Soga, Tomoyoshi

写真a

Affiliation

Faculty of Environment and Information Studies （Shonan Fujisawa）

Position

Professor

Related Websites

External Links
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Message from the Faculty Member 【 Display / hide 】

  • 自分のこれまでの経験では、実験がうまくいってもそこから得られるものは何もありません。失敗して、原因をあれこれ考えることで自分が知らなかった知見を得たり、新しい発見をしたりします。したがって、多くのことに果敢にチェレンジしてたくさんの失敗を重ねて欲しいと思います。失敗が必ず皆さんの糧になります。

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Career 【 Display / hide 】

  • 1984.04
    -
    1992.03

    Application Chemist, Yokogawa Corp.

  • 1992.04
    -
    2001.03

    Yokogawa Analytical Systems Inc.

  • 2001.04
    -
    2002.03

    University of the Ryukyus, Visiting Professor

  • 2001.04
    -
    2005.03

    Faculty of Environmental Information/ Institute for Advanced Biosciences, Associate Professor

  • 2003.07
    -
    2010.03

    Human Metabolome Technologies Inc., Director

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Academic Degrees 【 Display / hide 】

  • Ph.D., Toyohashi University of Technology, Dissertation, 2000.03

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Research Themes 【 Display / hide 】

  • 枯草菌、大腸菌、酵母等のバクテリアからイネやマウスの組織、ヒトの血液、尿、赤血球、ガン細胞等のあらゆる生物種の細胞内全代謝物質（メタボローム）の測定法, 

    　

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Books 【 Display / hide 】

  • Amino Acid Analysis : Methods and Protocols

    Alterman M.Ed., (Hirayama, A., Ikeda, S., Sato, A., Soga, T., contribution for Chapter 23）, Humana Press, 2019.07

    Scope: Chapter 23: Amino Acid Analysis by Capillary Electrophoresis-Mass Spectrometry,  Contact page： 307-313

    　View Summary

    Capillary electrophoresis-mass spectrometry (CE-MS) has been developed as a powerful tool in the analysis of charged compounds. To simultaneously analyze free amino acids, an electrolyte with low pH was used to positively charge all of the amino acids. In this condition, all protonated amino acids migrated toward the cathode in CE and then were sensitively and selectively detected by MS. This method is simple, rapid, and selective and could readily be applied to the analysis of free amino acids in various samples. In this chapter, the detailed procedure to analyze amino acids using CE-tandem mass spectrometry (MS/MS) is described.

  • Oceanography Challenges to Future Earth : Human and Natural Impacts on our Seas

    Komatsu, T., Ceccaldi, H-J., Yoshida, J., Prouzet, P., Henocque, Y. Ed., (Nakano, T., Shirakawa, H., Yeo, G., Devlin, R.H., Soga, T., contribution for Part IV ), Springer, 2019.02,  Page： 430

    Scope: Part IV Innovative Research: Metabolome profiling of growth hormone transgenic coho salmon by capillary electrophoresis time-of-flight mass spectrometry,  Contact page： 223-234

  • Capillary Electrophoresis-Mass Spectrometry for Metabolomics

    Ramautar R. Ed., (Hirayama A, Soga T. contribution for CHAPTER 7), The Royal Society of Chemistry, 2018.07,  Page： 300

    Scope: CHAPTER 7: CE-MS for anionic and cationic metabolic profiling: system optimization and applications,  Contact page： 134-160

  • ONCO-METABOLOMICS; A NEW CLUE TO UNDERSTAND CARCINOGENESIS, CANCER BIOLOGY AND TO DEVELOP NOVEL DIAGNOSTICS AND THERAPEUTICS

    Esmi, H., Mak, T.W., Soga, T., Suematsu, M.,Mori, M. Ed, Princess Takamatsu Cancer Research Fund, 2016.04

  • Metabolomics: Methods and Protocols

    Bjerrum, J. T. Ed. (Wakayama, M., Hirayama, A., Soga, T., contribution for Chapter 13), Humana Press, 2015.04,  Page： 269

    Scope: Chapter 13: Capillary Electrophoresis-Mass Spectrometry,  Contact page： 113-122

    　View Summary

    Capillary electrophoresis-mass spectrometry (CE-MS) has proven to be useful for metabolomics studies. Charged metabolites are first separated by CE based on charge and size and are subsequently selectively detected using MS. The major advantages of CE-MS are its high resolution and the fact that almost any charged species can be analyzed by two methods, both cationic and anionic. This technique can readily be applied to various types of biological samples originating from bacteria, plants, mammals, and body fluids. This chapter highlights detailed practical procedures for using this technology.

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Papers 【 Display / hide 】

  • Cardiac Mitofusin-1 is Reduced in Non-responding Patients with Idiopathic Dilated Cardiomyopathy

    Hsiao, Y.T., Shimizu, I., Wakasugi, T., Yoshida, Y., Ikegami, R., Hayashi, Y., Suda, M., Katsuumi, G., Nakao, M., Ozawa, T., Izumi, D., Kashimura, T., Ozaki, K., Soga, T., Minamino, T.

    Sci. Rep 11 （ 1 ） 6722 2021.03

    Research paper (scientific journal), Joint Work, Accepted

    　View Summary

    Prognosis of severe heart failure remains poor. Urgent new therapies are required. Some heart failure patients do not respond to established multidisciplinary treatment and are classified as "non-responders". The outcome is especially poor for non-responders, and underlying mechanisms are largely unknown. Mitofusin-1 (Mfn1), a mitochondrial fusion protein, is significantly reduced in non-responding patients. This study aimed to elucidate the role of Mfn1 in the failing heart. Twenty-two idiopathic dilated cardiomyopathy (IDCM) patients who underwent endomyocardial biopsy of intraventricular septum were included. Of the 22 patients, 8 were non-responders (left ventricular (LV) ejection fraction (LVEF) of < 10% improvement at late phase follow-up). Electron microscopy (EM), quantitative PCR, and immunofluorescence studies were performed to explore the biological processes and molecules involved in failure to respond. Studies in cardiac specific Mfn1 knockout mice (c-Mfn1 KO), and in vitro studies with neonatal rat ventricular myocytes (NRVMs) were also conducted. A significant reduction in mitochondrial size in cardiomyocytes, and Mfn1, was observed in non-responders. A LV pressure overload with thoracic aortic constriction (TAC) c-Mfn1 KO mouse model was generated. Systolic function was reduced in c-Mfn1 KO mice, while mitochondria alteration in TAC c-Mfn1 KO mice increased. In vitro studies in NRVMs indicated negative regulation of Mfn1 by the β-AR/cAMP/PKA/miR-140-5p pathway resulting in significant reduction in mitochondrial respiration of NRVMs. The level of miR140-5p was increased in cardiac tissues of non-responders. Mfn1 is a biomarker of heart failure in non-responders. Therapies targeting mitochondrial dynamics and homeostasis are next generation therapy for non-responding heart failure patients.

  • Trans-Omic Analysis Reveals Obesity-Associated Dysregulation of Inter-Organ Metabolomic Cycles between the Liver and Skeletal Muscle

    Egami, R., Kokaji, T., Hatano, A., Yugi, K., Eto, M., Morita, K., Ohno, S., Fujii, M., Hironaka, K., Uematsu, S., Terakawa, A., Bai, Y., Pan, Y., Tsuchiya, T., Ozaki, H., Inoue, H., Uda, S., Kubota, H., Suzuki, Y., Matsumoto, M., Nakayama, K., Hirayama, A., Soga, T., Kuroda, S.

    iScience  24 （ 3 ） 102217 2021.03

    Research paper (scientific journal), Joint Work, Accepted

    　View Summary

    Systemic metabolic homeostasis is regulated by inter-organ metabolic cycles involving multiple organs. Obesity impairs inter-organ metabolic cycles, resulting in metabolic diseases. The systemic landscape of dysregulated inter-organ metabolic cycles in obesity has yet to be explored. Here, we measured the transcriptome, proteome, and metabolome in the liver and skeletal muscle and the metabolome in blood of fasted wild-type and leptin-deficient obese (ob/ob) mice, identifying components with differential abundance and differential regulation in ob/ob mice. By constructing and evaluating the trans-omic network controlling the differences in metabolic reactions between fasted wild-type and ob/ob mice, we provided potential mechanisms of the obesity-associated dysfunctions of metabolic cycles between liver and skeletal muscle involving glucose-alanine, glucose-lactate, and ketone bodies. Our study revealed obesity-associated systemic pathological mechanisms of dysfunction of inter-organ metabolic cycles.

  • MEK inhibition preferentially suppresses anchorage-independent growth in osteosarcoma cells and decreases tumors in vivo

    Shimizu, T., Kimura, K., Sugihara, E., Yamaguchi-Iwai, S., Nobuse, H., Sampetrean, O., Otsuki, Y., Fukuchi, Y., Saitoh, K., Kato, K., Soga, T., Muto, A., Saya, H.

    J. Orthop. Res. online 2021.03

    Research paper (scientific journal), Joint Work, Accepted

    　View Summary

    Osteosarcoma is the most common high-grade malignancy of bone, and novel therapeutic options are urgently required. Previously, we developed mouse osteosarcoma AXT cells that can proliferate both under adherent and nonadherent conditions. Based on metabolite levels, nonadherent conditions were more similar to the in vivo environment than adherent conditions. A drug screen identified MEK inhibitors, including trametinib, that preferentially decreased the viability of nonadherent AXT cells. Trametinib inhibited the cell cycle and induced apoptosis in AXT cells, and both effects were stronger under nonadherent conditions. Trametinib also potently decreased viability in U2OS cells, but its effects were less prominent in MG63 or Saos2 cells. By contrast, MG63 and Saos2 cells were more sensitive to PI3K inhibition than AXT or U2OS cells. Notably, the combination of MAPK/ERK kinase (MEK) and PI3K inhibition synergistically decreased viability in U2OS and AXT cells, but this effect was less pronounced in MG63 or Saos2 cells. Therefore, signal dependence for cell survival and crosstalk between MEK-ERK and PI3K-AKT pathways in osteosarcoma are cell context-dependent. The activation status of other kinases including CREB varied in a cell context-dependent manner, which might determine the response to MEK inhibition. A single dose of trametinib was sufficient to decrease the size of the primary tumor and circulating tumor cells in vivo. Moreover, combined administration of trametinib and rapamycin or conventional anticancer drugs further increased antitumor activity. Thus, given optimal biomarkers for predicting its effects, trametinib holds therapeutic potential for the treatment of osteosarcoma.

  • Quantitative and Molecular Similarity Analyses of the Metabolites of Cold- and Hot-Natured Chinese Herbs

    Guo, J., Wang, J., Iino, K., Tomita, M., Soga, T.

    Evid. Based. Complement. Alternat. Med. 2021   6646507 2021.03

    Research paper (scientific journal), Joint Work, Accepted

    　View Summary

    Background. Based on the theory of traditional Chinese medicine, Chinese herbs possess four different medicinal properties: hot, warm, cold, and cool. These serve as a reference guide for these herbal medicines. However, the molecular mechanisms supporting their relevance remain unclear. Methods. We performed metabolomics based on capillary electrophoresis-time-of-flight mass spectrometry (CE-TOF/MS) and multivariate data analysis for the structural identification of compounds of cold- and hot-natured Chinese herbs. Results. To this end, 30 selected herbs were analyzed and a total of 416 metabolites were identified via CE-TOF/MS, of which 193 compounds were detected in most herbs. The observed profiles offered the potential to understand the mechanism of association between the compounds and nature of the Chinese herbs. Comparison of the similarity in terms of chemical and molecular structures and content revealed that hot-natured herbs contained more nucleotides. In contrast, principal component analysis revealed the presence of more amino acid compounds in cold-natured herbs. Conclusion. Comparing the structural similarities between the samples using the Tanimoto coefficient revealed that a general non-specific structure was observed between cold- and hot-natured herbs; however, the distribution of the molecular groups seemed to contribute more toward the energy properties.

  • Reprogramming of glutamine metabolism via glutamine synthetase silencing induces cisplatin resistance in A2780 ovarian cancer cells

    Guo, J., Satoh, K., Tabata, S., Mori, M., Tomita, M., Soga, T.

    BMC Cancer 21 （ 1 ） 174 2021.02

    Research paper (scientific journal), Joint Work, Accepted

    　View Summary

    Background: Cisplatin (CDDP) significantly prolongs survival in various cancers, but many patients also develop resistance that results in treatment failure. Thus, this study aimed to elucidate the underlying mechanisms by which ovarian cancer cells acquire CDDP resistance.
    Methods: We evaluated the metabolic profiles in CDDP-sensitive ovarian cancer A2780 cells and CDDP-resistant A2780cis cells using capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS). We further examined the expression of glutamine metabolism enzymes using real-time PCR and Western blot analyses. Cell viability was accessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.
    Results: The results showed that levels of glutamine, glutamate, and glutathione (GSH), a key drug resistance mediator synthesized from glutamate, were significantly elevated in A2780cis cells than those in A2780 cells. Furthermore, glutamine starvation decreased the GSH levels and CDDP resistance in A2780cis cells. Interestingly, the expression of glutamine synthetase (GS/GLUL), which synthesizes glutamine from glutamate and thereby negatively regulates GSH production, was almost completely suppressed in resistant A2780cis cells. In addition, treatment of A2780cis cells with 5-aza-2'-deoxycytidine, a DNA-demethylating agent, restored GS expression and reduced CDDP resistance. In contrast, GS knockdown in CDDP-sensitive A2780 cells induced CDDP resistance.
    Conclusions: The results indicate that upregulation of GSH synthesis from glutamine via DNA methylation-mediated silencing of GS causes CDDP resistance in A2780cis cells. Therefore, glutamine metabolism could be a novel therapeutic target against CDDP resistance.

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

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Reviews, Commentaries, etc. 【 Display / hide 】

  • メタボロミクスによるがん幹細胞の代謝研究

    北島正二朗、曽我朋義

    （別冊 医学のあゆみ）　治療標的としてのがん幹細胞 (Ishiyaku Pub,Inc.)     117 - 121 2021.03

    Introduction and explanation (scientific journal), Joint Work

  • メタボローム解析に基づく癌診断法の開発

    Soga, T., Sugimoto, M.

    Gastroenterology & Hepatology (Kagakuhyoronsya Co., Ltd.)  8 ( 2 ) 137 - 143 2020.08

    Joint Work

  • はじめに-メタボローム解析UPDATE

    Soga, T.

    （別冊・医学のあゆみ） メタボローム解析UPDATE (Ishiyaku Pub,Inc.)   2020.06

    Single Work

  • メタボロミクスによるがん幹細胞の代謝研究

    Kitajima, S., Soga, T.

    Journal of Clinical and Experimental Medicine（IGAKU NO AYUMI） (Ishiyaku Pub,Inc.)  273 ( 5 ) 469 - 473 2020.05

    Introduction and explanation (scientific journal), Joint Work

  • はじめに-メタボローム解析UPDATE

    Soga, T.

    Journal of Clinical and Experimental Medicine（IGAKU NO AYUMI） (Ishiyaku Pub,Inc.)  270 ( 5 ) 377 - - 2019.08

    Introduction and explanation (scientific journal)

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Presentations 【 Display / hide 】

  • Multi Omics analysis of colorectal cancer metabolism

    2018 International Meeting on 22nd MDO and 33rd JSSX (Ishikawa Ongakudo, Kanazawa, Ishikawa) , 2018.10, Oral Presentation(guest/special), JSSX (The Japanese Society for the Study of Xenobiotics)、MDO(Microsomes and Drug Oxidations)

  • Malti-omics reveals MYC as a master regulator of colorectal cancer metabolism

    SOGA TOMOYOSHI

    The 1st International Symposium for Trans-Omics (Koshiba Hall, The University of Tokyo, Hongo Campus) , 2017.11, Oral Presentation(guest/special)

  • Onco-metabolites and cancer specific metabolic pathways

    SOGA TOMOYOSHI

    American Association for Cancer Research Annual Meeting 2017, AACR2017, 2017.04, Oral Presentation(guest/special)

  • What Causes Altered Metabolism in Colon Cancer Cells

    SOGA TOMOYOSHI

    46th International Symposium of The Princess Takamatsu Cancer Research Found (Palece Hotel Tokyo, Japan) , 2015.11, Oral Presentation(guest/special)

  • CE-MS Metabolomics and Application to Cancer cell Metabolism

    SOGA TOMOYOSHI

    11th International Conference of the Metabolomics Society, Metabolomics 2015, (Hyatt Regency San Francisco Airport, Burlingame, California, USA) , 2015.07, Oral Presentation(guest/special)

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

  • Drug development targeting metabolic vulnerability of SUCLA2 deletion

    2019.08
    -
    2021.03

    Japan Agency for Medical Research and Development(AMED), Project for Cancer Research and Therapeutic Evolution (P-CREATE) , TAKAHASHI Chiaki, No Setting, Co-investigator

  • Development of risk prediction models for mild cognitive decline and frailty using metabolomics in a population-based cohort

    2018.04
    -
    2023.03

    Ministry of Education,Culture,Sports,Science and Technology(MEXT)/Japan Society for the Promotion of Science(JSPS) , Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A), Takebayashi, Toru, Research grant, Co-investigator

  • Metabolomic analysis for the mechanisms of treatment resistance during neoadjuvant chemoradiotherapy in patients with pancreatic adenocarcinoma

    2018.04
    -
    2021.03

    Ministry of Education,Culture,Sports,Science and Technology(MEXT)/Japan Society for the Promotion of Science(JSPS) , Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Okano, Keiichi, No Setting, Co-investigator

  • Elucidation of molecular machineries for the regulation of myeloid leukemia stem cells

    2016.04
    -
    2021.03

    Ministry of Education,Culture,Sports,Science and Technology(MEXT)/Japan Society for the Promotion of Science(JSPS) , Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (S) , Akashi, Koichi, Grant-in-Aid for Scientific Research (S), Research grant, Co-investigator

  • Metabolome-wide metabolic profiling and non-communicable disease prevention in a population-based cohort study

    2015.04
    -
    2018.03

    Ministry of Education,Culture,Sports,Science and Technology(MEXT)/Japan Society for the Promotion of Science(JSPS) , Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B), Takebayashi, Toru, Research grant, Co-investigator

    　View Remarks

    基盤Aが採択されたことにより、基盤BについてはH29(2017)年度で終了

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Works 【 Display / hide 】

  • 経済産業省主催「バイオ人材育成事業」メタボローム実習講師

    SOGA TOMOYOSHI

    2004.12
    , 

    Other, Joint

  • 日経BP社主催バイオファイナンスギルド　メタボローム講座

    SOGA TOMOYOSHI

    2004.08
    , 

    Other, Joint

  • キャピラリー電気泳動による無機陰イオン、有機酸、アミノ酸の分析

    そがともよし

    2001.10
    -
    Present
    , 

    Other

    　View Details

    キャピラリー電気泳動法の装置、測定法の原理および様々な測定例を解説した

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Awards 【 Display / hide 】

  • The 2nd Shigeru Terabe Award

    2015.11,  Division of Electrophoresis, Japan Society for Analytical Chemistry, CE-MSメタボローム測定技術の開発と実用化

    Type of Award： Awards of National Conference, Council and Symposium.  Country： 日本

  • Keio Award

    SOGA Tomoyoshi, 2011.11, Keio University, CE-MSメタボローム測定技術の開発と実用化

    Type of Award： Keio commendation etc.

  • 第7回酸化ストレスと肝研究会　奨励賞

    SOGA Tomoyoshi, 2010.11, 酸化ストレスと肝研究会, メタボロミクスによる新規酸化ストレスマーカーの同定と肝臓疾患スクリーニング

    Type of Award： Awards of National Conference, Council and Symposium

    　View Description

    第7回酸化ストレスと肝研究会における研究発表による

  • The prize of the chairman of HATSUMEI KYOKAI

    SOGA Tomoyoshi, 2009.07, Japan Institute of Invention and Innovation, Apparatus and Method for Metabolome Analysis

    Type of Award： Other Awards

  • The Minister of Education, Culture, Sports, Science& Technology Award

    SOGA Tomoyoshi, TOMITA Masaru, 2007.04, Minister of Education, Culture, Sports, Science& Technology, メタボローム解析技術に基づくバイオマーカーの探索研究

    Type of Award： Other Awards

    　View Description

    細胞内に存在する数千種類の代謝物質を一斉に分析する分析技術を世界に先駆けて開発した。代謝物質のほとんどがイオン性を持つことに着目し、イオン性物質に対して高分離能を有するキャピラリー電気泳動（CE）と高選択・高感度検出器である質量分析計（MS）を組み合わせた独創的なものである。数千種類の代謝物質の変化を瞬時に可視化する情報処理技術も開発した。本研究により、急性肝炎時に血中で急増するバイオマーカーと、特定のがん細胞にのみ増加するバイオマーカー候補をすでに発見した。本成果は、バイオマーカーの探索にブレイクスルーをもたらすものであり、医薬分野の進展を促進することが期待される。

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Courses Taught 【 Display / hide 】

  • SEMINAR B

    2021

  • METABOLOMICS

    2021

  • METABOLOME ANALYSIS LABORATORY PRACTICE

    2021

  • MASTER SEMINAR

    2021

  • INDEPENDENT RESEARCH

    2021

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