AIシステム医科学分野

Department of AI Systems Medicine

医療者の視点から見た課題に対し大規模データ取得・数理データ科学・生命科学実験による検証という三位一体研究によってアプローチします。また、ラボ内外の教育を重視することで将来の科学・医療界に大きな投資をしています。AIシステム医科学分野では独自のWebサイトも運営しておりますのであわせてご覧ください。

メンバー

清水秀幸

教授

大野聡

講師

麻生啓文

助教

古賀大介

特任研究員

研究プロジェクト

AI創薬

広大な化合物の「海」からほとんど手がかりなしに目的の化合物を「照らし出す」AI創薬システムLIGHTHOUSE (灯台) を開発 (Shimizu et al., 2022)し、いくつもの新薬を実験的に見つけたことで、NHKなどテレビ各社や朝日・読売新聞、ネットニュースに大きく取り上げられました。

現在はLIGHTHOUSEをさらに拡張させ、物理化学法則を取り込んだ創薬基盤プラットフォームの開発をしています。低分子医薬品だけでなく、中分子・抗体医薬といったより複雑な分子デザインにも挑戦を始めました。

大規模データ時代のシステムワイドな疾患研究

糖尿病やがんなどの多因子疾患では、単独の遺伝子や分子に原因を帰着させることができません。代謝物・タンパク質・RNAなどの多階層のデータを数理科学的に統合することで、多因子疾患の病態の包括的かつ定量的な理解を目指しています。 (Kodama, Oshikawa, Shimizu et al., 2020; Uematsu, Ohno, et al., iScience, 2022など)。

AIを使った臨床患者データ解析 (クリニカルインフォマティクス)

医師としての専門的な知見をベースにして、健康・疾患データならではの課題に対処するための解析手法・ツールの開発や、患者さんの層別化に関する研究を行っています。例えば乳がんの遺伝子発現データをAIで学習することで、23の遺伝子のみからTNM分類以上にステージを層別化する手法を開発 (Shimizu et al., 2019) し、NHKニュースや日経新聞で報道されました。

その他

これ以外にもさまざまな研究をしています。ぜひお問い合わせください。

最近の研究業績

2024

Sakuma T, Mukai Y, Yamaguchi A, Suganuma Y, Okamoto K, Furugen A, Narumi K, Ishikawa S, Saito Y,Kobayashi M. Monocarboxylate Transporters 1 and 2 Are Responsible for L-Lactate Uptake in Differentiated Human Neuroblastoma SH-SY5Y Cells. Biol. Pharm. Bull. 47(4):764-770, 2024 Kasai S , Shiomi A, Shimizu H, Aoba M, Kinugasa Y, Miura T, Uehara K, Watanabe J, Kawai K, Ajioka Y. Risk factors and development of machine learning diagnostic models for lateral lymph node metastasis in rectal cancer: a multicentre study. BJS Open, 2024
Konno Y, Uriu K, Chikata T, Takada T, Kurita JI, Ueda MT, Islam S, Yang Tan BJ, Ito J, Aso H, Kumata R, Williamson C, Iwami S, Takiguchi M, Nishimura Y, Morita E, Satou Y, Nakagawa S, Koyanagi Y, Sato K. Two-step evolution of HIV-1 budding system leading to pandemic in the human population. Cell Rep., 43(2), 113697, 2024
Bai Y, Morita K, Kokaji T, Hatano A, Ohno S, Egami R, Pan Y, Li D, Yugi K, Uematsu S, Inoue H, Inaba Y, Suzuki Y, Matsumoto M, Izumi Y, Bamba T, Hirayama A, Soga T, Kuroda S. iScience, 27(3):109121, 2024
岡田随象企画、川原田明徳, 大谷悠喜, 清水秀幸分担著書、医学のあゆみ増刊号「遺伝統計学の新潮流 ─新規創薬・個別化医療への挑戦」, 医歯薬出版 2024

2023

Oka T, Higa T, Sugahara O, Koga D, Nakayama S, Nakayama KI. Ablation of p57+ quiescent cancer stem cells suppresses recurrence after chemotherapy of intestinal tumors. Cancer Res., 2023
Kodama M, Toyokawa G, Sugahara O, Sugiyama S, Haratake N, Yamada Y, Wada R, Takamori S, Shimokawa M, Takenaka T, Tagawa T, Kittaka H, Tsuruda T, Tanaka K, Komatsu Y, Nakata K, Imado Y, Yamazaki K, Okamoto I, Oda Y, Takahashi M, Izumi Y, Bamba T, Shimizu H, Yoshizumi T, Nakayama KI. Modulation of host glutamine anabolism enhances the sensitivity of small cell lung cancer to chemotherapy. Cell Rep., 42(8):112899, 2023
Aso H, Ito J, Ozaki H, Kashima Y, Suzuki Y, Koyanagi Y, Sato K. Single-cell transcriptome analysis illuminating the characteristics of species-specific innate immune responses against viral infections. GigaScience, 12, 2023
Funasaki S, Hatano A, Nakatsumi H, Koga D, Sugahara O, Yumimoto K, Baba M, Matsumoto M, Nakayama KI. A stepwise and digital pattern of RSK phosphorylation determines the outcome of thymic selection. iScience 26 (9), 107552, 2023
Maehara H, Kokaji T, Hatano A, Suzuki Y, Matsumoto M, Nakayama KI, Egami R, Tsuchiya T, Ozaki H, Morita K, Shirai M, Li D, Terakawa A, Uematsu S, Hironaka K, Ohno S, Kubota H, Araki H, Miura F, Ito T, Kuroda S. DNA hypomethylation characterizes genes encoding tissue-dominant functional proteins in liver and skeletal muscle. Sci. Rep., 2023
大澤毅編、大野聡分担著書、実験医学増刊「マルチオミクス　データ駆動時代の疾患研究」. 羊土社 2023
「一家に一枚　ウイルス」製作チーム (小嶋将平、渡士幸一、渡辺登喜子、堀江真行、麻生啓文、多賀佳、川久保修介、塩野谷果歩) 製作監修. 学習資料「一家に1枚　ウイルス」文部科学省 2023
Hozumi H, Shimizu H. Bayesian network enables interpretable and state-of-the-art prediction of immunotherapy responses in cancer patients. PNAS Nexus. in press
Fujinuma S, Nakatsumi H, Shimizu H, Sugiyama S, Harada A, Goya T, Tanaka M, Kohjima M, Takahashi M, Izumi Y, Yagi M, Kang D, Kaneko M, Shigeta M, Bamba T, Ohkawa Y, Nakayama KI. FOXK1 promotes nonalcoholic fatty liver disease by mediating mTORC1-dependent inhibition of hepatic fatty acid oxidation. Cell Rep. in press.
清水秀幸編著. 実験医学別冊 Pythonで実践生命科学データの機械学習. 羊土社 2023

2022

Uematsu S, Ohno S, Tanaka KY, Hatano A, Kokaji T, Ito Y, Kubota H, Hironaka K, Suzuki Y, Matsumoto M, Nakayama KI, Hirayama A, Soga T, Kuroda S. Multi-omics-based label-free metabolic flux inference reveals obesity-associated dysregulatory mechanisms in liver glucose metabolism. iScience, 25(2), 103787. (2022)
Ohno S, Uematsu S, Kuroda S. Quantitative metabolic fluxes regulated by trans-omic networks. Biochem. J. 479(6), 787–804, 2022
Kokaji T, Eto M, Hatano A, Yugi K, Morita K, Ohno S, Fujii M, Hironaka K, Ito Y, Egami R, Uematsu S, Terakawa A, Pan Y, Maehara H, Li D, Bai Y, Tsuchiya T, Ozaki H, Inoue H, Kubota H, Suzuki Y, Hirayama A, Soga T, Kuroda S. In vivo transomic analyses of glucose-responsive metabolism in skeletal muscle reveal core differences between the healthy and obese states. Sci. Rep. 12(1), 1–19, 2022
Aso H, Ito J, Ozaki H, Kashima Y, Suzuki Y, Koyanagi Y, Sato K. Single-cell transcriptome analysis illuminating the characteristics of species-specific innate immune responses against viral infections. bioRxiv, 2022
Mise S, Matsumoto A, Shimada K, Hosaka T, Takahashi M, Ichihara K, Shimizu H, Shiraishi C, Saito D, Suyama M, Yasuda T, Ide T, Izumi Y, Bamba T, Kimura-Someya T, Shirouzu T, Miyata H, Ikawa M, and Nakayama KI. Kastor and Polluks polypeptides encoded by a single gene locus cooperatively regulate VDAC and spermatogenesis. Nature Commun. 2022
Shimizu H, Kodama M, Matsumoto M, Orba Y, Sasaki Y, Sato A, Sawa H, Nakayama KI. LIGHTHOUSE illuminates therapeutics for a variety of diseases including COVID-19. iScience 2022
Habara M, Sato Y, Goshima T, Sakurai M, Imai H, Shimizu H, Katayama Y, Hanaki S, Masaki T, Morimoto M, Nishikawa S, Toyama T, Shimada M. PNAS 2022
Terakawa A, Hu Y, Kokaji T, Yugi K, Morita K, Ohno S, Pan Y, Bai Y, Parkhitko AA, Ni X, Asara JM, Bulyk ML, Perrimon N, Kuroda S. iScience 2022

2021

Aso H, Nagaoka S, Kawakami, Ito J, Islam S, Tan BJY, Nakaoka S, Ashizaki K, Shirogushi K, Suzuki Y, Satou Y, Koyanagi Y, Sato K. Multiomics investigation revealing comprehensive characteristics of HIV-1-infected cells in vivo. Cell Rep., 32 (2), 107887, 2020
Kosugi Y, Uriu K, Suzuki N, Yamamoto K, Nagaoka S, Kimura I, Konno Y, Aso H, Willett BJ, Kobayashi T, Koyanagi Y, Ueda MT, Ito J, Sato K. A comprehensive investigation on the interplay between feline APOBEC3Z3 proteins and feline immunodeficiency virus Vif proteins. J. Virol., 95(13):e0017821, 2021
Ichihara K, Matsumoto A, Nishida H, Kito Y, Shimizu H, Shichino Y, Iwasaki S, Imami K, Ishihama Y, Nakayama KI. Combinatorial analysis of translation dynamics reveals eIF2 dependence of translation initiation at near-cognate codons. Nucleic Acids Res. 2021
Shimizu H, Nakayama KI. A universal molecular prognostic score for gastrointestinal tumors. NPJ Genom. Med. 2021
Egami R, Kokaji T, Hatano A, Yugi K, Eto M, Morita K, Ohno S, Fujii M, Hironaka K, Uematsu S, Terakawa A, Bai Y, Pan Y, Tsuchiya T, Ozaki H, Inoue H, Uda S, Kubota H, Suzuki Y, Matsumoto M, Nakayama KI, Hirayama A, Soga T, Kuroda S. iScience 2021

2020

Hwang YS, Suzuki S, Saita Y, Ito J, Sakata Y, Aso H, Sato K, Hermann BP, Sasaki K. Reconstitution of prospermatogonial specification in vitro from human induced pluripotent stem cells. Nature Commun.,11(1), 5656, 2020
Nakano Y, Keisuke Y, Ueda MT, Soper A, Konno Y, Kimura I, Uriu K, Kumata R, Aso H, Misawa N, Nagaoka S, Shimizu S, Mitsumune K, Kosugi Y, Juarez-Fernandez G, Ito J, Nakagawa S, Ikeda T, Koyanagi Y, Harris RS, Sato K. A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans. PLoS Pathog., 16(9), e1008812, 2020
Onoyama I, Nakayama S, Shimizu H, Nakayama KI. Loss of Fbxw7 impairs development of and induces heterogeneous tumor formation in the mouse mammary gland. Cancer Res. 2020
Shimizu H, Nakayama KI. Artificial intelligence in oncology. Cancer Sci. 2020
Yamauchi Y, Nita A, Nishiyama M, Muto Y, Shimizu H, Nakatsumi H, Nakayama KI. Skp2 contributes to cell cycle progression in trophoblast stem cells and to placental development. Genes Cells. 2020
Oshikawa K, Matsumoto M, Kodama M, Shimizu H, Nakayama KI. A fail-safe system to prevent oncogenesis by senescence is targeted by SV40 small T antigen. Oncogene 2020
Kodama M, Oshikawa K, Shimizu H, Yoshioka S, Takahashi M, Izumi Y, Bamba T, Tateishi C, Tomonaga T, Matsumoto M, Nakayama KI. A shift in glutamine nitrogen metabolism contributes to malignant progression of cancer. Nature Commun. 2020
Kokaji T, Hatano A, Ito Y, Yugi K, Eto M, Morita K, Ohno S, Fujii M, Hironaka K, Egami R, Terakawa A, Tsuchiya T, Ozaki H, Inoue H, Uda S, Kubota H, Suzuki Y, Ikeda K, Arita M, Matsumoto M, Nakayama K.I, Hirayama A, Soga T, Kuroda S. Science Signaling 2020
Ohno S, Quek L-E, Krycer JR, Yugi K, Hirayama A, Ikeda S, Shoji F, Suzuki K, Soga T, James DE, Kuroda S. iScience 2020
Quek L-E, Krycer JR, Ohno S, Yugi K, Fazakerley DJ, Scalzo R, Elkington SD, Dai Z, Hirayama A, Ikeda S, Shoji F, Suzuki K, Locasale JW, Soga T, James DE, Kuroda S. iScience 2020

〜2019

Aso H, Ito J, Koyanagi Y, Sato K. Comparative Description of the Expression Profile of Interferon- stimulated Genes in Multiple Cell Lineages Targeted by HIV-1 Infection. Front. Microbiol., 10, 429, 2019
Shimizu H, Nakayama KI. A 23 gene-based molecular prognostic score precisely predicts overall survival of breast cancer patients. EBioMedicine 2019
Muto Y, Moroishi T, Ichihara K, Nishiyama M, Shimizu H, Eguchi H, Moriya K, Koike K, Mimori K, Mori M, Katayama Y, Nakayama KI. Disruption of FBXL5-mediated cellular iron homeostasis promotes liver carcinogenesis. J. Exp. Med. 2019
Shimizu H, Takeishi S, Nakatsumi H, Nakayama KI. Prevention of cancer dormancy by Fbxw7 ablation eradicates disseminated tumor cells. JCI Insight 2019
Krycer JR, Yugi K, Hirayama A, Fazakerley DJ, Quek L-E, Scalzo R, Ohno S, Hodson MP, Ikeda S, Shoji F, Suzuki K, Domanova W, Parker LB, Nelson ME, Humphrey SJ, Turner N, Hoehn KL, Cooney GJ, Soga T, Kuroda S, James DE. Cell Reports 2017
Sano T, Kawata K, Ohno S, Yugi K, Kakuda H, Kubota H, Uda S, Fujii M, Kunida K, Hoshino D, Hatano A, Ito Y, Sato M, Suzuki Y, Kuroda S. Science Signaling 2016
Tokuyama K, Ohno S, Yoshikawa K, Hirasawa T, Tanaka S, Furusawa C, Shimizu H. Microb. Cell Fact. 2014
Nakashima N, Ohno S, Yoshikawa K, Shimizu H, Tamura T. Appl. Environ. Microbiol. 2014
Ohno S, Shimizu H, Furusawa C. Bioinformatics 2014
Ohno S, Furusawa C, Shimizu H. J. Biosci. Bioeng. 2013
Saiki Y, Yoshino Y, Fujimura H, Manabe T, Kudo Y, Shimada M, Mano N, Nakano T, Lee Y, Shimizu S, Oba S, Fujiwara S, Shimizu H, Chen N, Nezhad ZK, Jin G, Fukushige S, Sunamura M, Ishida M, Motoi F, Egawa S, Unno M, Horii A. DCK is frequently inactivated in acquired gemcitabine-resistant human cancer cells. Biochem. Biophys. Res. Commun. 2012
Shimizu H, Horii A, Sunamura M, Motoi F, Egawa S, Unno M, Fukushige S. Identification of epigenetically silenced genes in human pancreatic cancer by a novel method “microarray coupled with methyl-CpG targeted transcriptional activation” (MeTA-array). Biochem. Biophys. Res. Commun. 2011