片岡　圭亮 (カタオカ　ケイスケ)

Kataoka, Keisuke

写真a

所属（所属キャンパス）

医学部 内科学教室（血液） （信濃町）

職名

教授

HP

研究室住所

東京都新宿区信濃町35

研究室電話番号

03-3353-1211 (62385)

研究室FAX番号

03-3353-3515

外部リンク
このページの先頭へ▲

経歴 【 表示 ／ 非表示 】

  • 2005年04月
    -
    2007年03月

    国家公務員共済組合連合会虎の門病院

  • 2007年04月
    -
    2008年03月

    東京大学医学部附属病院, 血液・腫瘍内科, 専門研修医

  • 2009年04月
    -
    2012年03月

    日本学術振興会, 特別研究員(DC1)

  • 2012年04月
    -
    2012年06月

    東京大学医学部附属病院, 血液・腫瘍内科, 特任助教

  • 2012年07月
    -
    2013年10月

    東京大学大学院医学系研究科, 特任助教

全件表示 >>

このページの先頭へ▲

学歴 【 表示 ／ 非表示 】

  • 1999年04月
    -
    2005年03月

    東京大学, 医学部, 医学科

    大学, 卒業

  • 2009年04月
    -
    2012年03月

    東京大学, 大学院医学系研究科

    大学院, 修了, 博士

このページの先頭へ▲

学位 【 表示 ／ 非表示 】

  • 博士（医学）, 東京大学, 課程, 2012年03月

このページの先頭へ▲
 

研究分野 【 表示 ／ 非表示 】

  • ライフサイエンス / 腫瘍生物学 (Tumor biology)

  • ライフサイエンス / 血液、腫瘍内科学 (Hematology)

このページの先頭へ▲

研究キーワード 【 表示 ／ 非表示 】

  • 造血器腫瘍

  • 遺伝子解析

このページの先頭へ▲
 

論文 【 表示 ／ 非表示 】

  • PD-L1 expression on tumor or stromal cells of nodal cytotoxic T-cell lymphoma: A clinicopathological study of 50 cases

    Yamashita, D., Shimada, K., Kohno, K., Kogure, Y., Kataoka, K., Takahara, T., Suzuki, Y., Satou, A., Sakakibara, A., Nakamura, S., Asano, N. and Kato, S.

    Pathol Int 2020年05月

    ISSN  1440-1827

    　概要を見る

    Inhibitors of programmed cell-death 1 (PD-1) and programmed cell-death ligand 1 (PD-L1) have revolutionized cancer therapy. Nodal cytotoxic T-cell lymphoma (CTL) is characterized by a poorer prognosis compared to nodal non-CTLs. Here we investigated PD-L1 expression in 50 nodal CTL patients, with and without EBV association (25 of each). We identified seven patients (14%) with neoplastic PD-L1 (nPD-L1) expression on tumor cells, including three males and four females, with a median age of 66 years. One of the seven cases was TCRalphabeta type, three were TCRgammadelta type and three were TCR-silent type. Six of the seven cases exhibited a lethal clinical course despite multi-agent chemotherapy, of whom four patients died within one year of diagnosis. Morphological findings were uniform, with six cases showing centroblastoid appearance. Among nPD-L1(+) cases, two of three examined had structural variations of PD-L1 disrupting 3'-UTR region. Notably, all of the TCRgammadelta-type nodal CTL cases showed nPD-L1 or miPD-L1 positivity (3 and 10 cases, respectively). TCRgammadelta-type cases comprised 42% of nPD-L1(+) cases (P = 0.043 vs. PD-L1(-) ), and 35% of miPD-L1(+) cases (P = 0.037 vs. PD-L1(-) ). The results indicate that PD-L1(+) nodal CTL cases, especially of the TCRgammadelta type, are potential candidates for anti-PD-1/PD-L1 therapies.

  • LUBAC accelerates B-cell lymphomagenesis by conferring B cells resistance to genotoxic stress

    Jo, T., Nishikori, M., Kogure, Y., Arima, H., Sasaki, K., Sasaki, Y., Nakagawa, T., Iwai, F., Momose, S., Shiraishi, A., Kiyonari, H., Kagaya, N., Onuki, T., Shin-Ya, K., Yoshida, M., Kataoka, K., Ogawa, S., Iwai, K. and Takaori-Kondo, A.

    Blood 2020年04月

    ISSN  1528-0020

    　概要を見る

    Linear ubiquitin chain assembly complex (LUBAC) is a key regulator of NF-kB signaling. Activating single-nucleotide polymorphisms of HOIP, the catalytic subunit of LUBAC, are enriched in patients with activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL), and expression of HOIP which parallels LUBAC activity is elevated in ABC-DLBCL samples. Thus, to clarify the precise roles of LUBAC in lymphomagenesis, we generated a mouse model with augmented expression of HOIP in B cells. Interestingly, augmented HOIP expression facilitated DLBCL-like B-cell lymphomagenesis driven by MYD88-activating mutation. The developed lymphoma cells partly shared somatic gene mutations with human DLBCLs, with increased frequency of a typical AID mutation pattern. In vitro analysis revealed that HOIP overexpression protected B cells from DNA damage-induced cell death through NF-kB activation, and the analysis of human DLBCL database showed that expression of HOIP positively correlated with gene signatures representing regulation of apoptosis signaling, as well as NF-kB signaling. These results indicate that HOIP facilitates lymphomagenesis by preventing cell death and augmenting NF-kB signaling, leading to accumulation of AID-mediated mutations. Furthermore, a natural compound that specifically inhibits LUBAC was shown to suppress the tumor growth in a mouse transplantation model. Collectively, our data indicates that LUBAC is crucially involved in B-cell lymphomagenesis through protection against DNA damage-induced cell death, and is a suitable therapeutic target for B-cell lymphomas.

  • Combined Cohesin-RUNX1 Deficiency Synergistically Perturbs Chromatin Looping and Causes Myelodysplastic Syndromes

    Ochi, Y., Kon, A., Sakata, T., Nakagawa, M. M., Nakazawa, N., Kakuta, M., Kataoka, K., Koseki, H., Nakayama, M., Morishita, D., Tsuruyama, T., Saiki, R., Yoda, A., Okuda, R., Yoshizato, T., Yoshida, K., Shiozawa, Y., Nannya, Y., Kotani, S., Kogure, Y., Kakiuchi, N., Nishimura, T., Makishima, H., Malcovati, L., Yokoyama, A., Takeuchi, K., Sugihara, E., Sato, T. A., Sanada, M., Takaori-Kondo, A., Cazzola, M., Kengaku, M., Miyano, S., Shirahige, K., Suzuki, H. I. and Ogawa, S.

    Cancer Discov 2020年04月

    ISSN  2159-8290

    　概要を見る

    STAG2 encodes a cohesin component and is frequently mutated in myeloid neoplasms, showing highly significant comutation patterns with other drivers, including RUNX1. However, the molecular basis of cohesin-mutated leukemogenesis remains poorly understood. Here we show a critical role of an interplay between STAG2 and RUNX1 in the regulation of enhancer-promoter looping and transcription in hematopoiesis. Combined loss of STAG2 and RUNX1, which colocalize at enhancer-rich, CTCF-deficient sites, synergistically attenuates enhancer-promoter loops, particularly at sites enriched for RNA polymerase II and Mediator, and deregulates gene expression, leading to myeloid-skewed expansion of hematopoietic stem/progenitor cells (HSPC) and myelodysplastic syndromes (MDS) in mice. Attenuated enhancer-promoter loops in STAG2/RUNX1-deficient cells are associated with downregulation of genes with high basal transcriptional pausing, which are important for regulation of HSPCs. Downregulation of high-pausing genes is also confirmed in STAG2-cohesin-mutated primary leukemia samples. Our results highlight a unique STAG2-RUNX1 interplay in gene regulation and provide insights into cohesin-mutated leukemogenesis. SIGNIFICANCE: We demonstrate a critical role of an interplay between STAG2 and a master transcription factor of hematopoiesis, RUNX1, in MDS development, and further reveal their contribution to regulation of high-order chromatin structures, particularly enhancer-promoter looping, and the link between transcriptional pausing and selective gene dysregulation caused by cohesin deficiency.

  • TET2 haploinsufficiency alters reprogramming into induced pluripotent stem cells

    Secardin, L., Limia, C. E. G., di Stefano, A., Bonamino, M. H., Saliba, J., Kataoka, K., Rehen, S. K., Raslova, H., Marty, C., Ogawa, S., Vainchenker, W., Monte-Mor, Bdcr and Plo, I.

    Stem Cell Res 44   101755 2020年03月

    ISSN  1876-7753

    　概要を見る

    The discovery of the Ten-Eleven Translocation (TET) protein family was initiated by the identification of the MLL partner TET1, and of mutations in the TET2 gene in hematological malignancies including myeloproliferative neoplasms (MPN). TET1, 2 and 3 proteins hydroxylate 5-methylcytosine (5-mC) into 5-hydroxymethylcytosine (5-hmC) and further oxidize 5-hmC into 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC). Previous studies highlight the involvement of TET proteins in somatic cells reprogramming into induced pluripotent stem cells (iPSC), particularly Tet1 and 2 in mouse and TET1 in human. Here, we asked whether endogenous TET2 knockdown also displays this function. Using different shRNA against TET2, we provide evidence that TET2 strongly decreases the reprogramming of human hematopoietic progenitor cells into iPSC. Importantly, using 2 MPN patients, we observed that TET2 mutations affecting catalytic domain allowed iPSC generation. Instead, using another TET2 and TET3-mutated patient, we could only reprogram IPSC with TET3 mutation alone, suggesting that the type of TET2 mutation and/or the cooperation with TET3 mutations may alter the reprogramming activity. Altogether, this work highlights the importance of endogenous TET in the reprogramming process of human hematopoietic progenitors.

  • Blockade of EGFR improves responsiveness to PD-1 blockade in EGFR-mutated non-small cell lung cancer

    Sugiyama, E., Togashi, Y., Takeuchi, Y., Shinya, S., Tada, Y., Kataoka, K., Tane, K., Sato, E., Ishii, G., Goto, K., Shintani, Y., Okumura, M., Tsuboi, M. and Nishikawa, H.

    Sci Immunol 5 （ 43 ）  2020年01月

    ISSN  2470-9468

    　概要を見る

    The clinical efficacy of anti-PD-1 (programmed cell death-1) monoclonal antibody (mAb) against cancers with oncogenic driver gene mutations, which often harbor a low tumor mutation burden, is variable, suggesting different contributions of each driver mutation to immune responses. Here, we investigated the immunological phenotypes in the tumor microenvironment (TME) of epidermal growth factor receptor (EGFR)-mutated lung adenocarcinomas, for which anti-PD-1 mAb is largely ineffective. Whereas EGFR-mutated lung adenocarcinomas had a noninflamed TME, CD4(+) effector regulatory T cells, which are generally present in the inflamed TME, showed high infiltration. The EGFR signal activated cJun/cJun N-terminal kinase and reduced interferon regulatory factor-1; the former increased CCL22, which recruits CD4(+) regulatory T cells, and the latter decreased CXCL10 and CCL5, which induce CD8(+) T cell infiltration. The EGFR inhibitor erlotinib decreased CD4(+) effector regulatory T cells infiltration in the TME and in combination with anti-PD-1 mAb showed better antitumor effects than either treatment alone. Our results suggest that EGFR inhibitors when used in conjunction with anti-PD-1 mAb could increase the efficacy of immunotherapy in lung adenocarcinomas.

全件表示 >>

このページの先頭へ▲

競争的研究費の研究課題 【 表示 ／ 非表示 】

  • 悪性リンパ腫における遺伝子異常を基盤とした発症機構・分子病態の統合的解明

    2021年07月
    -
    2026年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 片岡 圭亮, 基盤研究(S), 補助金,  研究代表者

  • 悪性リンパ腫における遺伝子異常を基盤とした発症機構・分子病態の統合的解明

    2021年04月
    -
    2024年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 片岡 圭亮, 基盤研究(A), 補助金,  研究代表者

このページの先頭へ▲

受賞 【 表示 ／ 非表示 】

  • 日本医学会総会奨励賞 内科系最優秀奨励賞

    2019年04月

  • 日本医学会連合Rising Starリトリート優秀賞

    2019年03月

  • 荻村孝特別研究賞

    2018年10月

  • 科学技術分野の文部科学大臣表彰 若手科学者賞

    2017年04月

  • BMS Award

    2017年02月

全件表示 >>

このページの先頭へ▲
 

担当授業科目 【 表示 ／ 非表示 】

  • 化学療法学

    2024年度

  • 内科学特論

    2024年度

  • 臨床腫瘍学特論

    2024年度

  • 血液内科学臨床実習

    2024年度

  • 医学特別講義

    2024年度

全件表示 >>

このページの先頭へ▲
 

所属学協会 【 表示 ／ 非表示 】

  • 米国癌学会, 

    2020年
    -
    継続中

  • 日本臨床分子医学会, 

    2017年
    -
    継続中

  • 米国血液学会, 

    2016年
    -
    継続中

  • 日本リンパ網内系学会, 

    2015年
    -
    継続中

  • 日本HTLV-1学会, 

    2015年
    -
    継続中

全件表示 >>

このページの先頭へ▲