Education 【 display / non-display 】

Education 【 display / non-display 】

• 2017

  -

  2020

  Sapporo Medical University   Graduate School of Medicine  

• 2009

  -

  2015

  Sapporo Medical University   School of Medicine  

Research Experience 【 display / non-display 】

Research Experience 【 display / non-display 】

• 2024.02

  -

  Now

  Sapporo Medical University   Department of Cell Science, Cancer Research Institute   Assistant Professor

• 2023.03

  -

  2024.01

  Sapporo Medical University   Department of Cell Science, Research Institute for Frontier Medicine   Postdoctoral fellow

• 2021.01

  -

  2023.01

  Massachusetts General Hospital   Department of Pediatrics, Mucosal Immunology and Biology Research Center   Postdoctoral fellow

• 2020.04

  -

  2020.12

  Sapporo Medical University   School of Medicine   Postdoctoral fellow

• 2018.04

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  2020.03

  Japan Society for the Promotion of Science   Research fellow

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Institute of Cancer Research, School of Medicine, Sapporo Medical University   Department of Cell Science   Assistant Professor  

Papers 【 display / non-display 】

Papers 【 display / non-display 】

• The roles of tight junction protein cingulin in human endometrioid endometrial cancer.

  Arisa Kura, Kimihito Saito, Takumi Konno, Takayuki Kohno, Hiroshi Shimada, Tadahi Okada, Soshi Nishida, Daichi Ishii, Motoki Matsuura, Tsuyoshi Saito, Takashi Kojima

  Tissue barriers     2361976 - 2361976  2024.06  [International journal]

  　View Summary

  The bicellular tight junction molecule cingulin (CGN) binds to microtubules in centrosomes. Furthermore, CGN contributes to the tricellular tight junction (tTJ) proteins lipolysis-stimulated lipoprotein receptor (LSR) and tricellulin (TRIC). CGN as well as LSR decreased during the malignancy of endometrioid endometrial cancer (EEC). Although tTJ protein LSR is involved in the malignancy of some cancers, including EEC, the role of CGN is unknown. In this study, we investigated the roles of CGN with tTJ proteins in human EEC cells by using the CGN-overexpressing EEC cell line Sawano. In 2D cultures, CGN was colocalized with LSR and TRIC at tTJ or at γ-tubulin-positive centrosomes. In immunoprecipitation with CGN antibodies, CGN directly bound to LSR, TRIC, and β-tubulin. Knockdown of CGN by the siRNA decreased the epithelial barrier and enhanced cell proliferation, migration and invasion, as well as knockdown of LSR. In the Sawano cells cocultured with normal human endometrial stromal cells, knockdown of CGN decreased expression of LSR and TRIC via MAPK and AMPK pathways. In 2.5D cultures, knockdown of CGN induced the formation of abnormal cysts and increased the permeability of FD-4 to the lumen. In 2D and 2.5D cultures, treatment with β-estradiol with or without EGF or TGF-β decreased CGN expression and the epithelial permeability barrier and enhanced cell migration, and pretreatment with EW7197+AG1478, U0126 or an anti-IL-6 antibody prevented this. In conclusion, CGN, with tTJ proteins might suppress the malignancy of human EEC and its complex proteins are sensitive to estrogen and growth factors derived from stromal cells.

  DOI PubMed

• Gap junction beta-4 accelerates cell cycle progression and metastasis through MET-AKT activation in pancreatic cancer.

  Joji Muramatsu, Yohei Arihara, Makoto Yoshida, Tomohiro Kubo, Hajime Nakamura, Kazuma Ishikawa, Hiromi Fujita, Shintaro Sugita, Takumi Konno, Takashi Kojima, Yutaka Kawano, Masayoshi Kobune, Kohichi Takada

  Cancer science   115 ( 5 ) 1564 - 1575  2024.05  [International journal]

  　View Summary

  Despite continuing advances in the development of effective new therapies, including immunotherapies, the prognosis of pancreatic cancer remains extremely poor. Gap junction proteins have become attractive targets for potential cancer therapy. However, the role of gap junction beta-4 (GJB4) protein remains unexplored in pancreatic cancer. Through bioinformatic analyses we discovered pancreatic cancer tissues showed higher levels of GJB4 transcripts compared to normal pancreatic tissues and this had a negative effect on overall survival in patients that had pancreatic cancer. The high expression of nuclear GJB4 was identified as a negative prognostic factor in such patients. Knockdown of GJB4 in cultured pancreatic cancer cells resulted in G0/G1 arrest followed by decreased cell proliferation and suppression of metastatic potential. The overexpression of GJB4 accelerated cell proliferation, migration, and invasion in a SUIT-2 cell line, whereas MET inhibitor canceled the acceleration. GJB4 suppression with siRNA significantly inhibited tumor growth in a mouse xenograft model. Mechanistically, suppression of GJB4 inhibited MET-AKT activities. Such data suggest that targeting the GJB4-MET axis could represent a promising new therapeutic strategy for pancreatic cancer.

  DOI PubMed

• The Roles and Regulatory Mechanisms of Tight Junction Protein Cingulin and Transcription Factor Forkhead Box Protein O1 in Human Lung Adenocarcinoma A549 Cells and Normal Lung Epithelial Cells.

  Daichi Ishii, Yuma Shindo, Wataru Arai, Takumi Konno, Takayuki Kohno, Kazuya Honda, Masahiro Miyajima, Atsushi Watanabe, Takashi Kojima

  International journal of molecular sciences   25 ( 3 )  2024.01  [International journal]

  　View Summary

  Tight junction (TJ) protein cingulin (CGN) and transcription factor forkhead box protein O1 (FOXO1) contribute to the development of various cancers. Histone deacetylase (HDAC) inhibitors have a potential therapeutic role for some cancers. HDAC inhibitors affect the expression of both CGN and FOXO1. However, the roles and regulatory mechanisms of CGN and FOXO1 are unknown in non-small cell lung cancer (NSCLC) and normal human lung epithelial (HLE) cells. In the present study, to investigate the effects of CGN and FOXO1 on the malignancy of NSCLC, we used A549 cells as human lung adenocarcinoma and primary human lung epithelial (HLE) cells as normal lung tissues and performed the knockdown of CGN and FOXO1 by siRNAs. Furthermore, to investigate the detailed mechanisms in the antitumor effects of HDAC inhibitors for NSCLC via CGN and FOXO1, A549 cells and HLE cells were treated with the HDAC inhibitors trichostatin A (TSA) and Quisinostat (JNJ-2648158). In A549 cells, the knockdown of CGN increased bicellular TJ protein claudin-2 (CLDN-2) via mitogen-activated protein kinase/adenosine monophosphate-activated protein kinase (MAPK/AMPK) pathways and induced cell migration, while the knockdown of FOXO1 increased claudin-4 (CLDN-4), decreased CGN, and induced cell proliferation. The knockdown of CGN and FOXO1 induced cell metabolism in A549 cells. TSA and Quisinostat increased CGN and tricellular TJ protein angulin-1/lipolysis-stimulated lipoprotein receptor (LSR) in A549. In normal HLE cells, the knockdown of CGN and FOXO1 increased CLDN-4, while HDAC inhibitors increased CGN and CLDN-4. In conclusion, the knockdown of CGN via FOXO1 contributes to the malignancy of NSCLC. Both HDAC inhibitors, TSA and Quisinostat, may have potential for use in therapy for lung adenocarcinoma via changes in the expression of CGN and FOXO1.

  DOI PubMed

• The interplay between the epithelial permeability barrier, cell migration and mitochondrial metabolism of growth factors and their inhibitors in a human endometrial carcinoma cell line.

  Takumi Konno, Takayuki Kohno, Shin Kikuchi, Arisa Kura, Kimihito Saito, Tadahi Okada, Hiroshi Shimada, Yuya Yamazaki, Tomoki Sugiyama, Motoki Matsuura, Yuki Ohsaki, Tsuyoshi Saito, Takashi Kojima

  Tissue barriers     2304443 - 2304443  2024.01  [International journal]

  　View Summary

  It is known that there are abnormalities of tight junction functions, cell migration and mitochondrial metabolism in human endometriosis and endometrial carcinoma. In this study, we investigated the effects of growth factors and their inhibitors on the epithelial permeability barrier, cell migration and mitochondrial metabolism in 2D and 2.5D cultures of human endometrioid endometrial carcinoma Sawano cells. We also investigated the changes of bicellular and tricellular tight junction molecules and ciliogenesis induced by these inhibitors. The growth factors TGF-β and EGF affected the epithelial permeability barrier, cell migration and expression of bicellular and tricellular tight junction molecules in 2D and 2.5D cultures of Sawano cells. EW-7197 (a TGF-β receptor inhibitor), AG1478 (an EGFR inhibitor) and SP600125 (a JNK inhibitor) affected the epithelial permeability barrier, cell migration and mitochondrial metabolism and prevented the changes induced by TGF-β and EGF in 2D and 2.5D cultures. EW-7197 and AG1478 induced ciliogenesis in 2.5D cultures. In conclusion, TGF-β and EGF promoted the malignancy of endometrial cancer via interplay among the epithelial permeability barrier, cell migration and mitochondrial metabolism. EW-7197 and AG1478 may be useful as novel therapeutic treatments options for endometrial cancer.

  DOI PubMed

• Evaluating Prophylactic Effect of Bovine Colostrum on Intestinal Barrier Function in Zonulin Transgenic Mice: A Transcriptomic Study.

  Birna Asbjornsdottir, Snaevar Sigurdsson, Alba Miranda-Ribera, Maria Fiorentino, Takumi Konno, Jinggang Lan, Larus S Gudmundsson, Magnus Gottfredsson, Bertrand Lauth, Bryndis Eva Birgisdottir, Alessio Fasano

  International journal of molecular sciences ( MDPI AG )  24 ( 19 ) 14730 - 14730  2023.09  [International journal]

  　View Summary

  The intestinal barrier comprises a single layer of epithelial cells tightly joined to form a physical barrier. Disruption or compromise of the intestinal barrier can lead to the inadvertent activation of immune cells, potentially causing an increased risk of chronic inflammation in various tissues. Recent research has suggested that specific dietary components may influence the function of the intestinal barrier, potentially offering a means to prevent or mitigate inflammatory disorders. However, the precise mechanism underlying these effects remains unclear. Bovine colostrum (BC), the first milk from cows after calving, is a natural source of nutrients with immunomodulatory, anti-inflammatory, and gut-barrier fortifying properties. This novel study sought to investigate the transcriptome in BC-treated Zonulin transgenic mice (Ztm), characterized by dysbiotic microbiota, intestinal hyperpermeability, and mild hyperactivity, applying RNA sequencing. Seventy-five tissue samples from the duodenum, colon, and brain of Ztm and wild-type (WT) mice were dissected, processed, and RNA sequenced. The expression profiles were analyzed and integrated to identify differentially expressed genes (DEGs) and differentially expressed transcripts (DETs). These were then further examined using bioinformatics tools. RNA-seq analysis identified 1298 DEGs and 20,952 DETs in the paired (Ztm treatment vs. Ztm control) and reference (WT controls) groups. Of these, 733 DEGs and 10,476 DETs were upregulated, while 565 DEGs and 6097 DETs were downregulated. BC-treated Ztm female mice showed significant upregulation of cingulin (Cgn) and claudin 12 (Cldn12) duodenum and protein interactions, as well as molecular pathways and interactions pertaining to tight junctions, while BC-treated Ztm males displayed an upregulation of transcripts like occludin (Ocln) and Rho/Rac guanine nucleotide exchange factor 2 (Arhgf2) and cellular structures and interfaces, protein–protein interactions, and organization and response mechanisms. This comprehensive analysis reveals the influence of BC treatment on tight junctions (TJs) and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling pathway gene expressions. The present study is the first to analyze intestinal and brain samples from BC-treated Ztm mice applying high-throughput RNA sequencing. This study revealed molecular interaction in intestinal barrier function and identified hub genes and their functional pathways and biological processes in response to BC treatment in Ztm mice. Further research is needed to validate these findings and explore their implications for dietary interventions aimed at improving intestinal barrier integrity and function. The MGH Institutional Animal Care and Use Committee authorized the animal study (2013N000013).

  DOI PubMed

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• ヒト子宮内膜症のin vitroモデルを用いた新規病態メカニズムの解明

  長尾来夢, 長尾来夢, 幸野貴之, 金野匠, 倉ありさ, 倉ありさ, 斉藤公仁, 嶋田浩志, 齋藤豪, 小島隆

  日本臨床分子形態学会総会・学術集会講演プログラム・要旨集   55th  2023

  J-GLOBAL

• 子宮内膜癌におけるタイト結合分子cingulin(CGN)の役割

  倉ありさ, 倉ありさ, 斉藤公仁, 斉藤公仁, 岡田匡氷, 嶋田浩志, 金野匠, 幸野貴之, 松浦基樹, 齋藤豪, 小島隆

  日本臨床分子形態学会総会・学術集会講演プログラム・要旨集   54th  2022

  J-GLOBAL

• 子宮内膜症,子宮内膜癌細胞におけるAngulin-1/Lipolysis Stimulated Lipoprotein Receptor(LSR)の役割

  斉藤公仁, 斉藤公仁, 嶋田浩志, 金野匠, 倉ありさ, 倉ありさ, 岡田匡氷, 郷久晴朗, 幸野貴之, 松浦基樹, 齋藤豪, 小島隆

  日本臨床分子形態学会総会・学術集会講演プログラム・要旨集   54th  2022

  J-GLOBAL

• Possibility of tricelluler tight junction LSR/Angulin-1 antibody in therapy for human endometrioid endometrial carcinoma

  斉藤公仁, 幸野貴之, 金野匠, 岡田匡氷, 嶋田浩志, 郷久晴朗, 近藤昌夫, 齋藤豪, 小島隆

  日本分子生物学会年会プログラム・要旨集(Web)   44th  2021

  J-GLOBAL

• 子宮内膜症のin vitroモデルを用いた病態メカニズムの解明

  嶋田浩志, 岡田匡氷, 金野匠, 郷久晴朗, 幸野貴之, 小島隆, 齋藤豪

  日本エンドメトリオーシス学会プログラム・抄録集   41st  2020

  J-GLOBAL

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Awards 【 display / non-display 】

Awards 【 display / non-display 】

• Travel Grants for Cell Bio 2023 attendees

  2023.12   The American Society for Cell Biology  

• 奨励金

  2019.02   公益信託岩澤ゑい癌研究助成基金  

• 研修医奨励賞

  2016.09   日本消化器病学会北海道支部   インフリキシマブにより維持治療されたクローン病における長期手術率に関する検討

Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• 炎症関連タンパク質HMGB1を介した大腸肺連関における上皮透過性異常の病態メカニズム解明とその治療応用

  Project Year :

  2024.09

  -

  2025.03

   

  Authorship： Principal investigator

• Investigation of the potential of zonulin inhibitors as a novel therapeutic agent for Crohn's Disease

  Grant-in-Aid for Early-Career Scientists

  Project Year :

  2024.04

  -

  2027.03

   

  金野 匠

• 上皮バリア機能低下におけるAT-1001の役割

  Project Year :

  2023.12

  　

  　

   

  Authorship： Principal investigator

• Zonulin依存性の腸管バリア調節メカニズムの解析

  Project Year :

  2021.01

  -

  2023.01

   

  Authorship： Principal investigator

• 自己免疫疾患における腸管バリア機能の解析

  Project Year :

  2021.01

  -

  2023.01

   

  Authorship： Principal investigator

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