Kazumasa Aoyama

写真a

Affiliation

Faculty of Pharmacy, Department of Pharmacy Department of Hygienic Chemistry (Shiba-Kyoritsu)

Position

Research Associate/Assistant Professor/Instructor
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Career 【 Display / hide 】

  • 2014.04
    -
    2017.06

    千葉大学医学研究院 細胞分子医学研究室（岩間厚志 教授), 特任研究員

  • 2017.07
    -
    2018.09

    千葉大学医学研究院 細胞分子医学研究室 (岩間厚志 教授), 特任助教

  • 2018.09
    -
    2021.09

    Pulmonary Branch, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH) (Dr. Joel Moss), Research Fellow

  • 2021.10
    -
    2023.08

    東京大学医科学研究所 幹細胞分子医学分野 (岩間厚志 教授), 特任助教

  • 2023.09
    -
    Present

    慶應義塾大学薬学部 衛生化学講座（多胡めぐみ 教授）, 助教

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Academic Background 【 Display / hide 】

  • 2003.04
    -
    2008.03

    Chiba University, 薬学部, 総合薬品科学科

    University, Graduated

  • 2008.04
    -
    2010.03

    Chiba University, 大学院医学薬学府（薬学研究院）総合薬品科学専攻, 修士課程

    Graduate School, Completed, Master's course

  • 2010.04
    -
    2014.03

    Chiba University, 大学院医学薬学府（薬学研究院）先端生命科学専攻, ４年博士課程

    Graduate School, Completed, Doctoral course

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Academic Degrees 【 Display / hide 】

  • 博士（医薬学）, Chiba University, Coursework, 2014.03

    核内 c-Abl チロシンキナーゼの機能解析：核内 F-actin bundle 形成と ヒストン脱アセチル化酵素を介したクロマチン構造変換

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Licenses and Qualifications 【 Display / hide 】

  • コーチングスキルアドバイザー(一般社団法人トラストコーチング）, 2020.11

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Research Keywords 【 Display / hide 】

  • 転写制御機構（エピジェネティック制御、ヒストン修飾、ポリコーム抑制複合体、EZH1/2）

  • 老化研究（セノリティックス、アンチエンジング）

  • 食品科学（コーヒー）

  • 創薬研究

  • がん（骨髄異形成症候群、骨髄増殖性腫瘍）

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Papers 【 Display / hide 】

  • Identification of MRVI1-Interacting Proteins by Biotin-Based Proximity Labeling Reveals NPM-ALK-Dependent Interaction Dynamics.

    Higashi K, Tanaka Y, Kosako H, Aoyama K,

    J Biochem. in press  2025.10

    Joint Work, Lead author, Last author, Corresponding author, Accepted

  • Targeting a therapy-resistant subpopulation with vulnerability to splicing pathway inhibition in multiple myeloma.

    1. Kamiya T, Ajiro M, Oshima M, Koide S, Nakajima-Takagi Y, Aoyama K, Tsuchiya A, Kaito S, Itokawa N, Ito R, Yamaguchi K, Furukawa Y, Rahmutulla B, Kaneda A, Shimizu T, Doki N, Kikuchi T, Tsukada N, Yamashita M, Okamoto S, Yoshimi A, Kataoka K, and Iwama A.

    Blood Cancer Discov. in press  2025.09

    Research paper (scientific journal), Joint Work, Accepted

  • Inhibition of TOPORS ubiquitin ligase augments the efficacy of DNA hypomethylating agents through DNMT1 stabilization

    Kaito S, Aoyama K, Oshima M, Tsuchiya A, Miyota M, Yamashita M, Koide S, Nakajima-Takagi Y, Kozuka-Hata H, Oyama M, Yabushita T, Ueno M, Hirao A, Tohyama K, Yamaguchi K, Furukawa Y, Kosako H, Yoshimi A, Goyama S, Nannya Y, Ogawa S, Agger K, Helin K, Koseki H, Nishiyama A, Nakanishi M, and Iwama A,

    Nature Communications (Springer Science and Business Media LLC)  15 ( 1 )  2024.08

    Research paper (scientific journal), Joint Work, Accepted

    　View Summary

    Abstract

    DNA hypomethylating agents (HMAs) are used for the treatment of myeloid malignancies, although their therapeutic effects have been unsatisfactory. Here we show that CRISPR-Cas9 screening reveals that knockout of topoisomerase 1-binding arginine/serine-rich protein (TOPORS), which encodes a ubiquitin/SUMO E3 ligase, augments the efficacy of HMAs on myeloid leukemic cells with little effect on normal hematopoiesis, suggesting that TOPORS is involved in resistance to HMAs. HMAs are incorporated into the DNA and trap DNA methyltransferase-1 (DNMT1) to form DNA-DNMT1 crosslinks, which undergo SUMOylation, followed by proteasomal degradation. Persistent crosslinking is cytotoxic. The TOPORS RING finger domain, which mediates ubiquitination, is responsible for HMA resistance. In TOPORS knockout cells, DNMT1 is stabilized by HMA treatment due to inefficient ubiquitination, resulting in the accumulation of unresolved SUMOylated DNMT1. This indicates that TOPORS ubiquitinates SUMOylated DNMT1, thereby promoting the resolution of DNA-DNMT1 crosslinks. Consistently, the ubiquitination inhibitor, TAK-243, and the SUMOylation inhibitor, TAK-981, show synergistic effects with HMAs through DNMT1 stabilization. Our study provides a novel HMA-based therapeutic strategy that interferes with the resolution of DNA-DNMT1 crosslinks.

  • The pathogenetic significance of exhausted T cells in a mouse model of mature B cell neoplasms

    Shibamiya, A., Miyamoto-Nagai, Y., Koide, S., Oshima, M., Rizq, O., Aoyama, K., Nakajima-Takagi, Y., Kato, R., Kayamori, K., Isshiki, Y., Oshima-Hasegawa, N., Muto, T., Tsukamoto, S., Takeda, Y., Koyama-Nasu, R., Chiba, T., Honda, H., Yokote, K., Iwama, A., Sakaida, E. and Mimura, N.

    Cancer Immunol Immunother 72 ( 8 ) 2635 - 2648 2023.08

    Research paper (scientific journal), Accepted,  ISSN  0340-7004

    　View Summary

    Dysfunctional anti-tumor immunity has been implicated in the pathogenesis of mature B cell neoplasms, such as multiple myeloma and B cell lymphoma; however, the impact of exhausted T cells on disease development remains unclear. Therefore, the present study investigated the features and pathogenetic significance of exhausted T cells using a mouse model of de novo mature B cell neoplasms, which is likely to show immune escape similar to human patients. The results revealed a significant increase in PD-1(+) Tim-3(-) and PD-1(+) Tim-3(+) T cells in sick mice. Furthermore, PD-1(+) Tim-3(+) T cells exhibited direct cytotoxicity with a short lifespan, showing transcriptional similarities to terminally exhausted T cells. On the other hand, PD-1(+) Tim-3(-) T cells not only exhibited immunological responsiveness but also retained stem-like transcriptional features, suggesting that they play a role in the long-term maintenance of anti-tumor immunity. In PD-1(+) Tim-3(-) and PD-1(+) Tim-3(+) T cells, the transcription factors Tox and Nr4a2, which reportedly contribute to the progression of T cell exhaustion, were up-regulated in vivo. These transcription factors were down-regulated by IMiDs in our in vitro T cell exhaustion analyses. The prevention of excessive T cell exhaustion may maintain effective anti-tumor immunity to cure mature B cell neoplasms.

  • Polycomb repressive complex 1.1 coordinates homeostatic and emergency myelopoiesis

    Nakajima-Takagi, Y., Oshima, M., Takano, J., Koide, S., Itokawa, N., Uemura, S., Yamashita, M., Andoh, S., Aoyama, K., Isshiki, Y., Shinoda, D., Saraya, A., Arai, F., Yamaguchi, K., Furukawa, Y., Koseki, H., Ikawa, T. and Iwama, A.

    Elife 12 2023.06

    Research paper (scientific journal), Accepted,  ISSN  2050-084x

    　View Summary

    Polycomb repressive complex (PRC) 1 regulates stem cell fate by mediating mono-ubiquitination of histone H2A at lysine 119. While canonical PRC1 is critical for hematopoietic stem and progenitor cell (HSPC) maintenance, the role of non-canonical PRC1 in hematopoiesis remains elusive. PRC1.1, a non-canonical PRC1, consists of PCGF1, RING1B, KDM2B, and BCOR. We recently showed that PRC1.1 insufficiency induced by the loss of PCGF1 or BCOR causes myeloid-biased hematopoiesis and promotes transformation of hematopoietic cells in mice. Here we show that PRC1.1 serves as an epigenetic switch that coordinates homeostatic and emergency hematopoiesis. PRC1.1 maintains balanced output of steady-state hematopoiesis by restricting C/EBPα-dependent precocious myeloid differentiation of HSPCs and the HOXA9- and β-catenin-driven self-renewing network in myeloid progenitors. Upon regeneration, PRC1.1 is transiently inhibited to facilitate formation of granulocyte-macrophage progenitor (GMP) clusters, thereby promoting emergency myelopoiesis. Moreover, constitutive inactivation of PRC1.1 results in unchecked expansion of GMPs and eventual transformation. Collectively, our results define PRC1.1 as a novel critical regulator of emergency myelopoiesis, dysregulation of which leads to myeloid transformation.

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Reviews, Commentaries, etc. 【 Display / hide 】

  • Epigenetic Memories in Hematopoietic Stem and Progenitor Cells

    Aoyama, K., Itokawa, N., Oshima, M. and Iwama, A.

    Cells 11 ( 14 )  2022.07

    Lead author, Corresponding author,  ISSN  2073-4409

    　View Summary

    The recent development of next-generation sequencing (NGS) technologies has contributed to research into various biological processes. These novel NGS technologies have revealed the involvement of epigenetic memories in trained immunity, which are responses to transient stimulation and result in better responses to secondary challenges. Not only innate system cells, such as macrophages, monocytes, and natural killer cells, but also bone marrow hematopoietic stem cells (HSCs) have been found to gain memories upon transient stimulation, leading to the enhancement of responses to secondary challenges. Various stimuli, including microbial infection, can induce the epigenetic reprogramming of innate immune cells and HSCs, which can result in an augmented response to secondary stimulation. In this review, we introduce novel NGS technologies and their application to unraveling epigenetic memories that are key in trained immunity and summarize the recent findings in trained immunity. We also discuss our most recent finding regarding epigenetic memory in aged HSCs, which may be associated with the exposure of HSCs to aging-related stresses.

  • マルチフェイスな転写抑制因子 EZH2 のがん抑制修飾 (EZH2-K735me1)

    青山和正

    ファルマシア 57 (3), 230-230  2021

  • Role of EZH1 in EZH2-deficient hematopoiesis

    Aoyama K

    Nature Research Cancer Community (Invited by Editorial Office Leukemia), Online https://cancercommunity.nature.com/posts/role-of-ezh1-in-ezh2-deficient-hematopoiesis  2020.08

    Lead author, Last author, Corresponding author

  • 核内c-Ablチロシンキナーゼの新規機能：核内F-actin bundleの形成

    青山和正

    日本薬学会 生物系薬学部会 学生コロキウム 私の研究紹介, Online http://bukai.pharm.or.jp/bukai_seibutsu/pdf/research20_251204.pdf.  2013.12

    Lead author, Last author, Corresponding author

  • 慢性骨髄性白血病の新規治療戦略 ～imatinib耐性を克服するSIRT1阻害剤

    青山和正

    日本薬学会 生物系薬学部会 学生コロキウム ジャーナルクラブ, Online http://bukai.pharm.or.jp/bukai_seibutsu/pdf/journal17_240525.pdf.  2012.05

    Lead author, Last author, Corresponding author

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Presentations 【 Display / hide 】

  • Therapeutic Targeting of Epigenomic Dysregulation in Inflammation-Associated Myelodysplastic Syndrome (MDS)

    青山和正 (口頭)

    シンポジウム：ミクロとマクロの視点から読み解く炎症病態〜免疫変容、薬物治療抵抗性、病的ストレスを契機として〜 第99回日本薬理学会年会 (仙台) , 

    2026.03
    , 

    Symposium, workshop panel (public)

  • EZH2機能喪失型骨髄異形成症候群に対する創薬標的分子の探索.

    青山和正

    日本白血病研究基金・日本血液学会共催 公開シンポジウム 高久史磨賞受賞者講演 , 

    2025.10
    , 

    Oral presentation (invited, special)

  • NPM-ALK発現細胞におけるTGM1の相互作用分子の同定及び機能解析

    田口想（口頭）、東孝輔、田中祐貴、小迫英尊、青山和正

    第69回日本薬学会関東支部大会(埼玉）, 

    2025.09
    , 

    Oral presentation (general)

  • EZH2機能喪失型MDSの創薬研究~あえて残ったH3K27me3に注目してみた~

    青山和正

    The 229th Scienc-ome (https://www.scienc-ome.com/), 

    2025.04
    , 

    Oral presentation (invited, special)

  • A novel regulatory mechanism for Polycomb repressive complexes (PRCs) : "PRC1-PRC2 complex model"

    青山和正, ポスター, 菊池敬, 田中祐貴, 田口想, 東孝輔, 中澤洋介, 多胡めぐみ

    第145回日本薬学会年会 (福岡) , 

    2025.03
    , 

    Poster presentation

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

  • EZH2機能喪失を伴う骨髄異形成症候群のがん幹細胞維持機構の解明と創薬標的分子の探索

    2025.04
    -
    2028.03

    公益財団法人小林財団, 第13回（令和6年度）研究助成, 青山和正, Principal investigator

  • 新規複合体「PRC1-PRC2複合体」の解析

    2025.04
    -
    2026.03

    徳島大学先端酵素学研究所, 2025年度共同研究 B-2細胞情報学分野 共同研究経費, Principal investigator

  • Identification of Drug Targets for EZH2 Loss-of-Function Myelodysplastic Syndromes

    2024.10
    -
    2026.08

    公益信託日本白血病研究基金, 研究助成事業（高久史磨賞）, Principal investigator

  • EZH2 機能喪失型の骨髄異形成症候群に対する新規創薬標的分子

    2024.09
    -
    2025.03

    公益信託日本白血病研究基金, 2024年度日本血液学会研究助成, Principal investigator

  • "残存H3K27me3"を標的とするEZH2 機能低下型MDS に対する創薬研究

    2024.04
    -
    2025.03

    慶應義塾大学, 福澤基金研究補助, Principal investigator

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Awards 【 Display / hide 】

  • 高久史磨賞

    青山和正, 2024.08, 公益信託日本白血病研究基金, Identification of Drug Targets for EZH2 Loss-of-Function Myelodysplastic Syndromes

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

  • 第12回 次世代を担う若手ファーマ・バイオフォーラム2013 優秀発表賞受賞

    2013.09, 日本薬学会生物系薬学部会, c-Abl によるヒストン脱アセチル化を介したクロマチン構造変換と核内 F-アクチン形成

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

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Other 【 Display / hide 】

  • 2025年01月

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    「ヒトiPS細胞の培養に関する技術研修」修了（国立研究開発法人理化学研究所 バイオリソース研究センター）：ヒトiPS細胞の培養に関する研修を受講し、主にオンフィーダーの培養技術を習得した。

  • 2024年06月

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    「BD FACSAria™ Basic」修了（BD Biosciences）：FACS ariaの使用法に関するトレーニングを２日間受講し、基礎技術を習得した。

  • 2018年10月

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    「Introduction to Microsurgery」修了（National Institute of Health(NIH) National Heart, Lung, and Blood Institute(NHLBI) Animal Program Division）：アメリカ留学中に動物の顕微鏡手術に関するトレーニングを受講して、基礎技術を習得した。

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Courses Taught 【 Display / hide 】

  • STUDY OF MAJOR FIELD: (HYGIENIC CHEMISTRY)

    2025

  • SEMINAR: (HYGIENIC CHEMISTRY)

    2025

  • RESEARCH FOR BACHELOR'S THESIS 1

    2025

  • PHARMACEUTICAL-ENGLISH SEMINAR

    2025

  • HYGIENIC CHEMISTRY AND PUBLIC HEALTH LABORATORY COURSE

    2025

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Educational Activities and Special Notes 【 Display / hide 】

  • ファカルティ・ディベロップメント（FD）参加 慶應義塾大学薬学部主催 内容「学生とのコミュニケーションに関わる問題」

    2025.03

  • 慶應大学薬学部 薬学共用試験 Computer-Based Testing (CBT) 追再試験 試験監督

    2025.02

  • 慶應大学薬学部 薬学共用試験 Computer-Based Testing (CBT) 追再試験 テストラン

    2025.02

  • 慶應大学薬学部 薬学共用試験 Computer-Based Testing (CBT) テストラン

    2025.01

  • 慶應大学薬学部 薬学共用試験 Computer-Based Testing (CBT) 試験監督 day1,2

    2025.01

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Academic Activities 【 Display / hide 】

  • 研究成果発表会採点委員 49th IMSUT (The Institute of Medical Science, the University of Tokyo) Founding Commemorative Symposium Flash Talks

    (東京大学医科学研究所 (Virtual)) , 

    2022.05

  • ポスター発表審査員Postbac Poster Day 2021 at National Institutes of Health(NIH)

    (National Institutes of Health (Virtual)) , 

    2021.04

  • ポスター発表審査員Postbac Poster Day 2020 at National Institutes of Health(NIH)

    (National Institutes of Health (Virtual)) , 

    2020.04

  • ポスター発表審査員Postbac Poster Day 2019 at National Institutes of Health(NIH)

    (National Institutes of Health(Bethesda, Maryland, USA)) , 

    2019.05

  • シンポジウムのオーガナイザー・司会 “Reproductive system and disease, Cancer epigenome, Public Symposium 2017”

    (千葉) , 

    2017.09

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Memberships in Academic Societies 【 Display / hide 】

  • 日本血液学会, 

    2022.03
    -
    Present

  • 日本生化学会, 

    2015.07
    -
    Present

  • 日本薬学会, 

    2010.12
    -
    Present
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Committee Experiences 【 Display / hide 】

  • 2024.04
    -
    2025.03

    2024年度 慶應大学薬学部 薬学共用試験 Objective Structured Clinical Examination (OSCE) 運営委員（調剤薬監査領域）

  • 2024.04
    -
    2025.03

    2024年度 慶應大学薬学部 学生実習委員

  • 2024.04
    -
    2025.03

    2024年度 慶應大学薬学部 薬学共用試験 Computer-Based Testing (CBT) 委員

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