Division of Endocrinology, Metabolism and Signal Research
・SHIBATA LAB website https://shibataxlab.com/
・Google Scholar https://scholar.google.co.jp/citations?user=cM4dRzEAAAAJ&hl=ja
1. Elucidation of the mechanism underlying DNA repair pathway choice
2. Investigating the molecular mechanism of DNA damage dependent immune response
3. Visualization of DNA damage in the context of chromatin structure by 3D-SIM
1. DNA repair、DNA double break、DNA repair pathway choice、Transcription-associated repair、Mutation、Drug screen for DNA repair pathway manipulation
2. Fluorescence imaging analysis, Super resolution imaging, 3D-SIM, AI imaging
3. Anti-PD-1/PD-L1 therapy, PD-L1 expression, Precision medicine, Radiotherapy, Heavy ion particle therapy, Chemotherapy, Hypoxia
Our laboratory aims to elucidate the molecular mechanism underlying DNA double-strand break (DSB) repair, which is critical for maintaining genome integrity. Defects in DSB repair lead to severe mutations, including deletions and chromosomal translocations, which cause cell death. Introducing such severe mutations is important for killing cancer cells via radio/chemotherapy. We are currently investigating the interplay between non-homologous end joining (NHEJ) and homologous recombination (HR), which are major DSB repair pathways. We have recently attempted to visualize a repair event at a single DSB using super-resolution microscope 3D structured-illumination microscopy (SIM). We have also conducted several ongoing projects with radiation oncologists on combined radio- and immunotherapy, such as anti-PD-1/PD-L1 therapy.
(for all publications, please see http://shibatalab.com/publication)
Tiara Bunga Mayang Permata, Yoshihiko Hagiwara, Hiro Sato, Takaaki Yasuhara, Takahiro Oike, Soehartati Gondhowiardjo, Kathryn D. Held, Takashi Nakano & Atsushi Shibata*.
Base excision repair regulates PD-L1 expression in cancer cells.
Oncogene, 10.1038/s41388-019-0733-6, 2019.
Takaaki Yasuhara#*, Reona Kato#, Yoshihiko Hagiwara, Bunsyo Shiotani, Motohiro Yamauchi, Shinichiro Nakada, Atsushi Shibata* and Kiyoshi Miyagawa*.
Human Rad52 Promotes XPG-Mediated R-loop Processing to Initiate Transcription-Associated Homologous Recombination Repair.
Cell, 175 (2):558-570, 2018. (Citation 7, 2019)
Hiro Sato, Atsuko Niimi, Takaaki Yasuhara, Tiara Bunga Mayang Permata, Yoshihiko Hagiwara, Mayu Isono, Endang Nuryadi, Ryota Sekine, Takahiro Oike, Sangeeta Kakoti, Yuya Yoshimoto, Kathryn D. Held, Yoshiyuki Suzuki, Koji Kono, Kiyoshi Miyagawa, Takashi Nakano and Atsushi Shibata*.
DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells
Nature Communications, 8(1):1751, 2017. (Citation 35, 2019)
Mayu Isono, Atsuko Niimi, Takahiro Oike, Yoshihiko Hagiwara, Hiro Sato, Ryota Sekine, Yukari Yoshida, Shin-Ya Isobe, Chikashi Obuse, Ryotaro Nishi, Elena Petricci, Shinichiro Nakada, Takashi Nakano and Atsushi Shibata*.
BRCA1 directs the repair pathway to homologous recombination by promoting 53BP1 dephosphorylation.
Cell Reports, 18(2):520-532, 2017. (Citation 32, 2019)
Ronja Biehs, Monika Steinlage, Olivia Barton, Szilvia Juhasz, Julia Kunzel, Julian Spies, Atsushi Shibata*, Penny Jeggo* and Markus Lobrich*.
DNA Double-Strand Break Resection Occurs during Non-homologous End Joining in G1 but Is Distinct from Resection during Homologous Recombination.
Molecular Cell, S1097-2765(16)30854-1, 2017. (Citation 65, 2019)
Atsushi Shibata, Davide Moiani, Andrew S. Arvai, Jefferson Perry, Shane M. Harding, Marie-Michelle Genois, Ranjan Maity, Sari van Rossum-Fikkert, Aryandi Kertokalio, Filippo Romoli, Amani Ismail, Ermal Ismalaj, Elena Petricci, Matthew J. Neale, Robert G. Bristow, Jean-Yves Masson, Claire Wyman, Penny A. Jeggo, John A. Tainer.
DNA Double Strand Break Repair Pathway Choice Is Directed by Distinct MRE11 Nuclease Activities.
Molecular Cell, 53 (1), 7-18, 2014. (Citation 260, 2019)
Atsushi Shibata, Sandro Conrad, Julie Birraux, Verena Geuting, Olivia Barton, Amani Ismail, Andreas Kakarougkas, Katheryn Meek, Gisela Taucher-Scholz, Markus Löbrich and Penny A Jeggo.
Factors determining DNA double-strand break repair pathway choice in G2 phase.
EMBO J, 30(6):1079-92, 2011. (Citation 340, 2019)
2020 The Japanese Radiation Research Society, Incentive Award
2017 The Japanese Radiation Research Society, Incentive Award
2017 The 60th Annual Meeting of the Japanese Radiation Research Society, Best Presentation Award
2017 The 24th DNA replication, recombination and repair workshop, Young Presentation Award
2012 Poster prize, Joint British Association for Cancer Research-Gray Institute
2010 Highly rated poster presentations, The AACR 101st Annual Meeting
・Google Scholar https://scholar.google.co.jp/citations?user=yLcLc1UAAAAJ&hl=ja
1. Investigation of the role of 53BP1 in DSB repair pathway choice
2. Education of DNA damage signaling for cancer immune response
Yuki Uchihara, Reiko Komori, Kenji Tago, Hiroomi Tamura, Megumi Funakoshi-Tago.
Methotrexate significantly induces apoptosis by inhibiting STAT3 activation in NPM-ALK-positive ALCL cells, Biochemical Pharmacology, 170:113666, 2019
Yuki Uchihara, Tomoyuki Ohe, Tadahiko Mashino, Takayuki Kidokoro, Kenji Tago, Hiroomi Tamura, Megumi Funakoshi-Tago.
N-Acetyl cysteine prevents activities of STAT3 inhibitors, Stattic and BP-1-102 independently of its antioxidant properties, Pharmacological Reports, 71(6):1067-1078, 2019
Yuki Uchihara, Kenji Tago, Hidetoshi Taguchi, Yuji Narukawa, Fumiyuki Kiuchi, Hiroomi Tamura, Megumi Funakoshi-Tago.
Taxodione induces apoptosis in BCR-ABL-positive cells through ROS generation, Biochemical Pharmacology, 154:357-372, 2018
Yuki Uchihara, Takayuki Kidokoro, Kenji Tago, Tadahiko Mashino, Hiroomi Tamura, Megumi Funakoshi-Tago.
A major component of vitamin E, α-tocopherol inhibits the anti-tumor activity of crizotinib against cells transformed by EML4-ALK, European Journal of Pharmacology, 825:1-9, 2018
Yuki Uchihara, Fumihito Ueda, Kenji Tago, Yosuke Nakazawa, Tomoyuki Ohe, Tadahiko Mashino, Shigenobu Yokota, Tadashi Kasahara, Hiroomi Tamura, Megumi Funakoshi-Tago.
Alpha-tocopherol attenuates the anti-tumor activity of crizotinib against cells transformed by NPM-ALK, PLoS One, 12(8):e0183003, 2017
Yuki Uchihara, Ken-ichiro Tanaka, Teita Asano, Fumiya Tamura, Tohru Mizushima.
Superoxide dismutase overexpression protects against glucocorticoid-induced depressive-like behavioral phenotypes in mice,
Biochemical and Biophysical Research Communications, 469(4):873-877, 2016