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Fujita, Hiroaki
Graduate School of Medicine, Medicine Program-Specific Senior Lecturer/Program-Specific Junior Associate Professor
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Last Updated :2025/04/29
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Last Updated :2025/04/29
Research
Research Topics, Overview of the research
Research Topics
過剰鉄によるフェロトーシス制御因子の解明Overview of the research
鉄は容易に電子を授受する性質から多くの酸化還元酵素の活性中心として機能する生体に必須の微量金属であるが、一方で過剰に存在すればフリーラジカルを発生し、毒性を発揮する。特に近年、鉄による脂質過酸化により惹起される新規細胞死フェロトーシスが報告され、鉄毒性に注目が集まっている。フェロトーシスはがんや虚血性疾患との関連から、精力的に解析されているが、そのメカニズム解析で進んでいるのはグルタチオン代謝系などのフェロトーシス抑制系であり、フェロ(鉄)+トーシス(死)という名称とは相反して鉄毒性の観点からのメカニズム解析は進んでいない。未開拓の分野である過剰鉄依存的フェロトーシスの全容を明らかにするため、上記システムを破壊し、鉄添加のみでフェロトーシス様の細胞死が惹起される細胞をCRISPR/Cas9技術により作成した。
さらに、作成した細胞で全遺伝子を対象としたCRISPRスクリーニングを行い、制御遺伝子の網羅的解析を行った。その結果、既知のフェロトーシス制御因子に加え多数の新規フェロトーシス促進・抑制因子を同定している。現在、それら因子の解析を通し、鉄の視点からフェロトーシス全容を理解するとともに、発がんを含めた生理的役割の解明を進めている。
Research Areas
Papers
- Synergistic involvement of the NZF domains of the LUBAC accessory subunits HOIL-1L and SHARPIN in the regulation of LUBAC functionYusuke Toda; Hiroaki Fujita; Koshiki Mino; Takuto Koyama; Seiji Matsuoka; Toshie Kaizuka; Mari Agawa; Shigeyuki Matsumoto; Akiko Idei; Momoko Nishikori; Yasushi Okuno; Hiroyuki Osada; Minoru Yoshida; Akifumi Takaori-Kondo; Kazuhiro IwaiCell Death & Disease, 11 Nov. 2024
- PRDX6 augments selenium utilization to limit iron toxicity and ferroptosis.Hiroaki Fujita; Yu-Ki Tanaka; Seiryo Ogata; Noriyuki Suzuki; Sota Kuno; Uladzimir Barayeu; Takaaki Akaike; Yasumitsu Ogra; Kazuhiro IwaiNature structural & molecular biology, 12 Jun. 2024
- A de novo dominant-negative variant is associated with OTULIN-related autoinflammatory syndrome.Yukiko Takeda; Masahiro Ueki; Junpei Matsuhiro; Erik Walinda; Takayuki Tanaka; Masafumi Yamada; Hiroaki Fujita; Shunichiro Takezaki; Ichiro Kobayashi; Sakura Tamaki; Sanae Nagata; Noriko Miyake; Naomichi Matsumoto; Mitsujiro Osawa; Takahiro Yasumi; Toshio Heike; Fumiaki Ohtake; Megumu K Saito; Junya Toguchida; Junko Takita; Tadashi Ariga; Kazuhiro IwaiThe Journal of experimental medicine, 03 Jun. 2024
- HOIL-1L deficiency induces cell cycle alteration which causes immaturity of skeletal muscle and cardiomyocytes.Kentaro Akagi; Shiro Baba; Hiroaki Fujita; Yasuhiro Fuseya; Daisuke Yoshinaga; Hirohito Kubota; Eitaro Kume; Fumiaki Fukumura; Koichi Matsuda; Takayuki Tanaka; Takuya Hirata; Megumu K Saito; Kazuhiro Iwai; Junko TakitaScientific reports, 17 Apr. 2024
- Iron-induced NCOA4 condensation regulates ferritin fate and iron homeostasis.Sota Kuno; Hiroaki Fujita; Yu-Ki Tanaka; Yasumitsu Ogra; Kazuhiro IwaiEMBO reports, 04 May 2022
- The HOIL-1L ligase modulates immune signalling and cell death via monoubiquitination of LUBAC.Yasuhiro Fuseya; Hiroaki Fujita; Minsoo Kim; Fumiaki Ohtake; Akira Nishide; Katsuhiro Sasaki; Yasushi Saeki; Keiji Tanaka; Ryosuke Takahashi; Kazuhiro IwaiNature cell biology, Jun. 2020, Peer-reviewed
- Cooperative Domain Formation by Homologous Motifs in HOIL-1L and SHARPIN Plays A Crucial Role in LUBAC StabilizationHiroaki Fujita; Akira Tokunaga; Satoshi Shimizu; Amanda L. Whiting; Francisco Aguilar-Alonso; Kenji Takagi; Erik Walinda; Yoshiteru Sasaki; Taketo Shimokawa; Tsunehiro Mizushima; Izuru Ohki; Mariko Ariyoshi; Hidehito Tochio; Federico Bernal; Masahiro Shirakawa; Kazuhiro IwaiCell Reports, 24 Apr. 2018, Peer-reviewed
- Differential Involvement of the Npl4 Zinc Finger Domains of SHARPIN and HOIL-1L in Linear Ubiquitin Chain Assembly Complex-Mediated Cell Death ProtectionSatoshi Shimizu; Hiroaki Fujita; Yoshiteru Sasaki; Tatsuaki Tsuruyama; Kazuhiko Fukuda; Kazuhiro IwaiMOLECULAR AND CELLULAR BIOLOGY, May 2016, Peer-reviewed
- Crystal structure of the N-myristoylated lipopeptide-bound MHC class I complexDaisuke Morita; Yukie Yamamoto; Tatsuaki Mizutani; Takeshi Ishikawa; Juri Suzuki; Tatsuhiko Igarashi; Naoki Mori; Takashi Shiina; Hidetoshi Inoko; Hiroaki Fujita; Kazuhiro Iwai; Yoshimasa Tanaka; Bunzo Mikami; Masahiko SugitaNATURE COMMUNICATIONS, Jan. 2016, Peer-reviewed
- Immunoblot analysis of linear polyubiquitination of NEMO.Sasaki Y; Fujita H; Nakai M; Iwai KMethods in molecular biology (Clifton, N.J.), 2015, Peer-reviewed
- Linear ubiquitin chains: NF-kappa B signalling, cell death and beyondKazuhiro Iwai; Hiroaki Fujita; Yoshiteru SasakiNATURE REVIEWS MOLECULAR CELL BIOLOGY, Aug. 2014, Peer-reviewed
- The linear ubiquitin assembly complex (LUBAC) is essential for NLRP3 inflammasome activationMary A. Rodgers; James W. Bowman; Hiroaki Fujita; Nicole Orazio; Mude Shi; Qiming Liang; Rina Amatya; Thomas J. Kelly; Kazuhiro Iwai; Jenny Ting; Jae U. JungJOURNAL OF EXPERIMENTAL MEDICINE, Jun. 2014, Peer-reviewed
- Mechanism Underlying I kappa B Kinase Activation Mediated by the Linear Ubiquitin Chain Assembly ComplexHiroaki Fujita; Simin Rahighi; Mariko Akita; Ryuichi Kato; Yoshiteru Sasaki; Soichi Wakatsuki; Kazuhiro IwaiMOLECULAR AND CELLULAR BIOLOGY, Apr. 2014, Peer-reviewed
- Suppression of LUBAC-mediated linear ubiquitination by a specific interaction between LUBAC and the deubiquitinases CYLD and OTULINTsuyoshi Takiuchi; Tomoko Nakagawa; Hironari Tamiya; Hiroaki Fujita; Yoshiteru Sasaki; Yasushi Saeki; Hiroyuki Takeda; Tatsuya Sawasaki; Alexander Buchberger; Tadashi Kimura; Kazuhiro IwaiGENES TO CELLS, Mar. 2014, Peer-reviewed
- A non-canonical UBA-UBL interaction forms the linear-ubiquitin-chain assembly complex.Hirokazu Yagi; Kazuhiro Ishimoto; Takeshi Hiromoto; Hiroaki Fujita; Tsunehiro Mizushima; Yoshinori Uekusa; Maho Yagi-Utsumi; Eiji Kurimoto; Masanori Noda; Susumu Uchiyama; Fuminori Tokunaga; Kazuhiro Iwai; Koichi KatoEMBO reports, 01 May 2012, Peer-reviewed
- Specific recognition of linear ubiquitin chains by the Npl4 zinc finger (NZF) domain of the HOIL-1L subunit of the linear ubiquitin chain assembly complexYusuke Sato; Hiroaki Fujita; Azusa Yoshikawa; Masami Yamashita; Atsushi Yamagata; Stephen E. Kaiser; Kazuhiro Iwai; Shuya FukaiPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Dec. 2011, Peer-reviewed
Misc.
- 直鎖型ユビキチンリガーゼLUBACの安定化機構の構造基盤研究徳永暉; 藤田宏明; WALINDA Erik; 大木出; 有吉眞理子; 杤尾豪人; 岩井一宏; 白川昌宏日本分子生物学会年会プログラム・要旨集(Web), 2018
- 多彩な自己炎症性疾患を紐解く Linear ubiquitin assembly complexとOTULINによる炎症と細胞死の制御 OTULIN-related autoinflammatory syndrome患者の解析を通して植木 将弘; 松廣 淳平; 竹崎 俊一郎; 藤田 宏明; 三宅 紀子; 戸澤 雄介; 山田 雅文; 小林 一郎; 松本 直通; 有賀 正; 岩井 一宏; 真部 淳日本小児リウマチ学会総会・学術集会プログラム・抄録集, Oct. 2019
- 直鎖状ポリユビキチン鎖形成を担うE3リガーゼ複合体における非典型的なUBA-UBL相互作用矢木宏和; 石本和大; 廣本武史; 藤田宏明; 水島恒裕; 水島恒裕; 植草義徳; 矢木真穂; 栗本英治; 栗本英治; 野田勝紀; 内山進; 徳永文稔; 徳永文稔; 岩井一宏; 岩井一宏; 加藤晃一; 加藤晃一日本蛋白質科学会年会プログラム・要旨集, 2012
- Linear polyubiquitin chain regulates immune response and inflammation藤田 宏明; 岩井 一宏医学のあゆみ, 10 Nov. 2012
- ユビキチンシステムが切り開く新たな生命現象 LUBACアクセサリー分子SHARPINとHOIL-1Lがプログラム細胞死抑制において果たす機能的差異の解析清水 覚司; 藤田 宏明; 岩井 一宏日本生化学会大会・日本分子生物学会年会合同大会講演要旨集, Dec. 2015
- LUBACリガーゼ形成における相同性の高いHOIL-1L、SHARPINのUBLの機能的差異藤田 宏明; 清水 覚司; 徳永 暉; Walinda Erik; 高木 賢治; 水島 恒裕; 栃尾 豪人; 岩井 一宏日本生化学会大会・日本分子生物学会年会合同大会講演要旨集, Dec. 2015
Presentations
- Mechanisms underlying iron-induced ferroptosis: possibile involvement of selenium metabolismHiroaki FujitaThe 1st international G-RE-XS Conference, 31 Mar. 2024, Invited
- 鉄依存性フェロトーシスの制御メカニズム解明藤田宏明日本生化学会, 01 Nov. 2023
- 鉄誘導性フェロトーシスの制御メカニズム解明藤田宏明1. メタルバイオサイエンス研究会, 19 Oct. 2022, Invited
- 過剰鉄によるフェロトーシス制御因子の解明藤田宏明2. 日本生化学会, 03 Nov. 2021
- Mathematical modeling of biological systems that regulate cell survival and deathHiroaki Fujita1. 数理シグナル 第一回国際シンポジウム, 02 Feb. 2019
- LUBAC安定化機構の解明と応用藤田 宏明医科研若手シンポジウム, 31 Jan. 2019, Invited
- Cooperative domain formation by homologous motifs in HOIL-1L and SHARPIN plays crucial roles in LUBAC stabilizationHiroaki Fujita第41回日本分子生物学会, 28 Nov. 2018
- Cooperative domain formation by homologous motifs in HOIL-1L and SHARPIN plays crucial roles in LUBAC stabilizationHiroaki Fujita第91回日本生化学会, 24 Sep. 2018
- Crystal structure of trimeric LUBAC reveals essential role of a novel HOIL-1L-SHARPIN interaction in LUBAC formation and functionFujita, H; Tokunaga A; Iwai, K第40回日本分子生物学会 シンポジウム, 09 Dec. 2017
- Crucial roles of unexpected interaction between subunits of LUBAC ubiquitin ligase in NF-kappaB and cell death藤田 宏明第9回シグナルネットワーク, 10 Jun. 2017
- Crucial roles of unexpected interaction between subunits of LUBAC ubiquitin ligase in NF-kappaB and cell deathHiroaki Fujita第39回日本分子生物学会 シンポジウム, 01 Dec. 2016
- Novel insights into linear ubiquitin chain assembly complex formationHiroaki Fujita2. 2016 Keystone Symposia Conference X3: Ubiquitin Signaling, 14 Mar. 2016
- 直鎖状ポリユビキチン鎖によるIKK複合体活性化メカニズムの解析藤田 宏明日本分子生物学会, 26 Nov. 2014
- LUBACによるIKK複合体活性化メカニズムの解析藤田 宏明細胞生物学会, 11 Jun. 2014
Books and Other Publications
- フェロトーシスとセレン代謝藤田宏明週刊 医学のあゆみ, Jul. 2024
- 直鎖状ポリユビキチン鎖による細胞機能制御藤田 宏明, Joint work, 分子から見た新しいシグナリング機構シグナリング研究2015(羊土社), Jun. 2015, Not refereed
- 直鎖状ポリユビキチン鎖による免疫・炎症反応の制御藤田 宏明, Joint work医学のあゆみ(医歯薬出版社), 2012, Not refereed
External funds: Kakenhi
- 過剰鉄によるフェロトーシス惹起メカニズムの解明Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)Complex systemsKyoto University藤田 宏明From 01 Apr. 2020, To 31 Mar. 2022, Granted鉄依存性細胞死;フェロトーシス;鉄
- 鉄濃度依存的なフェリチンのオートファジー経路選択性の解析Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)Biological SciencesKyoto University藤田 宏明From 01 Apr. 2020, To 31 Mar. 2022, Project Closedフェリチン;NCOA4;相分離;鉄;フェリチノファジー;オートファジー
- Elucidation of the mechanisms of cell survival and death by linear ubiquitin chainsGrant-in-Aid for Scientific Research (C)Basic Section 44010:Cell biology-relatedKyoto UniversityHiroaki FujitaFrom 01 Apr. 2019, To 31 Mar. 2022, Project ClosedLUBAC;ユビキチン;細胞死;直鎖状ユビキチン鎖
- Elucidation of cell death regulation mechanisms and physiological significance by HOIL-1LGrant-in-Aid for Young Scientists (B)Kyoto UniversityHiroaki FujitaFrom 01 Apr. 2017, To 31 Mar. 2019, Project ClosedLUBAC;細胞死;直鎖状ユビキチン鎖;ユビキチン;直鎖状ポリユビキチン鎖;HOIL-1L
- 細胞の生存と死を決定する制御システムの数理モデル化Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)Complex systemsKyoto University藤田 宏明From 01 Apr. 2017, To 31 Mar. 2019, Project ClosedNF-kBシグナル;細胞死;数理モデル;LUBAC;ユビキチン;NF-kB;直鎖状ポリユビキチン鎖
- Elucidating the mechanisms underlying linear ubiquitin chains-mediated cell death protectionGrant-in-Aid for Young Scientists (B)Kyoto UniversityHiroaki FujitaFrom 01 Apr. 2015, To 31 Mar. 2017, Project Closed細胞死;LUBAC;直鎖状ポリユビキチン鎖
- 鉄誘導性フェロトーシス惹起機構の解明Grant-in-Aid for Scientific Research (C)Basic Section 44010:Cell biology-relatedKyoto University藤田 宏明From 01 Apr. 2022, To 31 Mar. 2025, Grantedフェロトーシス;鉄;細胞死
- 鉄誘導性フェロトーシスを制御する新たな生命金属動態の解明Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)Complex systemsKyoto University藤田 宏明From 01 Apr. 2022, To 31 Mar. 2024, Grantedフェロトーシス;鉄;セレン
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Last Updated :2025/04/29
Education
Teaching subject(s)
- From 01 Apr. 2024, To 31 Mar. 2025Laboratory Course in PhysiologyFall
- From 01 Apr. 2024, To 31 Mar. 2025PhysiologyFall
- From 01 Apr. 2023, To 31 Mar. 2024Laboratory Course in PhysiologyFall
- From 01 Apr. 2023, To 31 Mar. 2024PhysiologyFall
- From Apr. 2016, To Mar. 2017Fundamental Chemical ExperimentsFall, 全学共通科目
- From Apr. 2015, To Mar. 2022Physiology practicalFall, 医学部
- From Apr. 2019, To Mar. 2022PhysiologyFall, 医学部
