KANAI Yae

写真a

Affiliation

School of Medicine, Department of Pathology Kanai Laboratory （Shinanomachi）

Position

Professor （Keio University）

Related Websites

External Links
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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 】

  • 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

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Academic Degrees 【 Display / hide 】

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

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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 】

  • Life Science / Human pathology (Cancer epigenomics)

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Research Keywords 【 Display / hide 】

  • Molecular pathology

  • Tumor pathology

  • DNA methylation

  • Multilayer/integrative comics analysis

  • Genitourinary Pathology

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Books 【 Display / hide 】

  • CPC形式でわかる身につく病理所見の見かた、病態の考えかた

    藏本 純子, 金井 弥栄, 鈴木 秀和, 羊土社, 2023

  • 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

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Papers 【 Display / hide 】

  • Clinicopathological significance of androgen receptor expression in extramammary Paget disease: An analysis of 92 patients

    Kuramoto J., Kobayashi K., Hirai I., Nakamura Y., Funakoshi T., Kanai Y.

    Pathology Research and Practice （Pathology Research and Practice)  249   154775 2023.09

    ISSN  03440338

    　View Summary

    Extramammary Paget disease (EMPD) is a rare cutaneous malignant neoplasm arising in apocrine gland-rich areas. Although – like normal apocrine glands – EMPD frequently expresses androgen receptor (AR), the clinical significance of AR expression remains unclear. The present study investigated the clinicopathological impact of AR expression in EMPD. Immunohistochemistry for AR was performed in a retrospective cohort of 92 EMPD patients with 108 EMPD lesions, including 102 primary lesions, five lymph node [LN] metastases and one local recurrence. The total AR staining score was calculated as staining intensity score (IS 0–3) × positive-cell percentage score (PS 1–4). Expression levels were graded as Grade 1 (scores 0 and 1), Grade 2 (scores 2–4), and Grade 3 (scores 6–12). Higher expression grade was correlated with tumor thickness (P = 0.011), LN metastasis (P = 0.008), and higher EMPD stage (P = 0.023). Grade 1 EMPDs did not invade into the dermis and did not generate metastatic and/or recurrent lesions, whereas only Grade 2 or 3 EMPDs did so. AR expression in invasive components was significantly higher (P = 0.023) than in non-invasive components remaining within the epidermis. AR expression was further elevated in metastatic and/or recurrent lesions relative to locally invasive lesions (P = 0.014). These results clearly indicate that increased AR expression is associated with malignant progression of EMPD and that androgen blockade might be an effective therapy. Furthermore, AR expression assessed by immunohistochemistry may have potential for prediction of LN metastasis and local recurrence in EMPD.

  • Tumor-infiltrating Leukocyte Profiling Defines Three Immune Subtypes of NSCLC with Distinct Signaling Pathways and Genetic Alterations.

    Aoki K, Nishito Y, Motoi N, Arai Y, Hiraoka N, Shibata T, Sonobe Y, Kayukawa Y, Hashimoto E, Takahashi M, Fujii E, Nishizawa T, Fukuda H, Ohashi K, Arai K, Mizoguchi Y, Yoshida Y, Watanabe SI, Yamashita M, Kitano S, Sakamoto H, Nagata Y, Mitsumori R, Ozaki K, Niida S, Kanai Y, Hirayama A, Soga T, Maruyama T, Tsukada K, Yabuki N, Shimada M, Kitazawa T, Natori O, Sawada N, Kato A, Yoshida T, Yasuda K, Mizuno H, Tsunoda H, Ochiai A

    Cancer research communications 3 （ 6 ） 1026 - 1040 2023.06

  • 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

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

    日本病理学会会誌 （(一社)日本病理学会)  112 （ 1 ） 329 - 329 2023.03

    ISSN  0300-9181

  • New horizons for cancer research driven by histopathological approaches

    Enomoto, A; Kanai, Y

    CANCER SCIENCE 114   919 - 919 2023.02

    ISSN  1347-9032

  • 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 （The Lancet Healthy Longevity)  4 （ 2 ） e83 - e90 2023.02

    ISSN  2666-7568

    　View Summary

    BACKGROUND: Centenarians and supercentenarians with exceptional longevity are excellent models for research towards improvements of healthy life expectancy. Extensive research regarding the maintenance and reduction of epigenetic age has provided insights into increasing healthy longevity. To this end, we explored the epigenetic signatures reflecting hallmarks of exceptional healthy longevity, including avoidance of age-related diseases and cognitive functional decline. METHODS: In this cross-sectional study, we enrolled Japanese non-centenarians (eligible participants aged 20-80 years) from the Tohoku Medical Megabank Community-Based Cohort Study and centenarians and supercentenarians (aged 101-115 years) from the Tokyo Centenarian Study and the Japanese Semi-supercentenarian Study. We assessed participants' whole-blood DNA methylation profiles and then developed sex-specific and non-specific first-generation epigenetic clocks by elastic net regression, calculated individuals' epigenetic ages, and assessed their age acceleration. We also screened for age-related CpG sites in non-centenarians by epigenome-wide linear regression analyses and ANOVA. We subsequently investigated which CpG sites in centenarians and supercentenarians had DNA methylation patterns following the age-related findings obtained from non-centenarians and which did not. We further characterised CpG sites with hypermethylation or hypomethylation in the centenarians and supercentenarians using enrichment and protein-protein interaction network analyses. FINDINGS: We enrolled 421 non-centenarians (231 [55%] women and 190 [45%] men; age range 20-78 years), recruited between May 20, 2013, and March 31, 2016, and 94 centenarians and supercentenarians (66 women [70%] and 28 [30%] men; age range 101-115 years), recruited between Jan 20, 2001, and April 17, 2018. Non-sex-specific epigenetic clock showed the highest accuracy (r=0·96) based on which centenarians and supercentenarians had negative epigenetic age acceleration. Epigenome-wide association analyses further showed that centenarians and supercentenarians had younger-than-expected epigenetic states (DNA methylation profiles similar to those of non-centenarians) for 557 CpG sites enriched in cancer-related and neuropsychiatric-related genes, whereas these individuals had advanced (or older) epigenetic states for 163 CpG sites represented by genes related to TGF-β signalling, which is involved in anti-inflammatory responses and known to contribute to healthy ageing. INTERPRETATION: These results indicate that exceptionally healthy longevity depends not only on maintaining young epigenetic states but also on advanced states of specific epigenetic regions. FUNDING: The Japan Agency for Medical Research and Development, KDDI Research, and Keio University. TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.

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

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Reviews, Commentaries, etc. 【 Display / hide 】

  • 難治性精巣腫瘍に対して化学療法とdesperation surgeryを施行し完全奏効を得た一例

    蛭田 慎之介, 田中 伸之, 小森 貴大, 岩澤 智裕, 小坂 威雄, 水野 隆一, 浅沼 宏, 大家 基嗣, 新井 恵吏, 金井 弥栄

    泌尿器外科 (医学図書出版(株))  36 ( 10 ) 1167 - 1167 2023.10

    ISSN  0914-6180

  • 尿道憩室に存在した腸上皮に発生した腺癌の1例

    星野 佑介, 松本 一宏, 馬場 優人, 秋田 大宇, 新井 恵吏, 安水 洋太, 田中 伸之, 武田 利和, 森田 伸也, 小坂 威雄, 水野 隆一, 浅沼 宏, 陣崎 雅弘, 金井 弥栄, 大家 基嗣

    泌尿器外科 (医学図書出版(株))  36 ( 10 ) 1162 - 1163 2023.10

    ISSN  0914-6180

  • オンライン国際交流プログラムにより医療系学生の異文化理解能力が向上した(An online international exchange program improves intercultural skills in health profession students)

    井原 慶子, Kim Hakyoung, Kumar Shari, Noel Geoffroy, McWatt Sean, Green Alexander, 櫻井 武, 門川 俊明, 金井 弥栄, Wu Anette

    医学教育 ((一社)日本医学教育学会)  54 ( Suppl. ) 264 - 264 2023.07

    ISSN  0386-9644

  • 長寿者のエピゲノム解析

    小巻 翔平, 永田 雅俊, 新井 恵吏, 大友 亮, 小野 加奈子, 阿部 由紀子, 大桃 秀樹, 梅影 創, 篠崎 夏子, 八谷 剛史, 須藤 洋一, 山崎 弥生[大塚], 新井 康通, 広瀬 信義, 米山 暁夫, 岡野 栄之, 佐々木 真理, 金井 弥栄, 清水 厚志

    日本抗加齢医学会総会プログラム・抄録集 ((一社)日本抗加齢医学会)  23回   220 - 220 2023.06

  • HER2検査の新たなパラダイム　固形癌HER2病理診断ガイダンス　第3版改訂に向けて

    畑中 豊, 長尾 俊孝, 藤井 誠志, 津田 均, 九嶋 亮治, 羽場 礼次, 佐々木 毅, 金井 弥栄

    日本病理学会会誌 ((一社)日本病理学会)  112 ( 1 ) 204 - 204 2023.03

    ISSN  0300-9181

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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 】

  • 尿路上皮がんに対する新規エピゲノム解析による治療効果予測バイオマーカー開発

    2023.04
    -
    2028.03

    Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), No Setting

    　View Summary

    本研究の目的は、約500例を目標とする切除不能尿路上皮がんの多施設共同前向き観察研究から得られた組織・血液を用いてエピゲノム解析を行い、1・2次治療に向けた治療効果診断マーカーを開発し、予後不良である切除不能尿路上皮がんの、治療のブレイクスルー創出と治療成績の向上に貢献する。（１）尿路上皮がん手術材料より組織検体を採取し、エピゲノム解析により治療効果予測バイオマーカーを開発すると同時に、その信頼度の前向き検証を行う。新たに開発した診断基準で予後予測し、最適な治療法を目指した医師主導治験等に進むための、基盤となる知見を得る。

  • 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)

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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 】

  • 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

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Courses Taught 【 Display / hide 】

  • PATHOLOGY: SEMINAR

    2024

  • PATHOLOGY: PRACTICE

    2024

  • PATHOLOGY

    2024

  • GENERAL PATHOLOGY

    2024

  • DISEASES OF ORGAN SYSTEMS

    2024

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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 】

  • 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 】

  • 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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