Takahashi, Shinichi

写真a

Affiliation

Keio Frontier Research & Education Collaborative Square (K-FRECS), K-FRECS at Tonomachi (Mita)

Position

Project Professor (Non-tenured)

Remarks

Shin Takahashi

External Links
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Career 【 Display / hide 】

  • 1987.04
    -
    1991.03

    keio University Hospital, Internal Medicine, resident

  • 1991.04
    -
    1997.05

    Keio University Hospital, Internal Medicine, senior resident

  • 1992.02
    -
    1995.03

    National Institute of Mental Health, Laboratory of Cerebral Metabolism, visiting fellow

  • 1995.04

    keio University Hospital, Devision of Neurology, Department of Internal Medicine, instructor

  • 1995.05
    -
    1997.06

    Urawa Municipal Hospital, Neurology, 医員

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Academic Background 【 Display / hide 】

  • 1981.04
    -
    1987.03

    Keio University, School of Medicine

    University, Graduated

  • 1987.04
    -
    1991.03

    keio University, Graduate School of Medicine, Internal Medicine

    Graduate School, Completed, Doctoral course

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Academic Degrees 【 Display / hide 】

  • 医学博士, Keio University, Coursework, 1991.03

    クモ膜下出血における上頸部交感神経節節前線維の電気活動.

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Licenses and Qualifications 【 Display / hide 】

  • 医師免許, 1987.06

  • 日本神経学会専門医, 1991.07

  • 日本脳卒中学会専門医, 2003.03

  • 日本内科学会認定内科医, 2004.04

  • 日本内科学会総合内科専門医, 2016.12

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Research Areas 【 Display / hide 】

  • Life Science / Neurology

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Research Keywords 【 Display / hide 】

  • astrocyte

  • glia

  • microcirculation

  • stroke

  • cerebral blood flow and metabolism

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Research Themes 【 Display / hide 】

  • Integrative regulation of glial cells as the therapeutic strategy of neurological disorders, 

    2015.04
    -
    Present

  • Astroglial function and neurological diseases, 

    1995.04
    -
    Present

  • Flow-metabolism coupling in the brain, 

    1992.02
    -
    Present

  • Regulatory mechanisms of cerebral circulation, 

    1987.04
    -
    Present

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Papers 【 Display / hide 】

  • Proteomic insights into extracellular vesicles in ALS for therapeutic potential of Ropinirole and biomarker discovery

    Kato C., Ueda K., Morimoto S., Takahashi S., Nakamura S., Ozawa F., Ito D., Daté Y., Okada K., Kobayashi N., Nakahara J., Okano H.

    Inflammation and Regeneration 44 ( 1 )  2024.12

    　View Summary

    Background: Extracellular vesicles (EVs) hold the potential for elucidating the pathogenesis of amyotrophic lateral sclerosis (ALS) and serve as biomarkers. Notably, the comparative and longitudinal alterations in the protein profiles of EVs in serum (sEVs) and cerebrospinal fluid (CSF; cEVs) of sporadic ALS (SALS) patients remain uncharted. Ropinirole hydrochloride (ROPI; dopamine D2 receptor [D2R] agonist), a new anti-ALS drug candidate identified through induced pluripotent stem cell (iPSC)-based drug discovery, has been suggested to inhibit ALS disease progression in the Ropinirole Hydrochloride Remedy for Amyotrophic Lateral Sclerosis (ROPALS) trial, but its mechanism of action is not well understood. Therefore, we tried to reveal longitudinal changes with disease progression and the effects of ROPI on protein profiles of EVs. Methods: We collected serum and CSF at fixed intervals from ten controls and from 20 SALS patients participating in the ROPALS trial. Comprehensive proteomic analysis of EVs, extracted from these samples, was conducted using liquid chromatography/mass spectrometer (LC/MS). Furthermore, we generated iPSC-derived astrocytes (iPasts) and performed RNA sequencing on astrocytes with or without ROPI treatment. Results: The findings revealed notable disparities yet high congruity in sEVs and cEVs protein profiles concerning disease status, time and ROPI administration. In SALS, both sEVs and cEVs presented elevated levels of inflammation-related proteins but reduced levels associated with unfolded protein response (UPR). These results mirrored the longitudinal changes after disease onset and correlated with the revised ALS Functional Rating Scale (ALSFRS-R) at sampling time, suggesting a link to the onset and progression of SALS. ROPI appeared to counteract these changes, attenuating inflammation-related protein levels and boosting those tied to UPR in SALS, proposing an anti-ALS impact on EV protein profiles. Reverse translational research using iPasts indicated that these changes may partly reflect the DRD2-dependent neuroinflammatory inhibitory effects of ROPI. We have also identified biomarkers that predict diagnosis and disease progression by machine learning-driven biomarker search. Conclusions: Despite the limited sample size, this study pioneers in reporting time-series proteomic alterations in serum and CSF EVs from SALS patients, offering comprehensive insights into SALS pathogenesis, ROPI-induced changes, and potential prognostic and diagnostic biomarkers.

  • Study Profile of the Tsuruoka Metabolomics Cohort Study (TMCS)

    Harada S., Iida M., Miyagawa N., Hirata A., Kuwabara K., Matsumoto M., Okamura T., Edagawa S., Kawada Y., Miyake A., Toki R., Akiyama M., Kawai A., Sugiyama D., Sato Y., Takemura R., Fukai K., Ishibashi Y., Kato S., Kurihara A., Sata M., Shibuki T., Takeuchi A., Kohsaka S., Sawano M., Shoji S., Izawa Y., Katsumata M., Oki K., Takahashi S., Takizawa T., Maruya H., Nishiwaki Y., Kawasaki R., Hirayama A., Ishikawa T., Saito R., Sato A., Soga T., Sugimoto M., Tomita M., Komaki S., Ohmomo H., Ono K., Otsuka-Yamasaki Y., Shimizu A., Sutoh Y., Hozawa A., Kinoshita K., Koshiba S., Kumada K., Ogishima S., Sakurai-Yageta M., Tamiya G., Takebayashi T.

    Journal of epidemiology 34 ( 8 ) 393 - 401 2024.08

    　View Summary

    The Tsuruoka Metabolomics Cohort Study (TMCS) is an ongoing population-based cohort study being conducted in the rural area of Yamagata Prefecture, Japan. This study aimed to enhance the precision prevention of multi-factorial, complex diseases, including non-communicable and aging-associated diseases, by improving risk stratification and prediction measures. At baseline, 11,002 participants aged 35-74 years were recruited in Tsuruoka City, Yamagata Prefecture, Japan, between 2012 and 2015, with an ongoing follow-up survey. Participants underwent various measurements, examinations, tests, and questionnaires on their health, lifestyle, and social factors. This study uses an integrative approach with deep molecular profiling to identify potential biomarkers linked to phenotypes that underpin disease pathophysiology and provide better mechanistic insights into social health determinants. The TMCS incorporates multi-omics data, including genetic and metabolomic analyses of 10,933 participants, and comprehensive data collection ranging from physical, psychological, behavioral, and social to biological data. The metabolome is used as a phenotypic probe because it is sensitive to changes in physiological and external conditions. The TMCS focuses on collecting outcomes for cardiovascular disease, cancer incidence and mortality, disability and functional decline due to aging and disease sequelae, and the variation in health status within the body represented by omics analysis that lies between exposure and disease. It contains several sub-studies on aging, heated tobacco products, and women's health. This study is notable for its robust design, high participation rate (89%), and long-term repeated surveys. Moreover, it contributes to precision prevention in Japan and East Asia as a well-established multi-omics platform.

  • Factors influencing the early neurological deterioration in intracranial branch atheromatous diseases

    Deguchi I., Fujiwara S., Arai N., Nakagami T., Kimura R., Oryu K., Watanabe K., Kato Y., Hayashi T., Takahashi S., Suda S.

    Neurology and Clinical Neuroscience 12 ( 4 ) 217 - 224 2024.07

    　View Summary

    Background: Intracranial branch atheromatous disease (BAD)-type cerebral infarction is often associated with a progressive worsening of neurological symptoms in the acute phase. Aim: To investigate the factors influencing the occurrence of early neurological deterioration (END) in patients with BAD. Methods: We included and evaluated 198 consecutive patients (150 patients with lenticulostriate artery [LSA-BAD] and 48 patients with paramedian pontine artery [PPA-BAD]) with onset within 24 h and with a modified Rankin scale score of ≤1 before admission for END retrospectively out of 235 patients with BAD-type cerebral infarction admitted to our hospital from January 2019 to March 2023. Results: END was observed in 26 (17%) and 15 (31%) patients with LSA-BAD and PPA-BAD, respectively. Patients in the END group with LSA-BAD had significantly higher rates of diabetes mellitus and blood glucose (BG) levels on admission and lower rates of initial clopidogrel loading therapy than those in the non-END group. Patients in the END group with PPA-BAD had significantly higher BG levels on admission than those in the non-END group. In LSA-BAD multivariate analysis, the BG level on admission and initial clopidogrel loading were identified as factors influencing END (BG level [per 10 mg/dL], odds ratio [OR] 1.084, 95% confidence interval [CI] 1.008–1.166; initial clopidogrel loading, OR 0.302, 95% CI 0.101–0.901). Conclusions: Higher BG levels at stroke onset were associated with END in patients with LSA-BAD and PPA-BAD. Additionally, initial clopidogrel loading therapy suppressed END in patients with LSA-BAD.

  • Aberrant CHCHD2-associated mitochondriopathy in Kii ALS/PDC astrocytes

    Leventoux N., Morimoto S., Ishikawa M., Nakamura S., Ozawa F., Kobayashi R., Watanabe H., Supakul S., Okamoto S., Zhou Z., Kobayashi H., Kato C., Hirokawa Y., Aiba I., Takahashi S., Shibata S., Takao M., Yoshida M., Endo F., Yamanaka K., Kokubo Y., Okano H.

    Acta Neuropathologica 147 ( 1 )  2024.06

    ISSN  00016322

    　View Summary

    Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex (ALS/PDC), a rare and complex neurological disorder, is predominantly observed in the Western Pacific islands, including regions of Japan, Guam, and Papua. This enigmatic condition continues to capture medical attention due to affected patients displaying symptoms that parallel those seen in either classical amyotrophic lateral sclerosis (ALS) or Parkinson’s disease (PD). Distinctly, postmortem examinations of the brains of affected individuals have shown the presence of α-synuclein aggregates and TDP-43, which are hallmarks of PD and classical ALS, respectively. These observations are further complicated by the detection of phosphorylated tau, accentuating the multifaceted proteinopathic nature of ALS/PDC. The etiological foundations of this disease remain undetermined, and genetic investigations have yet to provide conclusive answers. However, emerging evidence has implicated the contribution of astrocytes, pivotal cells for maintaining brain health, to neurodegenerative onset, and likely to play a significant role in the pathogenesis of ALS/PDC. Leveraging advanced induced pluripotent stem cell technology, our team cultivated multiple astrocyte lines to further investigate the Japanese variant of ALS/PDC (Kii ALS/PDC). CHCHD2 emerged as a significantly dysregulated gene when disease astrocytes were compared to healthy controls. Our analyses also revealed imbalances in the activation of specific pathways: those associated with astrocytic cilium dysfunction, known to be involved in neurodegeneration, and those related to major neurological disorders, including classical ALS and PD. Further in-depth examinations revealed abnormalities in the mitochondrial morphology and metabolic processes of the affected astrocytes. A particularly striking observation was the reduced expression of CHCHD2 in the spinal cord, motor cortex, and oculomotor nuclei of patients with Kii ALS/PDC. In summary, our findings suggest a potential reduction in the support Kii ALS/PDC astrocytes provide to neurons, emphasizing the need to explore the role of CHCHD2 in maintaining mitochondrial health and its implications for the disease.

  • Cerebral Small Vessel Disease Burden for Bleeding Risk during Antithrombotic Therapy: Bleeding with Antithrombotic Therapy 2 Study

    Tanaka K., Miwa K., Koga M., Yoshimura S., Kamiyama K., Yagita Y., Nagakane Y., Hoshino H., Terasaki T., Okada Y., Yakushiji Y., Takahashi S., Ueda T., Hasegawa Y., Shiozawa M., Sasaki M., Kudo K., Tanaka J., Nishihara M., Yamaguchi Y., Fujita K., Honda Y., Kawano H., Ide T., Yoshimoto T., Ihara M., Hirano T., Toyoda K.

    Annals of Neurology 95 ( 4 ) 774 - 787 2024.04

    ISSN  03645134

    　View Summary

    Objective: This study was undertaken to determine the excess risk of antithrombotic-related bleeding due to cerebral small vessel disease (SVD) burden. Methods: In this observational, prospective cohort study, patients with cerebrovascular or cardiovascular diseases taking oral antithrombotic agents were enrolled from 52 hospitals across Japan between 2016 and 2019. Baseline multimodal magnetic resonance imaging acquired under prespecified conditions was assessed by a central diagnostic radiology committee to calculate total SVD score. The primary outcome was major bleeding. Secondary outcomes included bleeding at each site and ischemic events. Results: Of the analyzed 5,250 patients (1,736 women; median age = 73 years, 9,933 patient-years of follow-up), antiplatelets and anticoagulants were administered at baseline in 3,948 and 1,565, respectively. Median SVD score was 2 (interquartile range = 1–3). Incidence rate of major bleeding was 0.39 (per 100 patinet-years) in score 0, 0.56 in score 1, 0.91 in score 2, 1.35 in score 3, and 2.24 in score 4 (adjusted hazard ratio [aHR] for score 4 vs 0 = 5.47, 95% confidence interval [CI] = 2.26–13.23), that of intracranial hemorrhage was 0.11, 0.33, 0.58, 0.99, and 1.06, respectively (aHR = 9.29, 95% CI = 1.99–43.35), and that of ischemic event was 1.82, 2.27, 3.04, 3.91, and 4.07, respectively (aHR = 1.76, 95% CI = 1.08–2.86). In addition, extracranial major bleeding (aHR = 3.43, 95% CI = 1.13–10.38) and gastrointestinal bleeding (aHR = 2.54, 95% CI = 1.02–6.35) significantly increased in SVD score 4 compared to score 0. Interpretation: Total SVD score was predictive for intracranial hemorrhage and probably for extracranial bleeding, suggesting the broader clinical relevance of cerebral SVD as a marker for safe implementation of antithrombotic therapy. ANN NEUROL 2024;95:774–787.

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

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Reviews, Commentaries, etc. 【 Display / hide 】

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Presentations 【 Display / hide 】

  • シンポジウム１０：「筋萎縮性側索硬化症（ALS）に対する治療の最新情報」．

    'Takahashi,' Shinichi

    第36回日本神経治療学会学術集会（平成30年11月24日、東京）, 

    2018.11
    , 

    Symposium, workshop panel (nominated)

  • シンポジウム１「脳卒中と脳循環代謝」：脳卒中と脳代謝の基礎．

    'Takahashi,' Shinichi

    第61回日本脳循環代謝学会学術集会（平成30年10月19日、盛岡）, 

    2018.10
    , 

    Symposium, workshop panel (nominated)

  • アカデミックレクチャー２：グリア細胞とNeurorehabilitation．

    'Takahashi,' Shinichi

    第９回日本ニューロリハビリテーション学会学術集会 (盛岡) , 

    2018.05
    , 

    Oral presentation (invited, special)

  • NHKラジオ朝一番健康ライフ-- もしかしたらあなたも？脳血管の病気

    'Takahashi,' Shinichi

    NHKラジオ朝一番健康ライフ--, 

    2018.04
    , 

    Media coverage, NHK

  • 教育講演18：脳梗塞急性期のCT、MRI．

    'Takahashi,' Shinichi

    第43回日本脳卒中学会総会（STROKE 2018） (福岡) , 

    2018.03
    , 

    Oral presentation (invited, special)

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

  • ALS運動ニューロン標的iPS細胞創薬から同定された薬物のグリア細胞疾患修飾作用

    2022.04
    -
    2025.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 基盤研究(C), Principal investigator

  • A novel treatment of cerebral infarction with neuroprotective astrocytes induced by inflammatory microglia

    2019.04
    -
    2022.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

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Courses Taught 【 Display / hide 】

  • LECTURE SERIES, INTERNAL MEDICINE

    2023

  • CLINICAL TRAINING IN DIAGNOSIS

    2023

  • LECTURE SERIES, INTERNAL MEDICINE

    2022

  • CLINICAL TRAINING IN DIAGNOSIS

    2022

  • LECTURE SERIES, INTERNAL MEDICINE

    2021

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Courses Previously Taught 【 Display / hide 】

  • クリニカルクラークシップ（基礎ポリクリ）クルズス

    Keio University

    2017.04
    -
    2018.03
    , 

    Lecture

  • 診断学実習　腰椎穿刺

    Keio University

    2017.04
    -
    2018.03
    , 

    Laboratory work/practical work/exercise

  • 診断学実習　OSCE神経診察

    Keio University

    2017.04
    -
    2018.03
    , 

    Laboratory work/practical work/exercise

  • 内科学Ⅱ（神経）

    Keio University

    2017.04
    -
    2018.03
    , 

    Lecture

  • 神経解剖学

    Keio University

    2017.04
    -
    2018.03
    , 

    Lecture

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Social Activities 【 Display / hide 】

  • 社団法人医療系大学間共用試験実施評価機構　医学系OSCE実施小委員会　外部評価者認定専門部会

    2013
    -
    Present

  • 社団法人医療系大学間共用試験実施評価機構　医学系OSCE事後評価解析小委員会 課題改訂専門部会（神経ステーション）

    2009
    -
    Present

  • 科学研究費委員会専門委員

    2013.12
    -
    2015.11

  • Keio Journal of Medicine, Editorial Board

    2012
    -
    Present

  • J Stroke and Cerebrovascular Diseases（日本脳卒中学会英文誌）, Editorial Board

    2017
    -
    Present
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Memberships in Academic Societies 【 Display / hide 】

  • 日本神経学会, 

    1987.05
    -
    Present

  • 日本脳卒中学会, 

    1987.05
    -
    Present

  • 日本内科学会, 

    1988.06
    -
    Present

  • 日本脳循環代謝学会, 

    1988.11
    -
    Present

  • 日本脳ドック学会, 

    2006.06
    -
    Present

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Committee Experiences 【 Display / hide 】

  • 2018
    -
    Present

    学会英文誌「Neurology and Clinical Neuroscience」編集委員, 日本神経学会

  • 2014
    -
    2018

    財務委員会, 日本神経学会

  • 2014
    -
    Present

    専門教育小委員会, 日本神経学会

  • 2013
    -
    Present

    代議員, 日本神経学会

  • 2005
    -
    2013

    評議員, 日本神経学会

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