (EAD)-based tandem MS and determining their molecular localization through MS imaging (MSI) data using a species/tissue-specific lipidome database containing the predicted collision-cross section values. With the optimized EAD settings using 14 eV kinetic energy, the program correctly delineated lipid structures for 96.4% of authentic standards, among which 78.0% had the sn-, OH-, and/or C = C positions correctly assigned at concentrations exceeding 1 μM. We showcased our workflow by annotating the sn- and double-bond positions of eye-specific phosphatidylcholines containing very-long-chain polyunsaturated fatty acids (VLC-PUFAs), characterized as PC n-3-VLC-PUFA/FA. Using MSI data from the eye and n-3-VLC-PUFA-supplemented HeLa cells, we identified glycerol 3-phosphate acyltransferase as an enzyme candidate responsible for incorporating n-3 VLC-PUFAs into the sn1 position of phospholipids in mammalian cells, which was confirmed using EAD-MS/MS and recombinant proteins in a cell-free system. Therefore, the MS-DIAL 5 environment, combined with optimized MS data acquisition methods, facilitates a better understanding of lipid structures and their localization, offering insights into lipid biology.

  • Very-long-chain fatty acids are crucial to neuronal polarity by providing sphingolipids to lipid rafts

    Honda A., Nozumi M., Ito Y., Natsume R., Kawasaki A., Nakatsu F., Abe M., Uchino H., Matsushita N., Ikeda K., Arita M., Sakimura K., Igarashi M.

    Cell Reports 42 ( 10 )  2023.10

    　View Summary

    Fatty acids have long been considered essential to brain development; however, the involvement of their synthesis in nervous system formation is unclear. We generate mice with knockout of GPSN2, an enzyme for synthesis of very-long-chain fatty acids (VLCFAs) and investigate the effects. Both GPSN2<sup>−/−</sup> and GPSN2<sup>+/−</sup> mice show abnormal neuronal networks as a result of impaired neuronal polarity determination. Lipidomics of GPSN2<sup>−/−</sup> embryos reveal that ceramide synthesis is specifically inhibited depending on FA length; namely, VLCFA-containing ceramide is reduced. We demonstrate that lipid rafts are highly enriched in growth cones and that GPSN2<sup>+/−</sup> neurons lose gangliosides in their membranes. Application of C24:0 ceramide, but not C16:0 ceramide or C24:0 phosphatidylcholine, to GPSN2<sup>+/−</sup> neurons rescues both neuronal polarity determination and lipid-raft density in the growth cone. Taken together, our results indicate that VLCFA synthesis contributes to physiological neuronal development in brain network formation, in particular neuronal polarity determination through the formation of lipid rafts.

  • Long chain acyl-CoA synthetase 6 facilitates the local distribution of di-docosahexaenoic acid- and ultra-long-chain-PUFA-containing phospholipids in the retina to support normal visual function in mice

    Kuroha S., Katada Y., Isobe Y., Uchino H., Shishikura K., Nirasawa T., Tsubota K., Negishi K., Kurihara T., Arita M.

    FASEB Journal 37 ( 9 )  2023.09

    ISSN  08926638

    　View Summary

    Docosahexaenoic acid (DHA) and ultra-long-chain polyunsaturated fatty acids (ULC–PUFAs) are uniquely enriched in membrane phospholipids of retinal photoreceptors. Several studies have shown that di-DHA- and ULC–PUFA-containing phospholipids in photoreceptors have an important role in maintaining normal visual function; however, the molecular mechanisms underlying the synthesis and enrichment of these unique lipids in the retina, and their specific roles in retinal function remain unclear. Long-chain acyl-coenzyme A (CoA) synthetase 6 (ACSL6) preferentially converts DHA into DHA–CoA, which is a substrate during DHA-containing lipid biosynthesis. Here, we report that Acsl6 mRNA is expressed in the inner segment of photoreceptor cells and the retinal pigment epithelial cells, and genetic deletion of ACSL6 resulted in the selective depletion of di-DHA– and ULC–PUFA-containing phospholipids, but not mono-DHA-containing phospholipids in the retina. MALDI mass spectrometry imaging (MALDI–MSI) revealed the selective distribution of di-DHA– and ULC–PUFA-containing phospholipids in the photoreceptor outer segment (OS). Electroretinogram of Acsl6<sup>−/−</sup> mice exhibited photoreceptor cell-derived visual impairment, whereas the expression levels and localization of opsin proteins were unchanged. Acsl6<sup>−/−</sup> mice exhibited an age-dependent progressive decrease of the thickness of the outer nuclear layers, whereas the inner nuclear layers and OSs were normal. These results demonstrate that ACSL6 facilitates the local enrichment of di-DHA– and ULC–PUFA-containing phospholipids in the retina, which supports normal visual function and retinal homeostasis.

display all >>

Page Top ▲

Papers, etc., Registered in KOARA 【 Display / hide 】

Page Top ▲