研究者基本情報

• 博士（臨床薬学）, 北海道大学, 2016年03月

• https://researchmap.jp/NGNMT

• 60779619

• https://orcid.org/0000-0002-8653-5553

• 201601020565206600

• 脂質，脂肪酸，スフィンゴ脂質，生化学，リピドミクス

• ライフサイエンス, 薬系衛生、生物化学

• 学士課程, 薬学部
• 修士課程, 生命科学院
• 博士課程, 生命科学院

研究活動情報

• 2011年10月, 第10回次世代若手を担うバイオ・ファーマフォーラム, 優秀発表賞
  哺乳類極長鎖脂肪酸伸長酵素ELOVLの生化学的解析
  永沼達郎;佐藤佑一朗;佐々貴之;大野祐介;木原章雄
• 2011年09月, 日本生化学会, 鈴木紘一メモリアル賞
  極長鎖脂肪酸伸長に関わる縮合酵素ELOVLの生化学的解析
  永沼達郎;佐藤佑一朗;佐々貴之;大野祐介;木原章雄
• 2011年05月, 日本薬学会北海道支部, 学生優秀発表賞
  極長鎖脂肪酸伸長酵素ELOVLの生化学的解析
  永沼達郎;佐藤佑一朗;佐々貴之;大野祐介;木原章雄

• Acid ceramidase ASAH1 is a key regulator of epidermal ceramide levels and composition
  Wakana Nobumoto; Tatsuro Naganuma; Nana Nozaka; Yusuke Ohno; Koki Nojiri; Akio Kihara
  Journal of Biological Chemistry, 2026年03月
  研究論文（学術雑誌）
• Fatty acyl-CoA reductase FAR1 is essential for the testicular seminolipid synthesis required for spermatogenesis and male fertility.
  Ayano Tamazawa; Tatsuro Naganuma; Kento Otsuka; Tenga Takahashi; Takayuki Sassa; Akio Kihara
  The Journal of biological chemistry, 301, 6, 108538, 108538, 2025年06月, ［国際誌］
  英語, 研究論文（学術雑誌）, Seminolipids are testis-specific ether glycolipids that are important for spermatogenesis. The fatty alcohol (ether-linked alkyl moiety) in ether lipids is generated from an acyl-CoA by fatty acyl-CoA reductase (FAR). To date, the diversity of the alkyl and acyl moieties in seminolipids, the specific stage of spermatogenesis during which seminolipids are produced, and the FAR isozyme (FAR1 or FAR2) involved in the synthesis of the alkyl moieties have remained largely unclear. Here, we demonstrated that Far1 is expressed in the mouse testis via quantitative RT-PCR analysis, whereas Far2 was barely detectable. In situ hybridization and quantitative RT-PCR analysis of spermatogenic cells separated via FACS revealed that Far1 is expressed in spermatogonia, spermatocytes, and spermatids. We generated Far1 KO mice and found that male Far1 KO mice were infertile. In these mice, sperms were absent in the epididymides and the testes were small, with multinucleated cells and vacuoles in the seminiferous tubules. LC-MS/MS analysis showed that the vast majority of seminolipids (>90%) in WT mouse testes contained C16:0 in both the alkyl and the acyl moieties. Seminolipids were present in all subclasses of spermatogenic cells in WT mice, but they were absent in Far1 KO mice. Instead, the production of nonether, diacyl-type sulfogalactosyl lipids (sulfogalactosyl diacylglycerols) was induced in Far1 KO mice. In conclusion, the alkyl and acyl moieties of seminolipids in the testis are low in diversity, and Far1 is essential for seminolipid synthesis and spermatogenesis.
• Celecoxib prevents malignant progression of smoking-induced lung tumors via suppression of the COX-2/PGE2 signaling pathway in mice.
  Kaori Sakurai; Shotaro Chubachi; Jun Miyata; Junko Hamamoto; Tatsuro Naganuma; Takashi Shimada; Shiro Otake; Shingo Nakayama; Hidehiro Irie; Akihiro Tsutsumi; Naofumi Kameyama; Ahmed E Hegab; Masayuki Shimoda; Hideki Terai; Hiroyuki Yasuda; Yae Kanai; Makoto Arita; Koichi Fukunaga
  Frontiers in immunology, 16, 1557790, 1557790, 2025年, ［国際誌］
  英語, 研究論文（学術雑誌）, INTRODUCTION: Lung cancer is characterized by a poor prognosis and is a significant comorbidity of chronic obstructive pulmonary disease (COPD). Therefore, effective chemopreventive agents are warranted. We evaluated the effects of the cyclooxygenase-2 (COX-2) inhibitor celecoxib on the prevention of lung-carcinoma development using an intermittent smoking-induced lung-carcinoma mouse model. Additionally, we explored COX-2's role in lipid metabolism. METHODS: Male A/J mice were exposed to sham air or mainstream cigarette smoke for 20 weeks. Vehicle or celecoxib was administered via intragastric feeding once daily. Lung tissues were analyzed for tumor nodules and emphysema; the bronchoalveolar lavage fluid was collected for cell counting. COX-2 expression was measured using real-time polymerase chain reaction and western blotting; lipidomic analysis was conducted using liquid chromatography-tandem mass spectrometry. Cell proliferation and colony-forming assays were performed on LA-4 cells to assess the effects of prostaglandins and COX-2 inhibitors. RESULTS: Intermittent smoking exposure increased lung adenomas, adenocarcinomas, and COX-2 expression. Lung adenomas were characterized by abundant COX-2-positive cells. Celecoxib reduced intermittent smoking-induced inflammation, emphysema, and cell counts in the bronchoalveolar lavage fluid and decreased the incidence of lung adenocarcinomas, whereas the total number of observed lung tumors was unchanged. Celecoxib markedly suppressed single-smoke-induced prostaglandin E2 (PGE2) production in the airway. PGE2 increased LA-4 cell viability via the EP4 receptor and promoted colony formation. DISCUSSION: Celecoxib effectively inhibited lung-carcinoma development, inflammation, and emphysema, demonstrating the potential for chemoprevention in smokers and patients with COPD. Further studies on EP4 inhibitors for the prevention of emphysema and lung cancer are warranted.
• Role of 2-hydroxy acyl-CoA lyase HACL2 in odd-chain fatty acid production via α-oxidation in vivo.
  Keisuke Mori; Tatsuro Naganuma; Akio Kihara
  Molecular biology of the cell, 34, 9, ar85, 2023年08月01日, ［国際誌］
  英語, 研究論文（学術雑誌）, Although most fatty acids (FAs) are even chain, certain tissues, including brain, contain relatively large quantities of odd-chain FAs in their sphingolipids. One of the pathways producing odd-chain FAs is the α-oxidation of 2-hydroxy (2-OH) FAs, where 2-OH acyl-CoA lyases (HACL1 and HACL2) catalyze the key cleavage reaction. However, the contribution of each HACL to odd-chain FA production in vivo remains unknown. Here, we found that HACL2 and HACL1 play major roles in the α-oxidation of 2-OH FAs (especially very-long-chain types) and 3-methyl FAs (other α-oxidation substrates), respectively, using ectopic expression systems of human HACL2 and HACL1 in yeast and analyzing Hacl1 and/or Hacl2 knockout (KO) CHO-K1 cells. We then generated Hacl2 KO mice and measured the quantities of odd-chain and 2-OH lipids (free FAs and sphingolipids [ceramides, sphingomyelins, and monohexosylceramides]) in 17 tissues. We observed fewer odd-chain lipids and more 2-OH lipids in many tissues of Hacl2 KO mice than in wild-type mice, and of these differences the reductions were most prominent for odd-chain monohexosylceramides in the brain and ceramides in the stomach. These results indicate that HACL2-involved α-oxidation of 2-OH FAs is mainly responsible for odd-chain FA production in the brain and stomach.
• Bifunctional DEGS2 has higher hydroxylase activity toward substrates with very-long-chain fatty acids in the production of phytosphingosine ceramides.
  Ai Ota; Hiroya Morita; Tatsuro Naganuma; Masatoshi Miyamoto; Keisuke Jojima; Koki Nojiri; Junko Matsuda; Akio Kihara
  The Journal of biological chemistry, 299, 4, 104603, 104603, 2023年04月, ［国際誌］
  英語, 研究論文（学術雑誌）, Phytosphingosine (PHS) is a sphingolipid component present mainly in epithelial tissues, including the epidermis and those lining the digestive tract. DEGS2 is a bifunctional enzyme that produces ceramides (CERs) containing PHS (PHS-CERs) via hydroxylation and sphingosine-CERs via desaturation, using dihydrosphingosine-CERs as substrates. Until now, the role of DEGS2 in permeability barrier functioning, its contribution to PHS-CER production, and the mechanism that differentiates between these two activities have been unknown. Here, we analyzed the barrier functioning of the epidermis, esophagus, and anterior stomach of Degs2 KO mice and found that there were no differences between Degs2 KO and WT mice, indicating normal permeability barriers in the KO mice. In the epidermis, esophagus, and anterior stomach of Degs2 KO mice, PHS-CER levels were greatly reduced relative to WT mice, but PHS-CERs were still present. We obtained similar results for DEGS2 KO human keratinocytes. These results indicate that although DEGS2 plays a major role in PHS-CER production, another synthesis pathway exists as well. Next, we examined the fatty acid (FA) composition of PHS-CERs in various mouse tissues and found that PHS-CER species containing very-long-chain FAs (≥C21) were more abundant than those containing long-chain FAs (C11-C20). A cell-based assay system revealed that the desaturase and hydroxylase activities of DEGS2 toward substrates with different FA chain lengths differed and that its hydroxylase activity was higher toward substrates containing very-long-chain FAs. Collectively, our findings contribute to the elucidation of the molecular mechanism of PHS-CER production.
• Dysregulated ceramide metabolism in mouse progressive dermatitis resulting from constitutive activation of Jak1.
  Yudai Iino; Tatsuro Naganuma; Makoto Arita
  Journal of lipid research, 64, 2, 100329, 100329, 2023年02月, ［国際誌］
  英語, 研究論文（学術雑誌）, Coordinated lipid metabolism contributes to maintaining skin homeostasis by regulating skin barrier formation, immune reactions, thermogenesis, and perception. Several reports have documented the changes in lipid composition in dermatitis, including in atopic dermatitis (AD); however, the specific mechanism by which these lipid profiles are altered during AD pathogenesis remains unknown. Here, we performed untargeted and targeted lipidomic analyses of an AD-like dermatitis model resulting from constitutive activation of Janus kinase 1 (Spade mice) to capture the comprehensive lipidome profile during dermatitis onset and progression. We successfully annotated over 700 skin lipids, including glycerophospholipids, ceramides, neutral lipids, and fatty acids, many of which were found to be present at significantly changed levels after dermatitis onset, as determined by the pruritus and erythema. Among them, we found the levels of ceramides composed of nonhydroxy fatty acid and dihydrosphingosine containing very long-chain (C22 or more) fatty acids were significantly downregulated before AD onset. Furthermore, in vitro enzyme assays using the skin of Spade mice demonstrated the enhancement of ceramide desaturation. Finally, we revealed topical application of ceramides composed of nonhydroxy fatty acid and dihydrosphingosine before AD onset effectively ameliorated the progression of AD symptoms in Spade mice. Our results suggest that the disruption in epidermal ceramide composition is caused by boosting ceramide desaturation in the initiation phase of AD, which regulates AD pathogenesis.
• Microbiota-Independent Spontaneous Dermatitis Associated With Increased Sebaceous Lipid Production in Tmem79-Deficient Mice.
  Ari Morimoto; Keitaro Fukuda; Yoshihiro Ito; Umi Tahara; Takashi Sasaki; Aiko Shiohama; Hiroshi Kawasaki; Eiryo Kawakami; Tatsuro Naganuma; Makoto Arita; Hiroyuki Sasaki; Haruhiko Koseki; Takeshi Matsui; Masayuki Amagai
  The Journal of investigative dermatology, 2022年06月22日, ［国際誌］
  英語, 研究論文（学術雑誌）, TMEM79 is a predisposing gene for atopic dermatitis (AD). Tmem79-deficient mice develop spontaneous dermatitis in a biphasic pattern. The 1st-phase dermatitis is unique, as it occurs independent of microbiota status, whereas the 2nd-phase dermatitis is microbiota-dependent. In this study, we sought to identify key factors mediating the development of 1st-phase dermatitis. Structural analysis showed that sebaceous gland hyperplasia started from 1st-phase dermatitis. Longitudinal RNA-sequencing analysis revealed significant activation of fatty acid lipid-metabolism pathways in 1st-phase dermatitis, whereas Th17-based immune response genes were highly expressed in 2nd-phase dermatitis. Quantitative reverse transcription-polymerase chain reaction analysis revealed that genes involved in fatty acid elongation and sebocyte differentiation were upregulated in 1st-phase dermatitis. The results of thin-layer chromatography supported these findings with an increased abundance of wax esters, cholesterol esters, and fatty alcohols in hair lipids. Further gas chromatography-tandem mass spectrometry analysis showed an increase in total fatty acid production, including that of elongated C20-24 saturated and C18-24 mono-unsaturated fatty acids. Collectively, these results suggest that aberrant production of sebaceous long-chain fatty acids is associated with microbiota-independent dermatitis. Further investigation of Tmem79-deficient mice may clarify the role of certain fatty acids in dermatitis.
• Polyunsaturated Fatty Acid-Derived Lipid Mediators That Regulate Epithelial Homeostasis.
  Tatsuro Naganuma; Nodoka Fujinami; Makoto Arita
  Biological & pharmaceutical bulletin, 45, 8, 998, 1007, 2022年, ［国内誌］
  英語, 研究論文（学術雑誌）, Epithelial tissues are mainly composed of epithelial cells, covering both internal and external surfaces of our body. To maintain epithelial homeostasis, cellular functions, such as proliferation, migration, and differentiation, are flexibly regulated in response to changes in the cellular status, thereby contributing to barrier formation, immune reaction, and wound closure. Polyunsaturated fatty acids (PUFAs) are precursors of various lipid mediators that maintain tissue homeostasis by exerting characteristic bioactivities. This review aimed to summarize the role of PUFA-derived lipid mediators in epithelial cell functions, mainly focusing on the epidermis, cornea, and intestinal epithelium.
• 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, 61, 7, 1104, 1114, Journal of Lipid Research, 2020年07月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, © 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.
  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
  The Journal of investigative dermatology, 140, 4, 838, 849.e9, Journal of Investigative Dermatology, 2019年10月25日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
  Yuichi Honda; Takuya Kitamura; Tatsuro Naganuma; Takaya Abe; Yusuke Ohno; Takayuki Sassa; Akio Kihara
  The Journal of investigative dermatology, 138, 4, 741, 749, Journal of Investigative Dermatology, 2018年04月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, 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.
• 脂肪酸クオリティと炎症・アレルギーの制御
  永沼達郎; 有田誠
  免疫と炎症, 25, 4, 265, 270, 先端医学社, 2017年06月, ［招待有り］
  日本語
• Disruption of the Sjögren-Larsson Syndrome Gene Aldh3a2 in Mice Increases Keratinocyte Growth and Retards Skin Barrier Recovery.
  Tatsuro Naganuma; Shuyu Takagi; Tsukasa Kanetake; Takuya Kitamura; Satoko Hattori; Tsuyoshi Miyakawa; Takayuki Sassa; Akio Kihara
  The Journal of biological chemistry, 291, 22, 11676, 88, 2016年05月27日, ［国際誌］
  英語, 研究論文（学術雑誌）, The fatty aldehyde dehydrogenase (FALDH) ALDH3A2 is the causative gene of Sjögren Larsson syndrome (SLS). To date, the molecular mechanism underlying the symptoms characterizing SLS has been poorly understood. Using Aldh3a2(-/-) mice, we found here that Aldh3a2 was the major FALDH active in undifferentiated keratinocytes. Long-chain base metabolism was greatly impaired in Aldh3a2(-/-) keratinocytes. Phenotypically, the intercellular spaces were widened in the basal layer of the Aldh3a2(-/-) epidermis due to hyperproliferation of keratinocytes. Furthermore, oxidative stress-induced genes were up-regulated in Aldh3a2(-/-) keratinocytes. Upon keratinocyte differentiation, the activity of another FALDH, Aldh3b2, surpassed that of Aldh3a2 As a result, Aldh3a2(-/-) mice were indistinguishable from wild-type mice in terms of their whole epidermis FALDH activity, and their skin barrier function was uncompromised under normal conditions. However, perturbation of the stratum corneum caused increased transepidermal water loss and delayed barrier recovery in Aldh3a2(-/-) mice. In conclusion, Aldh3a2(-/-) mice replicated some aspects of SLS symptoms, especially at the basal layer of the epidermis. Our results suggest that hyperproliferation of keratinocytes via oxidative stress responses may partly contribute to the ichthyosis symptoms of SLS.
• Long-chain bases of sphingolipids are transported into cells via the acyl-CoA synthetases.
  Tomomi Narita; Tatsuro Naganuma; Yurie Sase; Akio Kihara
  Scientific reports, 6, 25469, 25469, 2016年05月03日, ［国際誌］
  英語, 研究論文（学術雑誌）, Transport of dietary lipids into small-intestinal epithelial cells is pathologically and nutritionally important. However, lipid uptake remains an almost unexplored research area. Although we know that long-chain bases (LCBs), constituents of sphingolipids, can enter into cells efficiently, the molecular mechanism of LCB uptake is completely unclear. Here, we found that the yeast acyl-CoA synthetases (ACSs) Faa1 and Faa4 are redundantly involved in LCB uptake. In addition to fatty acid-activating activity, transporter activity toward long-chain fatty acids (LCFAs) has been suggested for ACSs. Both LCB and LCFA transports were largely impaired in faa1Δ faa4Δ cells. Furthermore, LCB and LCFA uptakes were mutually competitive. However, the energy dependency was different for their transports. Sodium azide/2-deoxy-D-glucose treatment inhibited import of LCFA but not that of LCB. Furthermore, the ATP-AMP motif mutation FAA1 S271A largely impaired the metabolic activity and LCFA uptake, while leaving LCB import unaffected. These results indicate that only LCFA transport requires ATP. Since ACSs do not metabolize LCBs as substrates, Faa1 and Faa4 are likely directly involved in LCB transport. Furthermore, we revealed that ACSs are also involved in LCB transport in mammalian cells. Thus, our findings provide strong support for the hypothesis that ACSs directly transport LCFAs.
• Corrigendum: Identification of the phytosphingosine metabolic pathway leading to odd-numbered fatty acids.
  Kondo N; Ohno Y; Yamagata M; Obara T; Seki N; Kitamura T; Naganuma T; Kihara A
  Nature communications, 2015年04月
  研究論文（学術雑誌）
• Mouse aldehyde dehydrogenase ALDH3B2 is localized to lipid droplets via two C-terminal tryptophan residues and lipid modification.
  Takuya Kitamura; Shuyu Takagi; Tatsuro Naganuma; Akio Kihara
  The Biochemical journal, 465, 1, 79, 87, 2015年01月01日, ［国際誌］
  英語, 研究論文（学術雑誌）, Aldehyde dehydrogenases (ALDHs) catalyse the conversion of toxic aldehydes into non-toxic carboxylic acids. Of the 21 ALDHs in mice, it is the ALDH3 family members (ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2 and ALDH3B3) that are responsible for the removal of lipid-derived aldehydes. However, ALDH3B2 and ALDH3B3 have yet to be characterized. In the present study, we examined the enzyme activity, tissue distribution and subcellular localization of ALDH3B2 and ALDH3B3. Both were found to exhibit broad substrate preferences from medium- to long-chain aldehydes, resembling ALDH3A2 and ALDH3B1. Although ALDH3B2 and ALDH3B3 share extremely high sequence similarity, their localizations differ, with ALDH3B2 found in lipid droplets and ALDH3B3 localized to the plasma membrane. Both were modified by prenylation at their C-termini; this modification greatly influenced their membrane localization and enzymatic activity towards hexadecanal. We found that their C-terminal regions, particularly the two tryptophan residues (Trp462 and Trp469) of ALDH3B2 and the two arginine residues (Arg462 and Arg463) of ALDH3B3, were important for the determination of their specific localization. Abnormal quantity and perhaps quality of lipid droplets are implicated in several metabolic diseases. We speculate that ALDH3B2 acts to remove lipid-derived aldehydes in lipid droplets generated via oxidative stress as a quality control mechanism.
• Identification of the phytosphingosine metabolic pathway leading to odd-numbered fatty acids.
  Natsuki Kondo; Yusuke Ohno; Maki Yamagata; Takashi Obara; Naoya Seki; Takuya Kitamura; Tatsuro Naganuma; Akio Kihara
  Nature communications, 5, 5338, 5338, 2014年10月27日, ［国際誌］
  英語, 研究論文（学術雑誌）, The long-chain base phytosphingosine is a component of sphingolipids and exists in yeast, plants and some mammalian tissues. Phytosphingosine is unique in that it possesses an additional hydroxyl group compared with other long-chain bases. However, its metabolism is unknown. Here we show that phytosphingosine is metabolized to odd-numbered fatty acids and is incorporated into glycerophospholipids both in yeast and mammalian cells. Disruption of the yeast gene encoding long-chain base 1-phosphate lyase, which catalyzes the committed step in the metabolism of phytosphingosine to glycerophospholipids, causes an ~40% reduction in the level of phosphatidylcholines that contain a C15 fatty acid. We also find that 2-hydroxypalmitic acid is an intermediate of the phytosphingosine metabolic pathway. Furthermore, we show that the yeast MPO1 gene, whose product belongs to a large, conserved protein family of unknown function, is involved in phytosphingosine metabolism. Our findings provide insights into fatty acid diversity and identify a pathway by which hydroxyl group-containing lipids are metabolized.
• Two modes of regulation of the fatty acid elongase ELOVL6 by the 3-ketoacyl-CoA reductase KAR in the fatty acid elongation cycle.
  Tatsuro Naganuma; Akio Kihara
  PloS one, 9, 7, e101823, 87, 2014年, ［国際誌］
  英語, 研究論文（学術雑誌）, Fatty acids (FAs) are diverse molecules, and such diversity is important for lipids to exert their functions under several environmental conditions. FA elongation occurs at the endoplasmic reticulum and produces a variety of FA species; the FA elongation cycle consists of four distinct enzyme reactions. For this cycle to be driven efficiently, there must exist coordinated regulation of protein components of the FA elongation machinery. However, such regulation is poorly understood. In the present study, we performed biochemical analyses using the FA elongase ELOVL6 and the 3-ketoacyl-CoA reductase KAR, which catalyze the first and second steps of the FA elongation cycle, respectively. In vitro FA elongation assays using membrane fractions demonstrated that ELOVL6 activity was enhanced ∼10-fold in the presence of NADPH, although ELOVL6 itself did not require NADPH for its catalysis. On the other hand, KAR does use NADPH as a reductant in its enzyme reaction. Activity of purified ELOVL6 was enhanced by ∼3-fold in the presence of KAR. This effect was KAR enzyme activity-independent, since it was observed in the absence of NADPH and in the KAR mutant. However, ELOVL6 enzyme activity was further enhanced in a KAR enzyme activity-dependent manner. Therefore, KAR regulates ELOVL6 via two modes. In the first mode, KAR may induce conformational changes in ELOVL6 to become structure that can undergo catalysis. In the second mode, conversion of 3-ketoacyl-CoA to 3-hydroxyacyl-CoA by KAR may facilitate release of the product from the presumed ELOVL6-KAR complex.
• Substrate specificity, plasma membrane localization, and lipid modification of the aldehyde dehydrogenase ALDH3B1.
  Takuya Kitamura; Tatsuro Naganuma; Kensuke Abe; Kanae Nakahara; Yusuke Ohno; Akio Kihara
  Biochimica et biophysica acta, 1831, 8, 1395, 401, 2013年08月, ［国際誌］
  英語, 研究論文（学術雑誌）, The accumulation of reactive aldehydes is implicated in the development of several disorders. Aldehyde dehydrogenases (ALDHs) detoxify aldehydes by oxidizing them to the corresponding carboxylic acids. Among the 19 human ALDHs, ALDH3A2 is the only known ALDH that catalyzes the oxidation of long-chain fatty aldehydes including C16 aldehydes (hexadecanal and trans-2-hexadecenal) generated through sphingolipid metabolism. In the present study, we have identified that ALDH3B1 is also active in vitro toward C16 aldehydes and demonstrated that overexpression of ALDH3B1 restores the sphingolipid metabolism in the ALDH3A2-deficient cells. In addition, we have determined that ALDH3B1 is localized in the plasma membrane through its C-terminal dual lipidation (palmitoylation and prenylation) and shown that the prenylation is required particularly for the activity toward hexadecanal. Since knockdown of ALDH3B1 does not cause further impairment of the sphingolipid metabolism in the ALDH3A2-deficient cells, the likely physiological function of ALDH3B1 is to oxidize lipid-derived aldehydes generated in the plasma membrane and not to be involved in the sphingolipid metabolism in the endoplasmic reticulum.
• Identification of residues important for the catalysis, structure maintenance, and substrate specificity of yeast 3-hydroxyacyl-CoA dehydratase Phs1.
  Tomoyo Yazawa; Tatsuro Naganuma; Maki Yamagata; Akio Kihara
  FEBS letters, 587, 6, 804, 9, 2013年03月18日, ［国際誌］
  英語, 研究論文（学術雑誌）, Yeast Phs1 is a 3-hydroxyacyl-CoA dehydratase involved in very long-chain fatty acid elongation. In the present study, we biochemically characterized Phs1 mutants with Ala-substitution at each of seven highly conserved amino-acid residues. All mutants exhibited reduced Phs1 activity. The E60A, Q79A, and R141A mutants were sensitive to digitonin, indicative of their reduced structural integrity. The fatty acid elongation cycle was greatly inhibited in the R83A, R141A, and G152A mutant membranes. The enzyme kinetics study implicated the direct involvement of the Arg83 and Gly152 residues in the catalytic process. The E60A mutation was found to affect the substrate specificity.
• The Sjögren-Larsson syndrome gene encodes a hexadecenal dehydrogenase of the sphingosine 1-phosphate degradation pathway.
  Kanae Nakahara; Aya Ohkuni; Takuya Kitamura; Kensuke Abe; Tatsuro Naganuma; Yusuke Ohno; Raphael A Zoeller; Akio Kihara
  Molecular cell, 46, 4, 461, 71, 2012年05月25日, ［国際誌］
  英語, 研究論文（学術雑誌）, Sphingosine 1-phosphate (S1P) functions not only as a bioactive lipid molecule, but also as an important intermediate of the sole sphingolipid-to-glycerolipid metabolic pathway. However, the precise reactions and the enzymes involved in this pathway remain unresolved. We report here that yeast HFD1 and the Sjögren-Larsson syndrome (SLS)-causative mammalian gene ALDH3A2 are responsible for conversion of the S1P degradation product hexadecenal to hexadecenoic acid. The absence of ALDH3A2 in CHO-K1 mutant cells caused abnormal metabolism of S1P/hexadecenal to ether-linked glycerolipids. Moreover, we demonstrate that yeast Faa1 and Faa4 and mammalian ACSL family members are acyl-CoA synthetases involved in the sphingolipid-to-glycerolipid metabolic pathway and that hexadecenoic acid accumulates in Δfaa1 Δfaa4 mutant cells. These results unveil the entire S1P metabolic pathway: S1P is metabolized to glycerolipids via hexadecenal, hexadecenoic acid, hexadecenoyl-CoA, and palmitoyl-CoA. From our results we propose a possibility that accumulation of the S1P metabolite hexadecenal contributes to the pathogenesis of SLS.
• Biochemical characterization of the very long-chain fatty acid elongase ELOVL7.
  Tatsuro Naganuma; Yuichiro Sato; Takayuki Sassa; Yusuke Ohno; Akio Kihara
  FEBS letters, 585, 20, 3337, 41, 2011年10月20日, ［国際誌］
  英語, 研究論文（学術雑誌）, Very long-chain fatty acids (VLCFAs) have a variety of physiological functions and are related to numerous disorders. The key step of VLCFA elongation is catalyzed by members of the elongase family, ELOVLs. Mammals have seven ELOVLs (ELOVL1-7), yet none of them has been purified and analyzed. In the presented study we purified ELOVL7 and measured its activity by reconstituting it into proteoliposomes. Purified ELOVL7 exhibited high activity toward acyl-CoAs with C18 carbon chain length. The calculated K(m) values toward C18:3(n-3)-CoA and malonyl-CoA were both in the μM range. We also found that progression of the VLCFA cycle enhances ELOVL7 activity.
• Hetero-oligomeric interactions of an ELOVL4 mutant protein: implications in the molecular mechanism of Stargardt-3 macular dystrophy.
  Ayaka Okuda; Tatsuro Naganuma; Yusuke Ohno; Kensuke Abe; Maki Yamagata; Yasuyuki Igarashi; Akio Kihara
  Molecular vision, 16, 260-62, 2438, 45, 2010年11月18日, ［国際誌］
  英語, 研究論文（学術雑誌）, PURPOSE: Stargardt disease 3 (STGD3) is a juvenile macular dystrophy caused by mutations in the elongase of very long-chain fatty acids-like 4 (ELOVL4) gene, which encodes an elongase involved in the production of extremely long-chain fatty acids. The STGD3-related mutations cause production of C-terminally truncated proteins (ELOVL4ΔC). STGD3 is transmitted in an autosomal dominant manner. To date, molecular mechanisms of this pathology have been proposed based solely on the interaction between wild-type ELOVL4 and ELOVL4ΔC. However, analyses of Elovl4ΔC knockin mice revealed reduced levels of not only ELOVL4 substrates, but also of fatty acids with a broad spectrum of chain lengths. Therefore, we investigated the molecular mechanisms responsible for ELOVL4ΔC affecting the entire very long-chain fatty acid (VLCFA) elongation pathway. METHODS: The ELOVL4ΔC protein was expressed in HEK 293T cells, and its effect on elongase activities toward several acyl-CoAs were examined. We also investigated the homo- and hetero-oligomerization of ELOVL4ΔC with other elongases (ELOVL1-7) or with other enzymes involved in VLCFA elongation using coimmunoprecipitation experiments. RESULTS: We found that ELOVL4ΔC forms a homo-oligomer more strongly than wild-type ELOVL4. ELOVL4ΔC also interacts strongly with other elongases, although similar interactions for wild-type ELOVL4 were observed as only weak. In addition, ELOVL4ΔC is able to form an elongase complex by interacting with other components of the VLCFA elongation machinery, similar to wild-type ELOVL4. CONCLUSIONS: We propose that not only the ELOVL4-ELOVL4ΔC homo-oligomeric interaction, but also several hetero-oligomeric interactions, may contribute to the pathology of STGD3.

• リゾリン脂質アシル基転移酵素による酸化リン脂質の生合成経路の解明
  前川大志; 前川大志; 山本貴大; 橋本怜暉; 岩尾鳳紀; 青柳良平; 永沼達郎; 大場陽介; 大場陽介; 津川裕司; 津川裕司; 津川裕司; 有田誠; 有田誠; 有田誠; 有田誠, 日本生化学会大会(Web), 96th, 2023年
• アトピー性皮膚炎の病態形成におけるセラミド代謝異常
  飯野雄大; 飯野雄大; 永沼達郎; 永沼達郎; 有田誠; 有田誠; 有田誠, 脂質生化学研究, 64, 2022年
• 皮膚炎の進行に伴う脂肪酸代謝変動とその役割の包括的解析
  藤波和夏; 藤波和夏; 磯部洋輔; 磯部洋輔; 磯部洋輔; 永沼達郎; 有田誠; 有田誠; 有田誠, 次世代を担う若手のためのファーマ・バイオフォーラム講演要旨集, 21st, 2022年
• Jak1シグナルの亢進による皮膚バリア脂質異常についてのリピドミクス解析
  飯野雄大; 飯野雄大; 永沼達郎; 永沼達郎; 有田誠; 有田誠; 有田誠, JSBMS Letters, 46, Supplement, 2021年
• 皮膚の多彩な脂質代謝を捉える包括的メタボローム解析技術
  永沼達郎, 進化する皮膚科学, 245, 253, 2021年, ［筆頭著者］
• 皮膚疾患とリピドミクス
  飯野雄大; 永沼達郎; 有田誠, 医学のあゆみ, 270, 5, 409, 415, 2019年08月, ［招待有り］
  医歯薬出版, 日本語, 記事・総説・解説・論説等（学術雑誌）
• 酸化脂肪酸の膜リン脂質アシル化を担う酵素の探索と機能解析
  橋本怜暉; 橋本怜暉; 青柳良平; 青柳良平; 青柳良平; 永沼達郎; 永沼達郎; 永沼達郎; 有田誠; 有田誠; 有田誠, 次世代を担う若手ファーマ・バイオフォーラム講演要旨集, 17th, 2018年

• アトピー性皮膚炎および乾癬モデルマウスにおける皮膚バリア機能低下とセラミド組成変化
  野坂奈生; 永沼達郎; 木原章雄
  第18回セラミド研究会学術集会, 2025年09月05日
• アトピー性皮膚炎および乾癬モデルマウスにおけるセラミド組成変化
  野坂奈生; 永沼達郎; 木原章雄
  第62回日本生化学会北海道支部例会, 2025年07月14日
• 表皮セラミド分解と恒常性維持における酸性セラミダーゼASAH1の関与
  信本和奏; 永沼達郎; 木原章雄
  第67回脂質生化学会, 2025年06月09日
  2025年 - 2025年
• 2-水酸化脂肪酸のα酸化不全は雄性不妊を引き起こす
  永沼達郎; 木原章雄
  第17回セラミド研究会学術集会, 2024年09月19日
• 酸性セラミダーゼ ASAH1 による表皮セラミドの恒常性維持
  信本和奏; 永沼達郎; 木原章雄
  第61回日本生化学会北海道支部例会, 2024年07月22日
• 脂肪族アシルCoA還元酵素FAR1のセミノリピド合成と精子形成における役割
  玉澤彩乃; 永沼達郎; 永沼達郎; 永沼達郎; 大塚賢人; 佐々貴之; 佐々貴之; 佐々貴之; 木原章雄; 木原章雄; 木原章雄
  第97回日本生化学会大会, 2024年11月06日
  2024年 - 2024年
• 雄性生殖機能における2-水酸化脂肪酸α酸化の役割
  永沼達郎; 木原章雄
  第66脂質生化学会, 2024年06月06日
  2024年 - 2024年
• リゾリン脂質アシル基転移酵素による酸化リン脂質の選択的生合成
  前川大志; 前川大志; 山本貴大; 橋本怜暉; 岩尾鳳紀; 青柳良平; 永沼達郎; 大場陽介; 大場陽介; 津川裕司; 有田誠; 有田誠; 有田誠
  脂質生化学研究, 2023年
  2023年 - 2023年
• 皮膚炎発症過程における脂質代謝変化の包括的リピドミクス解析
  永沼達郎
  バイオメディカル分析科学シンポジウム講演要旨集, 2023年
  2023年 - 2023年
• リゾリン脂質アシル基転移酵素による酸化リン脂質の生合成経路の解明
  前川大志; 前川大志; 山本貴大; 橋本怜暉; 岩尾鳳紀; 青柳良平; 永沼達郎; 大場陽介; 大場陽介; 津川裕司; 津川裕司; 津川裕司; 有田誠; 有田誠; 有田誠; 有田誠
  日本生化学会大会(Web), 2023年
  2023年 - 2023年
• アトピー性皮膚炎の病態形成におけるセラミド代謝異常
  飯野雄大; 飯野雄大; 永沼達郎; 永沼達郎; 有田誠; 有田誠; 有田誠
  脂質生化学研究, 2022年
  2022年 - 2022年
• 皮膚炎の進行に伴う脂肪酸代謝変動とその役割の包括的解析
  藤波和夏; 藤波和夏; 磯部洋輔; 磯部洋輔; 磯部洋輔; 永沼達郎; 有田誠; 有田誠; 有田誠
  次世代を担う若手のためのファーマ・バイオフォーラム講演要旨集, 2022年
  2022年 - 2022年
• Jak1シグナルの亢進による皮膚バリア脂質異常についてのリピドミクス解析
  飯野雄大; 飯野雄大; 永沼達郎; 永沼達郎; 有田誠; 有田誠; 有田誠
  JSBMS Letters, 2021年
  2021年 - 2021年
• 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年06月
  2020年06月 - 2020年06月
• 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
  永沼達郎; 飯野雄大; 平野愛美; 岡村真宜; 有田誠
  第62回 JCBL, 2020年04月, 日本語, 口頭発表（一般）
  2020年04月 - 2020年04月, ［国内会議］
• 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
  森本亜里; 伊東可寛; 佐々木貴史; 塩濱愛子; 川崎洋; 川上英良; 永沼達郎; 有田誠; 古関明彦; 松井毅; 天谷雅行
  第41回日本炎症・再生医学会, 2020年02月
  2020年02月 - 2020年02月
• 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
  中野裕介; 永沼達郎; 有田誠
  第92回 日本生化学会大会, 2019年09月, 日本語, ポスター発表
  2019年09月 - 2019年09月, ［国内会議］
• 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
  平野愛美; 永沼達郎; 有田誠
  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年09月, 日本語, 口頭発表（一般）
  2019年09月 - 2019年09月, ［国内会議］
• アレルギー性接触性皮膚炎の病態制御に関わる脂肪酸代謝系の包括的解析
  平野愛美; 永沼達郎; 有田誠
  第61回脂質生化学会, 2019年07月, 日本語, 口頭発表（一般）
  2019年07月 - 2019年07月, ［国内会議］
• Untargeted lipidomics revealed dysregulated ceramide metabolism in the initiation phase of atopic dermatitis
  Yudai Iino; Tatsuro Naganuma; Makoto Arita
  60th International Conference on the Bioscience of Lipids, 2019年06月, 英語, 口頭発表（一般）
  2019年06月 - 2019年06月, ［国際会議］
• 皮膚の網羅的リピドミクスと疾患モデルへの適用
  永沼達郎; 飯野雄大; 有田誠
  第11回セラミド研究会学術集会, 2018年10月26日, 日本語, 口頭発表（招待・特別）
  2018年10月26日 - 2018年10月26日, ［招待講演］, ［国内会議］
• Untargeted analysis of skin lipid profiles in the development of dermatitis
  Tatsuro Naganuma; Yudai Iino; Makoto Arita
  Japan-Korea Joint Lipid Symposium, 2018年09月14日, 英語, 口頭発表（一般）
  2018年09月14日 - 2018年09月14日, ［国際会議］
• アトピー性皮膚炎マウスにおける脂質代謝異常の網羅的解析
  飯野雄大; 永沼達郎; 有田誠
  第17回次世代を担う若手ファーマ・バイオフォーラム2018, 2018年09月01日, 日本語, 口頭発表（一般）
  2018年09月01日 - 2018年09月01日, ［国内会議］
• 皮膚のリポクオリティの包括的解析とアトピー性皮膚炎モデルへの適用
  飯野雄大; 永沼達郎; 有田誠
  新学術領域研究「脂質クオリティが解き明かす生命現象」第4回班会議, 2018年06月18日, 日本語, 口頭発表（一般）
  2018年06月18日 - 2018年06月18日, ［国内会議］
• アトピー性皮膚炎発症に関わる脂質代謝系の網羅的メタボローム解析
  飯野雄大; 永沼達郎; 有田誠
  第60回日本脂質生化学会, 2018年05月31日, 日本語, 口頭発表（一般）
  2018年05月31日 - 2018年05月31日, ［国内会議］
• 酸化脂肪酸の膜リン脂質アシル化を担う酵素の探索と機能解析
  橋本怜暉; 橋本怜暉; 青柳良平; 青柳良平; 青柳良平; 永沼達郎; 永沼達郎; 永沼達郎; 有田誠; 有田誠; 有田誠
  次世代を担う若手ファーマ・バイオフォーラム講演要旨集, 2018年
  2018年 - 2018年
• 魚鱗癬原因遺伝子Nipal4ノックアウトマウスにおける皮膚バリア脂質アシルセラミドの減少
  本多湧一; 北村拓也; 永沼達郎; 大野祐介; 佐々貴之; 木原章雄
  2017年度生命科学系学会合同年次大会, 2017年12月06日, 日本語
  2017年12月06日 - 2017年12月06日, ［国内会議］
• 魚鱗癬原因遺伝子NIPAL4の欠損によるアシルセラミド産生低下と皮膚バリア機能異常
  本多湧一; 北村拓也; 永沼達郎; 大野祐介; 佐々貴之; 木原章雄
  第16回次世代を担うファーマ・バイオフォーラム2017, 2017年09月09日, 日本語, 口頭発表（一般）
  2017年09月09日 - 2017年09月09日, ［国内会議］
• Skin Homeostasis and Lipid Metabolism
  HNAGANUMA Tatsuro; HR
  University of Strasbourg-RIKEN Workshop on Membrane Lipidology, 2017年03月09日, 英語, 口頭発表（一般）
  2017年03月09日 - 2017年03月09日, ［国際会議］
• 遺伝子欠損マウスを用いた魚鱗癬原因遺伝子 NIPAL4/ICHTHYIN の皮膚バリア形成における機能解析.
  本多湧一; 北村拓也; 永沼達郎; 大野祐介; 木原章雄
  第9回セラミド研究会学術集会, 2016年10月28日, 日本語, 口頭発表（一般）
  2016年10月28日 - 2016年10月28日, ［国内会議］
• Decrease in 2-hydroxygalactosylceramide and impairment in behavioral tests in Aldh3a2 knockout mice.
  Sassa T; Kanetake T; Takagi S; Nojiri K; Naganuma T; Kitamura T; Kihara A
  57th International Conference on the Bioscience of Lipids, 2016年09月, 英語
  2016年09月 - 2016年09月, ［国際会議］
• シェーグレン・ラルソン症候群モデルマウスを用いた病態のメカニズム解析.
  木原章雄; 永沼達郎; 金武司; 佐々貴之
  第11回スフィンゴテラピィ研究会, 2016年07月16日, 日本語
  2016年07月16日 - 2016年07月16日, ［国内会議］
• Retarded skin barrier recovery and an increased keratinocyte growth in Sjögren-Larsson syndrome gene ALDH3A2 knockout mice.
  H永沼 達郎; HR
  1st Korea-Japan Bioactive Lipid Joint Symposium, 2016年05月11日, 英語, 口頭発表（一般）
  2016年05月11日 - 2016年05月11日, ［国際会議］

• 生命薬学特論, 2024年, 修士課程, 生命科学院
• 先端生物科学実験法Ⅰ, 2024年, 学士課程, 薬学部
• 物理化学実習, 2024年, 学士課程, 薬学部
• 薬剤学実習, 2024年, 学士課程, 薬学部

• 日本生化学会
• セラミド研究会

• 精子の特殊なスフィンゴ脂質の代謝機構と雄性生殖機能の制御
  科学研究費助成事業
  2025年04月01日 - 2028年03月31日
  永沼 達郎
  日本学術振興会, 基盤研究(C), 北海道大学, 25K09952
• 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
  科学研究費補助金(文部科学省・日本学術振興会)
  2019年04月 - 2021年03月
  永沼 達郎
  皮膚の恒常性は，種々の脂質分子が独自の機能を発揮することで維持されており，脂質代謝バランスの破綻はアトピー性皮膚炎をはじめとした様々な皮膚疾患の発症に関与すると考えられている。皮膚炎病態に関わる脂質代謝異常を明らかにするには，病態形成に伴う脂質代謝変動を網羅的かつ継時的に解析することが肝要である。我々は，LC-MS/MSを用いたリピドミクス解析により，アトピー様皮膚炎を自然発症するモデルマウスにおける脂質代謝変動を発症前から継時的に解析し，皮膚炎発症および悪化に関わる脂質組成異常を明らかにするとともに，脂質組成に異常を生じる原因となる酵素反応を示唆した。
  日本学術振興会, 若手研究, 慶應義塾大学, 研究代表者, 競争的資金, 19K17816
• 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
  第27回研究奨励助成
  2019年04月 - 2020年03月
  永沼達郎
  小野医学研究財団, 研究代表者, 競争的資金
• 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
  挑戦的研究助成
  2017年04月 - 2020年03月
  セコム科学技術振興財団, 研究代表者, 競争的資金
• 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
  科学研究費補助金(文部科学省・日本学術振興会）
  2017年04月 - 2019年03月
  日本学術振興会, 研究代表者, 競争的資金
• ω3脂肪酸による皮膚恒常性制御機構の解析
  福澤諭吉記念基金
  2017年04月 - 2018年03月
  慶應義塾大学, 競争的資金
• 皮膚炎発症の抑制に関わる脂肪酸代謝物の探索と分子メカニズムの解析
  慶應義塾学事振興資金
  2017年04月 - 2018年03月
  慶應義塾大学, 競争的資金