KEIO RESEARCHERS INFORMATION SYSTEM

Career 【 Display / hide 】

Career 【 Display / hide 】

• 1993.04

  -

  1998.06

  National Cancer Center, Pathology Division, Research member

• 1998.07

  -

  2002.06

  National Cancer Center, Pathology Division, Head of Section

• 2002.07

  -

  2010.03

  National Cancer Center, Pathology Division, Chief

• 2010.04

  -

  2017.03

  National Cancer Center Research Institute, Division of Molecular Pathology, Chief

• 2010.11

  -

  2014.03

  National Cancer Center Research Institute, Deputy Director

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Academic Background 【 Display / hide 】

Academic Background 【 Display / hide 】

• 1983.04

  -

  1989.03

  Keio University, Medical School

  University, Graduated

• 1989.04

  -

  1993.03

  Keio University, Postgraduate School, Keio University School of Medicine, Pathology Course

  Graduate School, Completed

Academic Degrees 【 Display / hide 】

Academic Degrees 【 Display / hide 】

• 博士 (医学), Keio University, Coursework, 1993.03

Licenses and Qualifications 【 Display / hide 】

Licenses and Qualifications 【 Display / hide 】

• 医師免許, 1989.05

• 死体解剖資格, 1992.02

• 日本病理学会病理専門医, 1994.08

• 日本臨床細胞学会細胞診専門医, 1998.12

• 日本病理学会病理専門医研修指導医, 2006.04

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Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Life Science / Human pathology (Cancer epigenomics)

Research Keywords 【 Display / hide 】

Research Keywords 【 Display / hide 】

• Molecular pathology

• Tumor pathology

• DNA methylation

• Multilayer/integrative comics analysis

• Genitourinary Pathology

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Books 【 Display / hide 】

Books 【 Display / hide 】

• 解明病理学 : 病気のメカニズムを解く

  加藤 光保, 金井 弥栄, 菅野 祐幸, 青笹 克之, 医歯薬出版, 2021

• DNA and Histone Methylation as Cancer Targets

  Arai E, Yotani T, Kanai Y., Elsevier, 2017

  Scope: Liver Cancer

• DNA and Histone Methylation in Liver Cancer

  Arai E., Yotani T., Kanai Y., Cancer Drug Discovery and Development, 2017

  　View Summary

  Epigenetic alterations, such as alterations of histone modification and DNA methylation, occur in a genome-wide manner under precancerous conditions resulting from hepatitis B virus (HBV) or hepatitis C virus (HCV) infection followed by chronic hepatitis and cirrhosis, or aberrant lipogenesis and abnormal metabolism of reactive oxygen species that characterize the pathophysiology of non-alcoholic steatohepatitis (NASH). Once DNA methylation alterations occur at the precancerous stage, they are stably preserved on DNA double strands through methylation maintenance by DNA methyltransferase 1 (DNMT1). DNA methylation alterations associated with abnormalities of DNA methyltransferase, such as overexpression of DNMT1 and splicing alterations of DNMT3B, participate in multistage hepatocarcinogenesis from the precancerous stage to the malignant progression stage and are correlated with aggressiveness of hepatocellular carcinomas (HCCs) and poorer outcome of affected patients. A number of tumor-related genes, such as ATK3, APC, BMP4, CCL20, CDH1, CDKN2A, CDKN2B, CSPG2, DAB2IP, DCC, DLC1, DPT, DPYSL3, EMILIN2, FZD7, GRASP, GSTP1, HIST1H4F, IGFALS, MGMT, MZB1, NAT2, NEFH, NFATC1, PAX4, PDSS2, PER3, PROZ, PYCARD, RASSF1A, SPDY1, RUNX3, SCGB1D1, SFN, SMPD3, SOCS1, TIMP3, TLX3, TM6SF1, TRIM33, TRIM58, WFDC6, WNK2 and ZFP41, are known to be silenced by DNA hypermethylation in human HCCs. It is believed that DNA methylation alterations could be excellent biomarkers for carcinogenetic risk estimation and prognostication. To facilitate clinical application of DNA methylation diagnosis, a scaled-down device that allows quick and accurate analysis, even in small hospitals and clinics, is now being developed. One therapeutic strategy against HCC proliferation could involve a combination of epigenetic modifiers, such as a DNA methylation inhibitor, a histone deacetylase inhibitor and an S-adenosylhomocysteine hydrolase inhibitor, to sensitize cancer cells to conventional chemotherapies, in addition to eradication of hepatitis viruses for personalized and/or pre-emptive medical care.

• DNA Methylation Alterations in Human Cancers

  Yae Kanai, Eri Arai, Elsevier Inc., 2012.12

  • Access to Document (DOI)

• DNA methylation alterations in human cancers. In: Epigenetics in Human Disease. ed. Tollefsbol T.

  Kanai Y, Arai E., Elsevier, Amsterdam, 2012,  Page： 29-52

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Papers 【 Display / hide 】

Papers 【 Display / hide 】

• Epigenetic profile of Japanese supercentenarians: a cross-sectional study.

  Komaki S, Nagata M, Arai E, Otomo R, Ono K, Abe Y, Ohmomo H, Umekage S, Shinozaki NO, Hachiya T, Sutoh Y, Otsuka-Yamasaki Y, Arai Y, Hirose N, Yoneyama A, Okano H, Sasaki M, Kanai Y, Shimizu A

  The lancet. Healthy longevity 4 （ 2 ） e83 - e90 2023.02

  • Access to Document (DOI)

• Single-cell analysis reveals a CD4+ T cell cluster that correlates with PD-1 blockade efficacy.

  H Kagamu, S Yamasaki, S Kitano, O Yamaguchi, A Mouri, A Shiono, ...

  Cancer Research, CAN-22 （Cancer research)  82 （ 24 ） 4641 - 4653 2022.10

  ISSN  0008-5472

  　View Summary

  CD4+ T-cell immunity helps clonal proliferation, migration, and cancer cell killing activity of CD8+ T cells and is essential in antitumor immune responses. To identify CD4+ T-cell clusters responsible for antitumor immunity, we simultaneously analyzed the naïve-effector state, Th polarization, and T-cell receptor clonotype based on single-cell RNA-sequencing data. Unsupervised clustering analysis uncovered the presence of a new CD4+ T-cell metacluster in the CD62Llow CD4+ T-cell subpopulation, which contained multicellular clonotypes associated with efficacy of programmed death-ligand 1 (PD-1) blockade therapy. The CD4+ T-cell metacluster consisted of CXCR3+CCR4-CCR6+ and CXCR3-CCR4-CCR6+ cells and was characterized by high expression of IL7 receptor and TCF7. The frequency of these cells in the peripheral blood significantly correlated with progression-free survival and overall survival of patients with lung cancer after PD-1 blockade therapy. In addition, the CD4+ metacluster in the peripheral blood correlated with CD4+ T-cell infiltration in the tumor microenvironment, whereas peripheral Th1 correlated with local CD8+ T-cell infiltration. Together, these findings suggest that CD62Llow CCR4-CCR6+ CD4+ T cells form a novel metacluster with predictive potential of the immune status and sensitivity to PD-1 blockade, which may pave the way for personalized antitumor immunotherapy strategies for patients. SIGNIFICANCE: The identification of a new CD4+ T-cell metacluster that corresponds with immune status could guide effective tumor treatment by predicting response to immunotherapy using peripheral blood samples from patients.

  • Access to Document (DOI)

• The Anterior Eye Chamber as a Visible Medium for In Vivo Tumorigenicity Tests

  E Inagaki, E Arai, S Hatou, T Sayano, H Taniguchi, K Negishi, Y Kanai, ...

  Stem Cells Translational Medicine （Stem cells translational medicine)  11 （ 8 ） 841 - 849 2022.06

  Accepted,  ISSN  2157-6564

  　View Summary

  Pluripotent stem cell (PSC)-based cell therapies have increased steadily over the past few years, and assessing the risk of tumor formation is a high priority for clinical studies. Current in vivo tumorigenesis studies require several months and depend strongly on the site of grafting. In this study, we report that the anterior eye chamber is preferable to the subcutaneous space for in vivo tumorigenesis studies for several reasons. First, cells can easily be transplanted into the anterior chamber and monitored in real-time without sacrificing the animals due to the transparency of the cornea. Second, tumor formation is faster than with the conventional subcutaneous method. The median tumor formation time in the subcutaneous area was 18.50 weeks (95% CI 10.20-26.29), vs. 4.0 weeks (95% CI 3.34-.67) in the anterior chamber (P = .0089). When hiPSCs were spiked with fibroblasts, the log10TPD50 was 3.26, compared with 4.99 when hiPSCs were transplanted without fibroblasts. There was more than a 40-fold difference in the log10TPD50 values with fibroblasts. Furthermore, the log10TPD50 for HeLa cells was 1.45 and 100% of animals formed tumors at a concentration greater than 0.1%, indicating that the anterior chamber tumorigenesis assays can be applied for cancer cell lines as well. Thus, our method has the potential to become a powerful tool in all areas of tumorigenesis studies and cancer research.

  • Access to Document (DOI)

• Lymphomatoid gastropathy/NK-cell enteropathy involving the stomach and intestine

  M Nakajima, M Shimoda, K Takeuchi, A Dobashi, T Kanai, Y Kanai, ...

  Journal of Clinical and Experimental Hematopathology, 21032 （The Japanese Society for Lymphoreticular Tissue Research)  advpub （ 0 ） 114 - 118 2022.04

  Accepted,  ISSN  1346-4280

  　View Summary

  <p>Lymphomatoid gastropathy (LyGa)/natural killer (NK)-cell enteropathy (NKCE) is recognized as a benign NK-cell lymphoproliferative disease. Due to its histological similarity to NK/T cell lymphoma, it is easy to misdiagnose, leading to unnecessary chemotherapy and poor quality of life. This disease is typically observed in the small and large intestines in North America, whereas almost all cases in Japan occur locally in the stomach. Only 11 LyGa/NKCE cases involving both gastric and intestinal lesions have been reported, and there are few reports providing endoscopic images throughout the gastrointestinal tract. We report a case of LyGa/NKCE involving both the stomach and small and large intestines with detailed upper gastrointestinal endoscopy, colonoscopy, capsule endoscopy and pathology images. Its pathogenesis currently remains elusive, but most patients with LyGa/NKCE in Japan have Helicobacter pylori (H. pylori) infection. Our patient was also positive for H. pylori infection at disease onset, but after receiving eradication therapy, ulcerative lesions in both stomach and intestine regressed and no recurrence was observed. This case suggests a link between the pathogenesis of LyGa/NKCE and H. pylori infection.</p>

  • Access to Document (DOI)
  • CiNii Research

• Alteration of protein glycosylation in renal carcinogenesis

  Kitazume Yoshiko, Arai Eri, Matsuda Atsushi, Kakuda Shuichi, Ohara Kentaro, Maeshima Akiko, Kuno Atsushi, Yoshida Teruhiko, Kanai Yae

  CANCER SCIENCE 113   1284 - 1284 2022.02

  ISSN  1347-9032

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

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

• Elucidation of aging mechanisms by regulation of NAD+ and epigenome and development of new anti-aging interventions

  Kanai, Yae

  科学研究費補助金研究成果報告書 2020

• Development of biliary and pancreatic tumor cell bank using organoid culture and its application to personalized therapy

  Kanai, Yae

  科学研究費補助金研究成果報告書 2019

• Risk estimation of pancreatic adenocarcinomas based on epigenome-wide association study

  Kanai, Yae

  科学研究費補助金研究成果報告書 2018

• Cross-organ analysis of DNA methylation alteration during multi-organ carcinogenesis

  Kanai, Yae

  科学研究費補助金研究成果報告書 2018

• Analysis of cancer-associated fibroblasts from the perspective of proteinases and epigenetics

  Kanai, Yae

  科学研究費補助金研究成果報告書 2018

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Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• 非アルコール性脂肪性肝炎由来肝細胞がんにおけるSPHK1ならびにLTB遺伝子のDNAメチル化異常(DNA methylation alterations of SPHK1 and LTB in non-alcoholic steatohepatitis-related hepatocellular carcinomas)

  津田 昇, 田 迎, 藤本 真央, 藏本 純子, 牧内 里美, 尾島 英知, 後藤 政広, 平岡 伸介, 吉田 輝彦, 金井 弥栄, 新井 恵吏

  日本癌学会総会記事 ((一社)日本癌学会)  81回   E - 1005 2022.09

  ISSN  0546-0476

• 諸臓器の多段階発がん過程早期に普遍的なDNAメチル化プロファイル(Genome-wide DNA methylation profiling during the early step of multistage carcinogenesis in various organs)

  中山 雄二, 新井 恵吏, 藤本 真央, 津田 昇, 牧内 里美, 田 迎, 藏本 純子, 金井 弥栄

  日本癌学会総会記事 ((一社)日本癌学会)  81回   P - 1099 2022.09

  ISSN  0546-0476

• 誘導性CRISPR/dCas9を用いりC19MCの肝内胆管癌オルガノイドの分化における役割の解明(Exploring the Role of C19MC on the differentiation Status of IHCC Organoids by Inducible CRISPR/dCas9)

  葉 子祥, 松崎 潤太郎, 及川 千尋, 金井 弥栄, 齋藤 義正

  日本癌学会総会記事 ((一社)日本癌学会)  81回   J - 1017 2022.09

  ISSN  0546-0476

• 肺腺がんのDNAメチル化プロファイルに対する免疫微小環境の影響(Impact of the immune microenvironment on genome-wide DNA methylation profiles of lung adenocarcinomas)

  河原 徹, 藤本 真央, 下田 将之, 淺村 尚生, 金井 弥栄, 新井 恵吏

  日本癌学会総会記事 ((一社)日本癌学会)  81回   P - 1093 2022.09

  ISSN  0546-0476

• 全血由来DNAにおけるエピゲノム関連解析による淡明細胞型腎細胞がんの検出に有用なDNAメチル化バイオマーカー候補の同定(Potential DNA methylation biomarkers for ccRCC identified by a whole blood-based epigenome-wide association study)

  大桃 秀樹, 新井 恵吏, 吉田 輝彦, 金井 弥栄, 清水 厚志

  日本癌学会総会記事 ((一社)日本癌学会)  81回   P - 1088 2022.09

  ISSN  0546-0476

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Presentations 【 Display / hide 】

Presentations 【 Display / hide 】

• Quantification of DNA methylation for carcinogenic risk estimation in patients with non-alcoholic steatohepatitis.

  Junko Kuramoto, Eri Arai, Mao Fujimoto, Ying Tian, Yuriko Yamada, Takuya Yotani, Satomi Makiuchi, Noboru Tsuda, Hidenori Ojima, Moto Fukai, Yosuke Seki, Kazunori Kasama, Nobuaki Funahashi, Haruhide Udagawa, Takao Nammo, Kazuki Yasuda, Akinobu Taketomi, Tatsuya Kanto, Yae Kanai.

  America Association for Cancer Research Annual Meeting 2022, 

  2022.04

• Correlations between genome-wide DNA methylation profiles and genomic driver aberrations during multistage lung adenocarcinogenesis.

  Kenichi Hamada, Ying Tian, Mao Fujimoto, Yoriko Takahashi, Takashi Kohno, Koji Tsuta, Shun-ichi Watanabe, Teruhiko Yoshida, Hisao Asamura, Yae Kanai, Eri Arai.

  America Association for Cancer Research Annual Meeting 2021, 

  2021.04

• Simple vs. comprehensive prediction models of homologous recombination deficiency based on mutational and clinical features in three independent breast cancer datasets.

  Maki Tanioka, Tomoko Watanabe, Takayuki Honda, Hirohiko Totsuka, Eri Arai, Yae Kanai, Kouya Shiraishi, Kenji Tamura, Takashi Kohno.

  America Association for Cancer Research Annual Meeting 2020, 

  2020.04

• Establishment of diagnostic criteria for upper urinary tract urothelial carcinoma based on genome-wide DNA methylation analysis.

  Mao Fujimoto, Eri Arai, Koji Tsumura, Takuya Yotani, Yuriko Yamada, Yoriko Takahashi, Akiko Miyagi Maeshima, Hiroyuki Fujimoto, Teruhiko Yoshida, Yae Kanai.

  America Association for Cancer Research Annual Meeting 2020 , 

  2020.04

• Intratumor DNA methylation heterogeneity reflects differentiation plasticity and malignant progression of human glioblastoma: a methylome analysis using microdissected specimens.

  Kentaro Ohara, Eri Arai, Hikaru Sasaki, Masashi Nakatsukasa, Kazunari Yoshida, Yae Kanai.

  11th AACR-JCA Joint Conference on Breakthroughs in Cancer. (Hawaii) , 

  2019.02

  , 

  Poster presentation

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

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

• Pathological diagnosis based on integration of morphological images and multi-layer omics data by artificial intelligence

  2021.04

  -

  2024.03

  Keio University, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), No Setting

  　View Summary

  本研究は、人工知能 (AI)の支援を受けて病理形態像とゲノム等オミックス情報を融合させ、がんの治療奏効性・有害事象・予後を予測する深層学習モデルを構築することを目的とする。予測時のAIの着眼点を可視化し、形態学的診断基準に翻訳して、病理医が顕微鏡で見るだけでモデルと同等の治療奏効性・有害事象・予後予測を可能にすることを目指す。悪性度が高い腎淡明細胞がんのCpGアイランドメチル化形質 (CIMP)の予測モデルを構築する過程で、病理画像とオミックスデータを統合する至適研究手法を確立し、「病理医とAIの創造的協働による、オミックス情報を統合した新しい病理診断の創出 (病理診断学の革新)」を図る。

• Elucidation of Aging Mechanisms by Regulation of NAD+ and Epigenome and Development of New Anti-Aging Interventions

  2019.06

  -

  2021.03

  Keio University, Grants-in-Aid for Scientific Research, Saito Yoshimasa, Challenging Research (Exploratory), No Setting

  　View Summary

  To elucidate the molecular mechanism of aging, we established organoids from the intestinal epithelium of aging mice and analyzed gene expression changes and epigenomic changes.
  The organoids from aged mice showed reduced proliferative capacity and tissue building ability. In addition, epigenomic changes led to decreased gene expression of stem cell markers such as Lgr5 and Wnt signaling pathway in organoids from aged mice. In addition, administration of nicotinamide mononucleotide (NMN), an NAD+ precursor, changed the morphology of intestinal epithelial organoids from aged mice to that of young mice and restored the expression of stem cell-related genes, suggesting that NMN increases NAD+ activity and has an anti-aging effect.

• Established epigenetic treatment for chemotherapy-resistant metastatic bladder cancer

  2019.04

  -

  2022.03

  University of Toyama, Grants-in-Aid for Scientific Research, Nishiyama Naotaka, Grant-in-Aid for Scientific Research (C), No Setting

  　View Summary

  Chromatin accessibility was analyzed by the AcceSssIble assay, revealing that the CDDP / GEM-resistant cell lines differ in histone-modified regions compared to the parental strain. It was clarified that the change in chromatin structure due to histone modification contributed to the drug resistance. Comprehensive DNA methylation analysis revealed that resistance was not contributed by genetic changes at a particular site, but by both genome-wide DNA methylation changes and structural changes due to histone modifications. In an in vivo study, low-dose 5-aza-CdR showed a synergistic effect with CDDP administration, and a growth-suppressing effect was also observed in resistant strains.

• 免疫応答モニタリングによるがん免疫の全容理解に基づく新規層別化マーカーの開発

  2019

  -

  2022

  日本医療研究開発機構, 次世代治療・診断実現のための創薬基盤技術開発事業, Coinvestigator(s)

• NASH 肝がんの リピド・ゲノミクス 研究に基づく個別化医療の開発

  2018

  -

  2022

  日本医療研究開発機構, 肝炎等克服実用化研究事業, Coinvestigator(s)

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Intellectual Property Rights, etc. 【 Display / hide 】

Intellectual Property Rights, etc. 【 Display / hide 】

• 尿路上皮癌のリスク判定方法

  Date applied： PCT/JP2019/011442  2019.03 

  Patent, Joint

• 子宮体癌の予後の判定方法

  Date applied： 特願2018-228276  2018.11 

  Patent, Joint

• Method for assessing risk of hepatocellular carcinoma

  Date applied： PCT/JP2018/031092  2018.08 

  Patent, Joint

• 尿路上皮癌のリスク判定方法

  Date applied： 特願2018-051464  2018.03 

  Patent, Single

• 肝細胞癌のリスク評価方法

  Date applied： 特願2017-160284  2017.08 

  Patent, Joint

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Awards 【 Display / hide 】

Awards 【 Display / hide 】

• JCA Women Scientists Award

  Yae Kanai, 2018.09, Japanese Cancer Association, Molecular pathological approach ti epigenome mechanisms of multistage human carcinogenesis

  Type of Award： Award from Japanese society, conference, symposium, etc.

• Tamiya Prize

  2006.02, Foundation for Promotion of Cancer Research, Cancer development, invasion and metastasis: Epigenetic research based on histopathological approach

  Type of Award： Award from publisher, newspaper, foundation, etc.

• Incitement Award of the Japanese Cancer Association

  2003.09, Japanese Cancer Association, DNA methylation abnormalities participating in multistage human carcinogenesis

  Type of Award： Award from Japanese society, conference, symposium, etc.

• Incitement Award of the Japanese Society of Pathology

  Yae Kanai, 2002.03, Japanese Society of Pathology, DNA methylation alterations during multistage human carcinogenesis

  Type of Award： Award from Japanese society, conference, symposium, etc.

• Baelz Prize

  Setsuo Hirohashi, Atsushi Ochiai, Yae Kanai, 2000.11, ベルツ財団, Inactivation of E-cadherin cell adhesion system in human cancer invasion and metastasis

Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• GENERAL PATHOLOGY

  2023

• DISEASES OF ORGAN SYSTEMS

  2023

• CUTTING-EDGE GENOMIC MEDICINE

  2023

• BASIC ONCOLOGY

  2023

• ADVANCED PATHOLOGY

  2023

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Courses Previously Taught 【 Display / hide 】

Courses Previously Taught 【 Display / hide 】

• General Pathology

  Keio University

  2018.04

  -

  2019.03

  , 

  Full academic year, Lecture

• Diseases of organ systems

  Keio University

  2018.04

  -

  2019.03

  , 

  Full academic year, Lecture

• 症例検討 (基礎臨床統合医学)

  Keio University

  2018.04

  -

  2019.03

• 医学概論 (大学院医学研究科修士課程)

  Keio University

  2018.04

  -

  2019.03

• 医学特別講義 (大学院医学研究科博士課程)

  Keio University

  2018.04

  -

  2019.03

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Memberships in Academic Societies 【 Display / hide 】

Memberships in Academic Societies 【 Display / hide 】

• Associate member, Science Council of Japan, 

  2006

  -

  Present

• 日本病理学会: 拡大常任理事・学術評議員 (病理専門医、病理専門医研修指導医、分子病理専門医、ゲノム病理診断検討委員会委員長・ゲノム研究用病理組織検体取扱い規程策定委員会委員長・ゲノム病理標準化講習会委員会委員長・教育委員会委員長・病理診療ガイドライン作成委員会委員長・固形癌HER2病理診断ガイドライン策定ワーキンググループ委員長・企画委員会委員・学術委員会委員・編集委員会委員・ゲノム診療用病理組織検体取扱い規程策定ワーキンググループ委員・病理専門医制度運営委員会委員等), 

  1989

  -

  Present

• 日本癌学会: 評議員 (女性科学者委員会委員), 

  1994.08

  -

  Present

• 日本臨床細胞学会

  　

• 日本エピジェネティクス研究会 (幹事)

  　

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Committee Experiences 【 Display / hide 】

Committee Experiences 【 Display / hide 】

• 2021

  -

  Present

  厚生労働省がんゲノム医療中核拠点病院等の指定要件に関するワーキンググループ構成員

• 2020.04

  -

  Present

  日本学術振興会学術システム研究センタープログラムオフィサー (専門研究員)

• 2020

  -

  Present

  科学技術振興機構ＮＢＤＣヒトデータベース倫理審査委員会委員

• 2017

  -

  Present

  日本医療研究開発機構プログラムオフィサー・課題評価委員会委員・アドバイザー

• 2015

  -

  2016

  文部科学省科学研究費補助金における評価に関する委員会生物系委員会委員

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