Education 【 display / non-display 】

Education 【 display / non-display 】

• 2010

  -

  2013

  Sapporo Medical University   Graduate School of Medicine   博士課程  

• 2002

  -

  2008

  Sapporo Medical University   School of Medicine   医学科  

Degree 【 display / non-display 】

Degree 【 display / non-display 】

• 2013.03   Sapporo Medical University   PhD (Medicine)

• 2008.03   Sapporo Medical University   MD

Research Experience 【 display / non-display 】

Research Experience 【 display / non-display 】

• 2025.03

  -

  Now

  Sapporo Medical University   Department of Pathology   Associate Professor

• 2019.07

  -

  2025.02

  Fukushima Medical University   Department of Pathology   Associate Professor

• 2016.08

  -

  2019.06

  Fukushima Medical University   Department of Pathology   Assistant Professor/Acting Associate Professor

• 2015.04

  -

  2016.07

  JSPS   Research Fellow in Abroad

• 2013.04

  -

  2016.07

  Victor Chang Cardiac Research Institute   Cardiac Regeneration Lab   Postdoctoral Scientist

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Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Human pathology   Cancer Biomarkers

• Life sciences   Experimental pathology   Molecular and Cellular Pathology

• Life sciences   Developmental biology   Stem Cell Biology

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University   Department of Pathology   Associate Professor  

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

• Cancer

• Epithelial Differentiation

• Genome Editing

• Tissue Regeneration

• Stem Cell

Papers 【 display / non-display 】

Papers 【 display / non-display 】

• Abnormal phosphorylation of human LRH1 at Ser510 predicts poor prognosis and promotes cell viability in lung squamous cell carcinoma.

  Hayato Mine, Kotaro Sugimoto, Makoto Kobayashi, Hironori Takagi, Naoyuki Okabe, Satoshi Muto, Yasuyuki Kobayashi, Yuko Hashimoto, Hiroyuki Suzuki, Hideki Chiba

  BMC cancer   25 ( 1 ) 764 - 764  2025.04  [International journal]

  Authorship：   Lead author  , Corresponding author

  　View Summary

  The nuclear receptor liver receptor homolog 1 (LRH1)/NR5A2 is aberrantly expressed in diverse cancer types, including liver and lung cancers. Since we previously showed that excessive phosphorylation of human LRH1 at S510 (hLRH1pS510-high) is predictable of hepatocellular carcinoma recurrence, we here clarified the clinicopathological and biological significance of hLRH1pS510-high in lung cancer. By immunohistochemistry using an anti-hLRH1pS510 monoclonal antibody, we evaluated the hLRH1pS510 signals in 151 and 150 cases of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues, respectively, and performed clinicopathological analysis. hLRH1pS510 was localized in the nucleus of tumor cells in LUAD and LUSC tissues with different intensity and proportions among the patients. Of note, the strong hLRH1pS510 signal was occasionally detectable in LUAD and LUSC cells at the expanding tumor edges. A semi-quantitative analysis revealed that 28 (18.4%) and 36 (24.0%) of LUAD and LUSC cases, respectively, exhibited hLRH1pS510-high. Kaplan-Meier plots showed significant differences in the disease-free survival (DFS) between the hLRH1pS510-high and hLRH1pS510-low groups in LUSC, but not in LUAD patients. hLRH1pS510-high was also significantly correlated with recurrence in LUSC patients. Additionally, by multivariate analysis, hLRH1pS510-high represented an independent biomarker for the DFS of LUSC patients. Furthermore, the impact of hLRH1pS510 on the viability of LUSC cells was evaluated by comparing phenotypes among two distinct LUSC cell lines expressing wild-type LRH1, LRH1S510A, and LRH1S510E. Consequently, we demonstrated that phosphorylation of hLRH1S510 accelerates the viability of LUSC cells. Thus, hLRH1pS510 is attractive not only as the predictive biomarker for LUSC but also as the potential therapeutic target.

  DOI PubMed

• Extrajunctional CLDN10 cooperates with LAT1 and accelerates clear cell renal cell carcinoma progression.

  Akifumi Onagi, Kotaro Sugimoto, Makoto Kobayashi, Yumi Sato, Yasuyuki Kobayashi, Kei Yaginuma, Satoru Meguro, Seiji Hoshi, Jyunya Hata, Yuko Hashimoto, Yoshiyuki Kojima, Hideki Chiba

  Cell communication and signaling : CCS   22 ( 1 ) 588 - 588  2024.12  [Refereed]  [International journal]

  Authorship：   Lead author  , Corresponding author

  　View Summary

  BACKGROUND & AIMS: In addition to their adhesive properties, cell adhesion molecules such as claudins (CLDNs) exhibit signaling ability to organize diverse cellular events. Although the CLDN-adhesion signaling stimulates or inhibits cancer progression, the underlying mechanism remains poorly established. Here, we verified whether and how CLDN10 promotes intracellular signals and malignant phenotypes in clear cell renal cell carcinoma (ccRCC). METHODS: We developed a novel monoclonal antibody that specifically recognizes CLDN10. By immunohistochemistry using this antibody, the clinicopathological significance of aberrant CLDN10 expression in 165 ccRCC patients was determined. We next generated the ccRCC cells (786-O, ACHN, and OS-RC-2) expressing CLDN10, and compared their phenotypes with those of control cells. Immunoprecipitation-mass spectrometry was used to identify a CLDN10-interacting protein, followed by evaluation of its association with CLDN10 and loss-of-functions in ccRCC cells. RESULTS: High CLDN10 expression predicted poor outcome in ccRCC patients and represented an independent prognostic marker for cancer-specific survival. Cell surface CLDN10 promoted cell viability, proliferation, and migration of ccRCC cells, as well as their tumor growth. CLDN10 also activated mTOR signaling and expression of downstream targets, including MYC target genes. Notably, we found that CLDN10 forms a complex with an amino acid transporter, LAT1, and that CLDN10-LAT1 signaling facilitates malignant phenotypes in ccRCC cells. Structural prediction and immunoprecipitation analysis results strongly suggest an interaction between CLDN10-TM1 (transmembrane domain 1) and LAT1-TM4. CONCLUSIONS: We conclude that CLDN10-LAT1 signaling drives ccRCC progression. Taken together with our previous findings on CLDN-Src-family kinases signaling, CLDNs propagate distinct intracellular signals depending on their association with different binding partners.

  DOI PubMed

• Comparison of clinical findings and subjective symptoms in a case of multiple evanescent white dot syndrome (MEWDS): A case report from a patient's perspective

  Kotaro Sugimoto, Toshiki Murakami, Akira Ojima, Tetsuju Sekiryu

  Journal of General and Family Medicine    2024.05

  Authorship：   Lead author  , Corresponding author

  DOI

• The Src-Family Kinases SRC and BLK Contribute to the CLDN6-Adhesion Signaling.

  Naoki Ichikawa-Tomikawa, Kotaro Sugimoto, Korehito Kashiwagi, Hideki Chiba

  Cells   12 ( 13 )  2023.06  [Refereed]  [Invited]  [International journal]

  Authorship：   Lead author

  　View Summary

  Cell adhesion molecules, including integrins, cadherins, and claudins (CLDNs), are known to activate Src-family kinases (SFKs) that organize a variety of physiological and pathological processes; however, the underlying molecular basis remains unclear. Here, we identify the SFK members that are coupled with the CLDN6-adhesion signaling. Among SFK subtypes, BLK, FGR, HCK, and SRC were highly expressed in F9 cells and concentrated with CLDN6 along cell borders during epithelial differentiation. Immunoprecipitation assay showed that BLK and SRC, but not FGR or HCK, form a complex with CLDN6 via the C-terminal cytoplasmic domain. We also demonstrated, by pull-down assay, that recombinant BLK and SRC proteins directly bind to the C-terminal cytoplasmic domain of CLDN6 (CLDN6C). Unexpectedly, both recombinant SFK proteins recognized the CLDN6C peptide in a phosphotyrosine-independent manner. Furthermore, by comparing phenotypes of F9:Cldn6:Blk-/- and F9:Cldn6:Src-/- cells with those of wild-type F9 and F9:Cldn6 cells, we revealed that BLK and SRC are essential for CLDN6-triggered cellular events, namely epithelial differentiation and the expression of retinoid acid receptor target genes. These results indicate that selective SFK members appear to participate in the CLDN-adhesion signaling.

  DOI PubMed

• Aberrant phosphorylation of human LRH1 at serine 510 is predictable of hepatocellular carcinoma recurrence.

  Atsushi Nishimagi, Makoto Kobayashi, Kotaro Sugimoto, Yasuhide Kofunato, Naoya Sato, Junichiro Haga, Teruhide Ishigame, Takashi Kimura, Akira Kenjo, Yasuyuki Kobayashi, Yuko Hashimoto, Shigeru Marubashi, Hideki Chiba

  Clinical and experimental medicine    2023.06  [Refereed]  [International journal]

  Authorship：   Corresponding author

  　View Summary

  We previously identified the AKT-phosphorylation sites in nuclear receptors and showed that phosphorylation of S379 in mouse retinoic acid γ and S518 in human estrogen receptor α regulate their activity independently of the ligands. Since this site is conserved at S510 in human liver receptor homolog 1 (hLRH1), we developed a monoclonal antibody (mAb) that recognized the phosphorylation form of hLRH1S510 (hLRH1pS510) and verified its clinicopathological significance in hepatocellular carcinoma (HCC). We generated the anti-hLRH1pS510 mAb and assessed its selectivity. We then evaluated the hLRH1pS510 signals in 157 cases of HCC tissues by immunohistochemistry because LRH1 contributes to the pathogenesis of diverse cancers. The developed mAb specifically recognized hLRH1pS510 and worked for immunohistochemistry of formalin-fixed paraffin-embedded tissues. hLRH1pS510 was exclusively localized in the nucleus of HCC cells, but the signal intensity and positive rates varied among the subjects. According to the semi-quantification, 45 cases (34.9%) showed hLRH1pS510-high, and the remaining 112 cases (65.1%) exhibited hLRH1pS510-low. There were significant differences in the recurrence-free survival (RFS) between the two groups, and the 5-year RFS rates in the hLRH1pS510-high and hLRH1pS510-low groups were 26.5% and 46.1%, respectively. In addition, high hLRH1pS510 was significantly correlated with portal vein invasion, hepatic vein invasion, and high levels of serum alpha-fetoprotein (AFP). Furthermore, multivariable analysis revealed that hLRH1pS510-high was an independent biomarker for HCC recurrence. We conclude that aberrant phosphorylation of hLRH1S510 is a predictor of poor prognosis for HCC. The anti-hLRH1pS510 mAb could provide a powerful tool to validate the relevance of hLRH1pS510 in pathological processes such as tumor development and progression.

  DOI PubMed

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• 核内受容体の新規調節機構の発見と病理学への展開

  杉本 幸太郎, 千葉 英樹

  福島医学雑誌 ( 福島医学会 )  73 ( 3 ) 65 - 71  2023.12

  　View Summary

  要旨:核内受容体は様々な脂質を天然リガンドとする転写因子で,ヒトではレチノイン酸受容体,ビタミンD受容体,性ホルモン受容体,副腎皮質ホルモン受容体,および甲状腺ホルモン受容体など48種類が同定されている。核内受容体の転写活性は,基本的には特異リガンドとの結合によって調節されているが,実際にはリン酸化などの翻訳後修飾も影響する。我々は最近,細胞間接着から核内受容体のセリンリン酸化に至る新規のシグナル伝達経路を発見し,これが幹細胞分化および子宮体癌と乳癌の悪性形質増強に寄与することを明らかにした。本総説ではその一連の研究を紹介する。(著者抄録)

• 臨床検体を用いたバイオマーカー研究 Auto-immunomicsを基盤としたがん患者血清中自己抗体の網羅的探索

  小林 信, 片山 博之, 杉本 幸太郎, 千葉 英樹

  電気泳動 ( 日本電気泳動学会 )  65 ( Suppl. ) s7 - s7  2021.07

• 新規のエストロゲン受容体活性化機構とがんの細胞制御

  杉本 幸太郎

  上原記念生命科学財団研究報告集 ( (公財)上原記念生命科学財団 )  34   1 - 4  2020.12

• 術中迅速細胞診で診断困難であった脳腫瘍の1例

  平野 響子, 黒田 和希, 小林 英樹, 杉本 幸太郎

  日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 )  63 ( Suppl.2 ) 640 - 640  2024.10

• 核内受容体の新規調節機構の発見と疾患への展開(The tight junction-nuclear receptor signalling pathway in physiological and pathological states)

  杉本 幸太郎

  日本病理学会会誌 ( (一社)日本病理学会 )  113 ( 2 ) 81 - 81  2024.10

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Industrial Property Rights 【 display / non-display 】

Industrial Property Rights 【 display / non-display 】

• 子宮体癌患者の予後予測バイオマーカー

  特許第7374499号

  千葉 英樹, 杉本 幸太郎

  Patent

  J-GLOBAL

• 卵巣がん患者の予後予測用バイオマーカー

  小林 信, 杉本 幸太郎, 千葉 英樹

  Patent

  J-GLOBAL

• 女性ホルモン依存性がんの悪性度及び予後の判定のためのバイオマーカー

  千葉 英樹, 杉本 幸太郎

  Patent

  J-GLOBAL

• 細胞培養補助剤

  千葉 英樹, 杉本 幸太郎

  Patent

  J-GLOBAL

• 子宮体癌患者の予後予測バイオマーカー

  千葉 英樹, 杉本 幸太郎

  Patent

  J-GLOBAL

Awards 【 display / non-display 】

Awards 【 display / non-display 】

• JSPS Research Award

  2024   日本病理学会  

  Winner： Kotaro Sugimoto

• Young Investigator Award

  2021   The Japanese Society for Pathology  

  Winner： Kotaro Sugimoto

• Rookie Award

  2013   The Japanese Society of Pathology  

  Winner： Kotaro SUGIMOTO

• Teacher of the year

  2023   Fukushima Medical University  

  Winner： Sugimoto Kotaro

• Young investigator award

  2022   Fukushima Society of Medical Science  

  Winner： Kotaro Sugimoto

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Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• SPON1 is a novel prognostic biomarker for ovarian cancer.

  Project Year :

  2023.04

  -

  2025.03

   

  Authorship： Principal investigator

• Forward genetic identification of new players in vitamin D signaling.

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2021.04

  -

  2024.03

   

  杉本 幸太郎

  　View Summary

  ビタミンDシグナルは骨代謝のみならず腫瘍発生など様々な生命現象に関与している。同シグナルの作用は主にビタミンD受容体(VDR)など核内受容体(NR)に属する転写因子を介した下流標的遺伝子の転写制御である。NRは特異リガンドのみならず様々な内因性蛋白質によって活性が調節されているが、これまでの創薬研究はリガンドの同定や新規合成に偏っており、内因性蛋白質を対象とするものは少ない。最近我々は最近細胞接着を基点とする一連のシグナルカスケードが、NRのセリン・リン酸化を介してリガンド感受性を著しく亢進させることを報告した。これはキナーゼを標的としてビタミンDシグナルを制御するという新たな治療戦略の可能性を示唆する。そこで本研究では順遺伝学的アプローチによりビタミンDシグナル関連蛋白質を網羅的に同定しようと試みた。まずビタミンDシグナルの蛍光レポーターを恒常発現する細胞株を樹立し、次に全遺伝子に対すプール化されたCRISPR-gRNA発現ベクターを導入する。これらの細胞にビタミンDを低濃度と高濃度で処理し、セルソーターで蛍光強度を測定する。低用量のビタミンDでレポーター活性の高いものを抽出すれば、これにはビタミンDシグナルを負に制御する遺伝子群を機能欠失した細胞群が含まれているはずで、逆もまた真である。この細胞群からゲノミックDNAを回収し取り込まれたsgRNA配列を次世代シークエンシングによって解析することで、ビタミンDシグナルを正負に制御する遺伝子群を網羅的に同定する。以上の研究計画のうち、本研究期間では上記のうちレポーター系の構築、選定、ならびに最適化を実施した。またgRNAライブラリの準備とトランスフェクションの最適化を完了している。

• Forward genetic analysis to identify novel players in the retioic acid signalling pathway.

  Project Year :

  2021.04

  -

  2022.03

   

  Kotaro Sugimoto

  Authorship： Principal investigator

• Claudin-Nuclear receptor-axis in breast cancer.

  Project Year :

  2020.10

  -

  2022.03

   

  Kotaro Sugimoto

  Authorship： Principal investigator

• Forward genetic analysis to identify novel cancer drivers in the retioic acid signalling pathway.

  Project Year :

  2020.10

  -

  2021.09

   

  Kotaro Sugimoto

  Authorship： Principal investigator

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Presentations 【 display / non-display 】

Presentations 【 display / non-display 】

• The tight junction-nuclear receptor signalling pathway in physiological and pathological states.

  Kotaro Sugimoto  [Invited]

  70th JSPS Annual Meeting 

  Presentation date： 2024.11

  Event date：

  2024.11

  　

  　

• 臨床検体を用いたバイオマーカー研究 細胞接着分子クローディンとがん マーカー分子としての有用性と治療標的としての可能性

  杉本 幸太郎, 小林 信, 千葉 英樹

  電気泳動  日本電気泳動学会

  Presentation date： 2021.07

  Event date：

  2021.07

  　

  　

• 多機能な細胞接着分子が関わるがんの理解 診断・治療への応用をめざして 細胞接着シグナルによる正常細胞機能とがん悪性形質の新規制御機構

  杉本 幸太郎, 冨川 直樹, 柏木 維人, 小島 学, 村上 祐子, 田中 瑞子, 東 智仁, 千葉 英樹

  日本病理学会会誌  (一社)日本病理学会

  Presentation date： 2018.04

  Event date：

  2018.04

  　

  　

• 細胞性免疫主体の障害が病理で示された、肺小細胞癌に伴う抗NMDA受容体脳炎の72歳女性例

  赤沼 春菜, 吉田 健二, 阿部 暖, 松田 希, 金井 数明, 杉本 幸太郎, 橋本 優子, 飯塚 高浩

  臨床神経学  (一社)日本神経学会

  Presentation date： 2022.05

  Event date：

  2022.05

  　

  　

• 卵巣癌に起因する細胞表面タンパク質シグネチャーの同定

  小林 信, 杉本 幸太郎, 遠藤 雄大, 宮川 諒也, 瓜生 開, 田口 歩, 千葉 英樹

  日本病理学会会誌  (一社)日本病理学会

  Presentation date： 2022.03

  Event date：

  2022.03

  　

  　

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Teaching Experience 【 display / non-display 】

Teaching Experience 【 display / non-display 】

• Pathology (pancreas and biliary system)  

  Sapporo Medical University  

  2025

  -

  Now

   

• Pathology (aging and senescence)  

  Sapporo Medical University  

  2024

  -

  Now

   

• Neuropathology  

  Fukushima Medical University  

  2022.04

  -

  Now

   

• Cardiovascular Pathology  

  Fukushima Medical University  

  2018

  -

  Now

   

• Tumours of the Urinary System and Male Genital Organs  

  Fukushima Medical University  

  2017.07

  -

  Now

   

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