Naganuma, Tatsuro



Faculty of Pharmacy, Department of Pharmacy 代謝生理化学講座 (Shiba-Kyoritsu)


Research Associate/Assistant Professor/Instructor

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Profile Summary 【 Display / hide

  • Varieties of the lipid molecules are involved in the maintenance of skin homeostasis by exerting their characteristic bioactivities or physiological functions. For instance, ceramide species themselves form hydrophobic barrier which is indispensable for skin barrier function, or one of ω3 fatty acid-derived lipid mediator can resolve skin inflammation. Then, to clarify the cause of cutaneous disorders, we should globally understand the whole lipid profiles in disease onset. I’m performing the lipidomics using LC-MS/MS in various models of skin disorders such as atopic dermatitis, psoriasis, and contact dermatitis to unveil the molecular machinery underlying each pathology. Moreover, I’m trying to find new lipid metabolites and their physiological functions which are responsible for the maintenance of skin homeostasis.

Career 【 Display / hide

  • 2016.04

    理化学研究所, 生命医科学研究センター メタボローム研究チーム, 基礎科学特別研究員

  • 2016.08

    理化学研究所, 生命医科学研究センター メタボローム研究チーム, 客員研究員

  • 2016.08

    慶應義塾大学, 薬学部 代謝生理化学講座, 助教

Academic Background 【 Display / hide

  • 2006.04

    Hokkaido University, 薬学部, 薬学科

    University, Graduated

  • 2012.04

    Hokkaido University, 大学院生命科学院, 臨床薬学専攻

    Graduate School, Graduated, Doctoral course

Academic Degrees 【 Display / hide

  • 臨床薬学, Hokkaido University, Coursework, 2016.03

    皮膚神経疾患シェーグレン・ラルソン症候群原因遺伝子 Aldh3a2 のノックアウトマウスを用いた皮膚病態解析

Licenses and Qualifications 【 Display / hide

  • 薬剤師


Research Areas 【 Display / hide

  • Biological pharmacy

Research Keywords 【 Display / hide

  • 脂質,生化学,メタボローム,皮膚,酸化リン脂質


Papers 【 Display / hide

  • Catalytic residues, substrate specificity, and role in carbon starvation of the 2-hydroxy FA dioxygenase Mpol in yeast

    Mon K., Obara T., Seki N., Miyamoto M., Naganuma T., Kitamura T., Kihara A.

    Journal of Lipid Research (Journal of Lipid Research)  61 ( 7 )  2020.07

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  00222275

     View Summary

    © 2020 American Society for Biochemistry and Molecular Biology Inc.. All rights reserved. The yeast protein Mpol belongs to a protein family that is widely conserved in bacteria, fungi, protozoa, and plants, and is the only protein of this family whose function has so far been elucidated. Mpol is an Fe2+-dependent dioxygenase that catalyzes the α-oxidation reaction of 2-hydroxy (2-OH) long-chain FAs produced in the degradation pathway of the long-chain base phytosphingosine. However, several biochemical characteristics of Mpol, such as its catalytic residues, membrane topology, and substrate specificity, remain unclear. Here, we report that yeast Mpo 1 contains two transmembrane domains and that both its N- and C-terminal regions are exposed to the cytosol. Mutational analyses revealed that three histidine residues conserved in the Mpol family are especially important for Mpol activity, suggesting that they may be responsible for the formation of coordinate bonds with Fe2+. We found that, in addition to activity toward 2-OH long-chain FAs, Mpol also exhibits activity toward 2-OH very-long-chain FAs derived from the FA moiety of sphingoids. These results indicate that Mpo 1 is involved in the metabolism of long-chain to very-long-chain 2-OH FAs produced in different pathways. We noted that the growth of mpol A cells is delayed upon carbon deprivation, suggesting that the Mpol-mediated conversion of 2-OH FAs to non-hydroxy FAs is important for utilizing 2-OH FAs as a carbon source under carbon starvation. Our findings help to elucidate the as-yet-unknown functions and activities of other Mpol family members.

  • Homeostatic Function of Dermokine in the Skin Barrier and Inflammation.

    1. Akira Utsunomiya, Takenao Chino, Natsuko Utsunomiya, Vu Huy Luong, Atsushi Tokuriki, Tatsuro Naganuma, Makoto Arita, Kiyoshi Higashi, Koichi Saito, Noriyuki Suzuki, Ayako Ohara, Manabu Sugai, Koji Sugawara, Daisuke Tsuruta, Noritaka Oyama, Minoru Hasegawa

    J Invest Dermatol (Journal of Investigative Dermatology)  140 ( 4 ) 838 - 849.e9 2020

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  0022202X

     View Summary

    © 2019 The Authors Dermokine is a chiefly skin-specific secreted glycoprotein localized in the upper epidermis, and its family consists of three splice variants in mice and five in humans. To investigate the pathophysiological impact of dermokine, we generated mice deficient for two (βγ) or all dermokine isoforms (αβγ). Both variants, especially dermokine αβγ-deficient mice exhibited scale and wrinkle formation resembling ichthyosis accompanied by transepidermal water imbalance at the neonatal stage. Several dermokine αβγ-deficient mice died by postnatal day 21 when reared under low humidity. Moreover, the cornified envelope was vulnerable, and skin barrier lipid ceramides were reduced in the epidermis of dermokine αβγ-deficient mice. cDNA microarray and quantitative reverse transcriptase–PCR assays of the epidermis revealed the upregulation of small proline-rich protein and late cornified envelope family members, as well as antimicrobial peptides in the dermokine αβγ-deficient mice. These barrier gene signatures were similar to that seen in psoriasis, whereas recent studies demonstrated that congenital ichthyosis has gene profiles resembling psoriasis. In line with these findings, adult dermokine αβγ-deficient mice exhibited aggravated phenotypes in psoriasis-like dermatitis models but not in allergic dermatitis models. Dermokine may play a regulatory role in inflammatory dyskeratotic diseases, such as congenital ichthyosis and psoriasis, in the crosstalk between barrier dysfunction and inflammation.

  • Decreased skin barrier lipid acylceramide and differentiation-dependent gene expression in ichthyosis gene Nipal4 knockout mice.

    Honda Y, Kitamura T, Naganuma T, Abe T, Ohno Y, Sassa T, Kihara A.

    J Invest Dermatol (Journal of Investigative Dermatology)  138 ( 4 ) 741 - 749 2018.04

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  0022202X

     View Summary

    © 2017 The Authors NIPAL4 is one of the causative genes for autosomal recessive congenital ichthyosis. However, the role of NIPAL4 in skin barrier formation and the molecular mechanism of ichthyosis pathology caused by NIPAL4 mutations, have not yet been determined. Here, we found that Nipal4-knockout (KO) mice exhibited neonatal lethality due to skin barrier defects. Histological analyses showed several morphological abnormalities in the Nipal4-KO epidermis, including impairment of lipid multilayer structure formation, hyperkeratosis, immature keratohyalin granules, and developed heterochromatin structures. The levels of the skin barrier lipid acylceramide were decreased in Nipal4-KO mice. Expression of genes involved in skin barrier formation normally increases during keratinocyte differentiation, in which chromatin remodeling is involved. However, the induction of Krt1, Lor, Flg, Elovl1, and Dgat2 was impaired in Nipal4-KO mice. NIPAL4 is a putative Mg2+ transporter, and Mg2+ concentration in differentiated keratinocytes of Nipal4-KO mice was indeed lower than that of wild-type mice. Our results suggest that low Mg2+ concentration causes aberration in the proper chromatin remodeling process, which in turn leads to failure of differentiation-dependent gene induction in keratinocytes. Our findings provide insights into Mg2+-dependent regulation of gene expression and skin barrier formation during keratinocyte differentiation.

  • Disruption of the Sjogren-Larsson Syndrome Gene Aldh3a2 in Mice Increases Keratinocyte Growth and Retards Skin Barrier Recovery

    Naganuma Tatsuro, Takagi Shuyu, Kanetake Tsukasa, Kitamura Takuya, Hattori Satoko, Miyakawa Tsuyoshi, Sassa Takayuki, Kihara Akio

    JOURNAL OF BIOLOGICAL CHEMISTRY 291 ( 22 ) 11676 - 11688 2016.05

    Research paper (scientific journal), Accepted,  ISSN  0021-9258

  • Long-chain bases of sphingolipids are transported into cells via the acyl-CoA synthetases

    Narita Tomomi, Naganuma Tatsuro, Sase Yurie, Kihara Akio

    SCIENTIFIC REPORTS 6   1395 - 1401 2016.05

    Research paper (scientific journal), Accepted,  ISSN  2045-2322

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

Reviews, Commentaries, etc. 【 Display / hide

  • 皮膚疾患とリピドミクス


    医学のあゆみ (医歯薬出版)  270 ( 5 ) 409 - 415 2019.08

    Introduction and explanation (scientific journal)

  • 脂肪酸クオリティと炎症・アレルギーの制御


    免疫と炎症 (先端医学社)  25 ( 4 ) 265 - 270 2017.06

    Introduction and explanation (scientific journal)

Presentations 【 Display / hide

  • Aberrant sebaceous lipid metabolism in the early stage of spontaneous dermatitis in Tmem79-deficient mice

    Ari Morimoto, Yoshihiro Ito, Takashi Sasaki, Aiko Shiohama, Hiroshi Kawasaki, Ai Hirabayashi, Mayuko Sato, Kiminori Toyooka, Eiryo Kawakami, Tatsuro Naganuma, Makoto Arita, Haruhiko Koseki, Takeshi Matsui, Masayuki Amagai

    JSID 2020, 2020.06

  • 炎症性皮膚疾患の病態形成過程における脂質代謝変動の包括的メタボローム解析


    第62回 JCBL, 2020.04, Oral Presentation(general)

  • 自然発症皮膚炎モデルマウスであるTmem79欠損マウスは発症早期に脂質代謝異常を示す


    第41回日本炎症・再生医学会, 2020.02

  • ヒト培養ケラチノサイトにおける脂肪酸代謝系の包括的解析


    第92回 日本生化学会大会, 2019.09, Poster (general)

  • アレルギー性接触皮膚炎の病態形成過程における脂肪酸代謝系の包括的解析


    第18回次世代を担う若手ファーマ・バイオフォーラム2019, 2019.09, Oral Presentation(general)

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • 皮膚炎発症過程における脂質代謝変化の網羅的リピドミクス解析


    日本学術振興会, 科学研究費補助金(文部科学省・日本学術振興会), 若手研究, Research grant, Principal Investigator

  • 皮膚炎横断的リピドミクスによる炎症性皮膚疾患の病態解析


    小野医学研究財団, 第27回研究奨励助成, 永沼達郎, Research grant, Principal Investigator

  • 皮膚疾患の発症に関わる脂質代謝系のマルチオミクス解析


    セコム科学技術振興財団, 挑戦的研究助成, Research grant, Principal Investigator

  • 皮膚恒常性に関わる脂質代謝系の包括的理解を目指した網羅的メタボローム解析


    日本学術振興会, Grant-in-Aid for Scientific Research, Research grant, Principal Investigator

  • ω3脂肪酸による皮膚恒常性制御機構の解析


    慶應義塾大学, Keio Gijuku Fukuzawa Memorial Fund for the Advancement of Education and Research

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Courses Taught 【 Display / hide











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Courses Previously Taught 【 Display / hide

  • 実験法概論

    Keio University, 2017, Autumn Semester

  • 代謝生化学

    Keio University, 2017, Spring Semester, Major subject

  • 機能生理学2

    Keio University, 2017, Spring Semester

  • システム生体機能学特論

    Keio University, 2017, Spring Semester

  • 生物系薬学特論II

    Keio University, 2017, Spring Semester

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Memberships in Academic Societies 【 Display / hide

  • 日本生化学会

  • セラミド研究会