Development of personalized medcicine for inflammatory bowel disease based on control of epigenome
Project/Area Number |
18H02799
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 53010:Gastroenterology-related
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Research Institution | Sapporo Medical University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
青井 貴之 神戸大学, 科学技術イノベーション研究科, 教授 (00546997)
鈴木 拓 札幌医科大学, 医学部, 教授 (20381254)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2020: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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Keywords | iPS細胞 / オルガノイド / 腸管上皮細胞 / エピゲノム / 自然免疫 / 炎症性腸疾患 / メチル化 / IPS細胞 |
Outline of Final Research Achievements |
In the present study, we have established organoids from intestinal epithelial cells of UC patients. We have succeeded in iPS conversion of intestinal organoids and differentiation of the cells into intestinal epithelium. We extracted DNA from the organoids of patients and the differentiated intestinal epithelial cells that originated from iPS and comprehensively analyzed the epigenomic changes. We found that epigenomic changes in transcription factors related to intestinal epithelial cell differentiation regulation.
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Academic Significance and Societal Importance of the Research Achievements |
炎症性腸疾患(IBD)は再発再燃を繰り返す原因不明の難治性疾患であるが、その発症原因は現在のところ明らかとなってはいない。本邦における患者数は増加の一途を辿り、根本的治療方法の開発が望まれている。遺伝的要因のみならず、後天的細胞機能異常がIBD発症に関与している可能性が強く示唆されている。我々は、日本人IBD患者の腸管上皮細胞からiPS細胞を樹立し、iPS細胞からさらに分化誘導された腸管上皮細胞を含む自然免疫担当細胞を用いることにより、個々の患者のエピゲノム変化をとらえるシステムを構築した。今後は、この手法を用いてIBD患者一人一人の細胞機能異常が同定し、究極の個別医療を開発につなげていく。
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Report
(4 results)
Research Products
(52 results)
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[Journal Article] Adrenomedullin for steroid-resistant ulcerative colitis: a randomized, double-blind, placebo-controlled phase-2a clinical trial.2021
Author(s)
Kita T, Ashizuka S, Ohmiya N, Yamamoto T, Kanai T, Motoya S, Hirai F, Nakase H, Moriyama T, Nakamura M, Suzuki Y, Kanmura S, Kobayashi T, Ohi H, Nozaki R, Mitsuyama K, Yamamoto S, Inatsu H, Watanabe K, Hibi T, Kitamura K.
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Journal Title
J Gastroenterol
Volume: 56
Issue: 2
Pages: 147-157
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Intestinal cancer in patients with Crohn's disease: A systematic review and meta-analysis2021
Author(s)
Motoi Uchino, Hiroki Ikeuchi, Keisuke Hata, Tomohiro Minagawa, Yuki Horio, Ryuichi Kuwahara, Shiro Nakamura, Kenji Watanabe, Masayuki Saruta, Toshimitsu Fujii, Taku Kobayashi, Ken Sugimoto, Fumihito Hirai, Motohiro Esaki, Sakiko Hiraoka, Katsuyoshi Matsuoka, Shinichiro Shinzaki, Minoru Matsuura, Nagamu Inoue, et al
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Journal Title
J Gastroenterol Hepatol
Volume: 36
Issue: 2
Pages: 329-336
DOI
Related Report
Peer Reviewed
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[Journal Article] Does anti-tumor necrosis factor alpha prevent the recurrence of Crohn's disease? Systematic review and meta-analysis2021
Author(s)
Uchino M, Ikeuchi H, Hata K, Minagawa T, Horio Y, Kuwahara R, Nakamura S, Watanabe K, Saruta M, Fujii T, Kobayashi T, Sugimoto K, Hirai F, Esaki M, Hiraoka S, Matsuoka K, Shinzaki S, Matsuura M, Inoue N, Nakase H, Watanabe M.
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Journal Title
J Gastroenterol Hepatol
Volume: -
Issue: 4
Pages: 864-872
DOI
Related Report
Peer Reviewed
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[Journal Article] Genetic Background of Mesalamine-induced Fever and Diarrhea in Japanese Patients with Inflammatory Bowel Disease2021
Author(s)
Suzuki K, Kakuta Y, Naito T, Takagawa T, Hanai H, Araki H, Sasaki Y, Sakuraba H, Sasaki M, Hisamatsu T, Motoya S, Matsumoto T, Onodera M, Ishiguro Y, Nakase H, et al.
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Journal Title
Inflamm Bowel Dis
Volume: -
Issue: 1
Pages: 21-31
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Long-term follow-up of targeted biopsy yield (LOFTY Study) in ulcerative colitis surveillance colonoscopy.2020
Author(s)
Hata K, Ishihara S, Ajioka Y, Mitsuyama K, Watanabe K, Hanai H, Kunisaki R, Nakase H, Matsuda K, Iwakiri R, Hida N, Tanaka S, Takeuchi Y, Shinozaki M, Ogata N, Moriichi K, Hirai F, Sugihara K, Hisamatsu T, Suzuki Y, Watanabe M, Hibi T.
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Journal Title
J Clin Med
Volume: 18
Issue: 7
Pages: 2286-2286
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Expert opinions on the current therapeutic management of inflammatory bowel disease during the COVID-19 pandemic: Japan IBD COVID-19 taskforce, intractable diseases, the health and labor sciences research.2020
Author(s)
akase H, Matsumoto T, Matsuura M, Iijima H, Matsuoka K, Ohmiya N, Ishihara S, Hirai F, Wagatsuma K, Yokoyama Y, Hisamatsu T.
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Journal Title
Digestion
Volume: -
Issue: 5
Pages: 1-9
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Automatic, computer-aided determination of endoscopic and histological inflammation in patients with mild to moderate ulcerative colitis based on red density.2020
Author(s)
Bossuyt P, Nakase H, Vermeire S, de Hertogh G, Eelbode T, Ferrante M, Hasegawa T, Willekens H, Ikemoto Y, Makino T, Bisschops R.
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Journal Title
GUT
Volume: 69
Issue: 10
Pages: 1778-1786
DOI
Related Report
Peer Reviewed
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[Journal Article] Artificial intelligence-assisted endoscopy changes the definition of mucosal healing in ulcerative colitis.2020
Author(s)
Nakase H, Hirano T, Wagatsuma K, Ichimiya T, Yamakawa T, Yokoyama Y, Hayashi Y, Hirayama D, Kazama T, Yoshii S, Yamano HO.
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Journal Title
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Exploratory study of the effectiveness of granulocyte and monocyte adsorptive apheresis before initiation of steroids in patients with active ulcerative colitis (EXPECT study): A multicenter prospective clinical trial.2020
Author(s)
Kakimoto K, Matsuura M, Takumi Fukuchi, Hongo H, Kimura T, Aoyama N, Okuda Y, Aomatsu K, Kamata N, Yokoyama Y, Mizuno C, Inoue T, Miyazaki T, Nakamura S, Higuchi K, Nakase H.
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Journal Title
Crohn’s & Colitis 360.
Volume: 2
Related Report
Peer Reviewed / Open Access
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[Journal Article] Concerns and side effects of azathioprine during adalimumab induction and maintenance therapy for Japanese patients with Crohn's disease: a sub-analysis of a prospective randomized clinical trial (DIAMOND study).2019
Author(s)
Hisamatsu T, Matsumoto T, Watanabe K,;Nakase H, Motoya S, Yoshimura N, Ishida T, Kato S, Nakagawa T, Esaki M, Nagahori M, Matsui T, Naito Y, Kanai T, Suzuki Y, Nojima M, Watanabe M, Hibi T; DIAMOND study group.
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Journal Title
J Crohns Colitis.
Volume: 印刷中
Issue: 9
Pages: 1097-1104
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Clinical and Pharmacokinetic Factors Associated With Adalimumab-Induced Mucosal Healing in Patients With Crohn's Disease.2018
Author(s)
Watanabe K, Matsumoto T, Hisamatsu T, Nakase H, Motoya S, Yoshimura N, Ishida T, Kato S, Nakagawa T, Esaki M, Nagahori M, Matsui T, Naito Y, Kanai T, Suzuki Y, Nojima M, Watanabe M, Hibi T; DIAMOND study group.
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Journal Title
Clin Gastroenterol Hepatol.
Volume: 16
Issue: 4
Pages: 542-549
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Efficacy of endoscopic balloon dilation for small bowel strictures in patients with Crohn’s disease: a nationwide, multi-centre, open-label, prospective cohort study.2018
Author(s)
Hirai F, Andoh A, Ueno F, Watanabe K, Ohmiya N, Nakase H, Kato S, Esaki M, Endo Y, Yamamoto H, Matsui T, Iida M, Hibi T, Watanabe M, Suzuki Y, Matsumoto T.
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Journal Title
J Crohns Colitis.
Volume: 12
Issue: 4
Pages: 394-401
DOI
Related Report
Peer Reviewed
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[Journal Article] Evidence-based clinical practice guidelines for inflammatory bowel disease.2018
Author(s)
Matsuoka K, Kobayashi T, Ueno F, Matsui T, Hirai F, Inoue N, Kato J, Kobayashi K, Kobayashi K, Koganei K, Kunisaki R, Motoya S, Nagahori M, Nakase H, Omata F, Saruta M, Watanabe T, Tanaka T, Kanai T, Noguchi Y, Takahashi K, Watanabe K, Hibi T, Suzuki Y, Watanabe M, Sugano K, Shimosegawa T.
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Journal Title
J Gastroenterol.
Volume: 53
Issue: 3
Pages: 305-353
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] IgA regulates the composition and metabolic function of gut microbiota by promoting symbiosis between bacteria.2018
Author(s)
Nakajima A, Vogelzang A, Maruya M, Miyajima M, Murata M, Son A, Kuwahara T, Tsuruyama T, Yamada S, Matsuura M, Nakase H, Peterson DA, Fagarasan S, Suzuki K.
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Journal Title
J Exp Med.
Volume: 215
Issue: 8
Pages: 2019-2034
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Effect of elemental diet combined with infliximab dose escalation in patients with Crohn’s disease with loss of response to infliximab: CERISIER trial.2018
Author(s)
Hisamatsu T, Kunisaki R, Nakamura S, Tsujikawa T, Hirai F, Nakase H, Watanabe K, Yokoyama K, Nagahori M, Kanai T, Naganuma M, Michimae H, Andoh A, Yamada A, Yokoyama T, Kamata N, Tanaka S, Suzuki Y, Hibi T, Watanabe M.
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Journal Title
Intest Res.
Volume: 16
Issue: 3
Pages: 494-498
DOI
Related Report
Peer Reviewed / Open Access
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