Details of a Researcher - Uchino, Haruki

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)

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2023.04

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2026.03

RIKEN IMS, Laboratory for Metabolomics, Postdoctoral Researcher
2026.04

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Present

RIKEN IMS, Laboratory for Metabolomics, Visiting Scientist

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Academic Degrees 【 Display / hide 】

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

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ノンターゲットリピドミクスのデータ取得

内野春希, 有田誠, 実験医学別冊「実験デザインからわかるマルチオミクス研究実践テキスト」 (羊土社), 2025.03
リピドームアトラス構築のための空間リピドミクス解析

内野春希, 有田誠, 医学のあゆみ（医歯薬出版社）, 2024.06
質量分析イメージング法によるリピドームアトラスの創出

内野春希, 有田誠, 医学のあゆみ（医歯薬出版）, 2023.12
脂質クオリティの多様性を解き明かす最先端リピドミクス解析技術

内野春希, 有田誠, 実験医学増刊「マルチオミクス」（羊土社）, 2023.09
リポクオリティの違いを捉えるノンターゲット脂質解析

内野春希, 津川裕司, 有田誠, 医学のあゆみ（医歯薬出版）, 2019.06

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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.
- Access to Document (DOI)
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.
- Access to Document (DOI)
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.
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Combined Targeting Patient-Specific Anti-Apoptotic Molecules and CXCR4-Expressing CAR-T Cells Eliminated High-Inflammation State Leukemia with Poor-Prognostic Mutations

R Nakagawa, Y Isobe, A Itoh-Nakadai, H Uchino, M Liang, A Kaneko, ...

Blood 144, 1453 2024

Lead author, Last author, Corresponding author, Accepted
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

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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−/− and GPSN2+/− mice show abnormal neuronal networks as a result of impaired neuronal polarity determination. Lipidomics of GPSN2−/− 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+/− neurons lose gangliosides in their membranes. Application of C24:0 ceramide, but not C16:0 ceramide or C24:0 phosphatidylcholine, to GPSN2+/− 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.
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