東京大学アイソトープ総合センター Isotope Science Center,The University of Tokyo

教授 秋光 信佳

教授  秋光 信佳

薬学系研究科兼担

統括主任者

出身地:福岡

専門分野 ⟩⟩
放射線影響学、放射線イメージング
研究内容 ⟩⟩

放射線をツールとして生命現象を解明し、操作する

(1) 放射線等の外的ストレスに対する細胞応答の分子機構の解明と応用

 放射線を含めた多様な外的ストレスに対して適切に応答することで、生物は長い進化の歴史を生き延びてきました。このストレスに応答する仕組みの発達がそれぞれの種の特徴を形作ってきたといっても過言ではありません。私たちの研究室では、放射線をはじめとして様々なストレスに対する細胞レベルの応答(特に遺伝子発現)の分子機構を解明することを目指しています。特に、長鎖ノンコーディングRNAと呼ばれる一群の機能性RNAに着目したストレス応答研究を行っています。
 さらに、がん細胞は特徴的なストレス応答をすることが知られています。そこで、がん細胞に特徴的な遺伝子発現の変化を解明することを通じ、がんを理解し、がんをコントロールする基礎研究にも取り組んでいます。

(2) イメージングを活用した生命現象の解明と応用

 病気や怪我をしたとき、レントゲン撮影やCT検査などの放射線を利用した診断が日常的に行われています。このように、生体内部の構造や機能の変化を鋭敏に捉える手法として放射線は非常に優れています。さらに、紫外線、可視光、赤外線などの様々な波長の光子も生命現象の可視化に多大な貢献をしています。まさに、「百聞は一見にしかず」といえます。我々の研究室では、イメージング解析にも力を入れており、細胞レベルから個体レベルのイメージング解析によって多様な生命現象の解明や医薬品開発に取り組んでいます。企業との共同研究にも力を入れ、新しいPET (positron emission tomography) 技術の開発にも取り組んでいます。

(3) 福島復興支援活動

 2011年に発生した東日本大震災ならびに東京電力福島第一原子力発電所事故では、福島県を中心に甚大な被害が起きました。私たちは、事故直後から福島県浜通りで放射能スクリーニング、被ばく調査、除染など様々な活動を行ってきました。事故から8年が経過しても、未だ原子力事故の傷跡が深く残っています。放射線に関する専門家として、私たちはこれからも福島復興支援の活動を行っていきます。

原著論文 ⟩⟩
  1. Imamura K., Takaya A., Ishida Y., Fukuoka Y., Taya T., Nakaki R., Kakeda M., Imamachi N., Sato A., Yamada T., Onoguchi-Mizutani R., Akizuki G., Tanu T.,Tao K., Miyao S., Suzuki Y., Nagahama M., Yamamoto T., Jensen TH. and Akimitsu N., Diminished nuclear RNA decay upon Salmonella infection upregulates antibacterial noncoding RNAs, EMBO J. 37, e97723
  2. Tano K., Onoguchi-Mizutani R., Yeasmin F., Uchiumi F., Suzuki Y., Yada T. and Akimitsu N. (2018) Identification of minimal p53 promoter region regulated by MALAT1 in human lung adenocarcinoma cells, Frontiers in Genetics. 8, 208
  3. Yamada T., Imamachi N., Mizutani R., Imamura K., Suzuki Y and Akimitsu N. (2017) 5'bromouridine IP Chase (BRIC)-seq to determine RNA half lives. Methods in Mol. Biol., 1720,1-13.
  4. Imamachi N., Salam K.A., Suzuki Y. and Akimitsu N. (2017) A GC-rich sequence feature in the 3’ UTR directs UPF1-dependent mRNA decay in mammalian cells. Genome Res. 27, 407-418.
  5. Okada T., Kurabayashi A., Akimitsu N. and Furihata M. (2017) Expression of cadherin-17 promotes metastasis in a highly bone marrow metastatic murine breast cancer model. BioMed Res. Inter., 2017, 8494286.
  6. Hermawan I., Furuta A., Higashi M., Fujita Y., Akimitsu N., Yamashita A., Moriishi K., Tsuneda S., Tani H., Nakakoshi M., Tsubuki M., Sekiguchi Y., Noda N. and Tanaka J. (2017) Four Aromatic Sulfates with an Inhibitory Effect against HCV NS3 Helicase from the Crinoid Alloeocomatella polycladia, Marine Drugs, 15,E117.
  7. Mizutani R., Imamachi N., Suzuki Y., Yoshida H., Tochigi N., Oonishi T., Suzuki Y., Akimitsu N. (2016) Oncofetal protein IGF2BP3 facilitates the activity of proto-oncogene protein eIF4E through the destabilization of EIF4E-BP2 mRNA. Oncogene, 35, 3495-3502
  8. Xia J., Inagaki Y., Sawakami T., Song P., Cai Y., Hasegawa K., Sakamoto Y., Akimitsu N. and Tang W. (2016) Preliminary investigation of five novel long non-coding RNAs in hepatocellular carcinoma cell lines. Biosci Trends., 10, 315-319.
  9. Katsura M., Cyou-Nakamine H., Zen Q., Zen Y., Nansai H., Amagasa S., Inoue T., Kaneki K., Taguchi A., Kobayashi M., Kaji T., Kodama T., Miyagawa K., Wada Y., Akimitsu N., and Sone H. (2016) Effects of Exposure to Low Dose Radiation on Differentiation in Human Neural Progenitor Cells. Sci. Rep., 6, 20027
  10. Maekawa S., Imamachi N., Irie T., Tani H., Matsumoto K., Mizutani R., Imamura K., Kakeda M., Yada T., Sugano S., Suzuki Y. and Akimitsu N. (2015) Analysis of RNA decay factor mediated RNA stability contributions on RNA abundance. BMC Genomics, 16, 154.
  11. Furuta A, Tsubuki M, Endoh M, Miyamoto T, Tanaka J, Salam KA, Akimitsu N, Tani H, Yamashita A, Moriishi K, Nakakoshi M, Sekiguchi Y, Tsuneda S, Noda N. (2015) Identification of Hydroxyanthraquinones as Novel Inhibitors of Hepatitis C Virus NS3 Helicase. Int J Mol Sci., 16, 18439-18453.
  12. Furuta A., Salam KA., Tani H., TsunedaS., Sekiguchi Y., Akimitsu N., and Noda N. (2015) A Fluorescence-Based Screening Assay for Identification of Hepatitis C Virus NS3 Helicase Inhibitors and Characterization of Their Inhibitory Mechanism, Methods in Mol. Biol., 1259, 211-228
  13. Tani H., Imamachi N., Mizutani R., Imamura K., Kwon Y., Miyazaki S., Maekawa S., Suzuki Y. and Akimitsu N. (2015) Genome-wide analysis of long noncoding RNA turnover, Methods in Mol. Biol., 1262, 305-320
  14. Salam KA., Furuta A., Noda N., Tsuneda S., Sekiguchi Y., Yamashita A., Moriishi K., Nakakoshi M., Tani H., Tanaka J., Tsubuki M., and Akimitsu N., (2014) PBDE: Structure-Activity Studies for the Inhibition of Hepatitis C Virus NS3 Helicase. Molecules, 19, 4006-4020
  15. Imamura K., Imamachi N., Akizuki G., Kumakura M., Kawaguchi A., Nagata K., Kato A., Kawaguchi Y., Sato H., Yoneda M., Kai C., Yada T., Suzuki Y., Yamada T., Ozawa T., Kaneki K., Inoue T., Kobayashi M., Kodama T., Wada Y., Sekimizu K. and Akimitsu N. (2014). Long noncoding RNA NEAT1-dependent SFPQ relocation between nuclear body paraspeckle and promoter mediates IL8 expression in response to immune stimuli. Mol. Cell, 53, 393-406
  16. Furuta A., Salam KA., Hermawan I., Akimitsu N., Tanaka J., Tani H., Yamashita A., Moriishi K., Nakakoshi M., Tsubuki M., Peng PW., Suzuki Y., Yamamoto N., Sekiguchi Y., Tsuneda S. and Noda N. (2014), Marine Drugs, 12, 462-76
  17. Imamachi N., Tani H., Mizutani R., Imamura K., Irie T., Suzuki Y. and Akimitsu N., (2014) BRIC-seq: a genome-wide approach for determining RNA stability in mammalian cells, Methods, 67, 55-63.
  18. Furuta A., Salam KA., Akimitsu N., Tanaka J., Tani H., Yamashita A., Moriishi K., Nakakoshi M., Tsubuki M., Sekiguchi Y., Tsuneda S. and Noda N. (2013) Cholesterol sulfate as a potential inhibitor of hepatitis C virus NS3 helicase., J. Enzyme Inhib. Med. Chem., 29, 223-229.
  19. Salam KA., Furuta A., Noda N., Tsuneda S., Sekiguchi Y., Yamashita A., Moriishi K., Nakakoshi M., Tsubuki M., Tani H., Tanaka J. and Akimitsu N., (2013) Psammaplin A inhibits hepatitis C virus NS3 helicase, J. Natur. Med., 64, 765-772.
  20. Tani H., Torimura M. and Akimitsu N., (2013) The RNA degradation pathway regulates the function of GAS5 a non-coding RNA in mammalian cells, PLoS ONE., 8, e55684.
  21. Tani H., Imamachi N., Salam KA., Mizutani R., Ijiri K., Irie T., Yada T., Suzuki Y., and Akimitsu N., (2013) Identification of hundreds of novel UPF1 target transcripts by direct determining whole transcriptome stability in mammalian cells, RNA Biology, 9,1370-1379.
  22. Fujimoto Y., Salam KA., Furuta A., Matsuda Y., Fujita O., Tani H., Ikeda M., Kato N., Sakamoto N., Maekawa S., Enomoto N., de Voogd NJ., Nakakoshi M., Tsubuki M., Sekiguchi Y., Tsuneda S., Akimitsu N., Noda N., Yamashita A., Tanaka J. and Moriishi K., (2012) Inhibition of both protease and helicase activities of hepatitis C virus NS3 by an ethyl acetate extract of marine sponge Amphimedon sp., PLoS ONE, 7, e48685
  23. Tani H., Mizutani R., Salam KA. Tano K., Ijiri K., Wakamatsu A., Isogai T., Suzuki Y. and Akimitsu N., (2012) Genome-wide determination of RNA stability reveals hundreds of short-lived non-coding transcripts in mammals, Genome Res., 22, 947-956.
  24. Miyagawa R., Tano K., Mizuno R., Nakamura Y., Ijiri K., Rakwal R., Shibato J., Masuo Y., Mayeda A., Hirose T. and Akimitsu N., (2012) Identification of cis- and trans-acting factors involved in the localization of MALAT-1 noncoding RNA to nuclear speckles., RNA., 18, 738-751.
  25. Mizutani R., Wakamatsu A., Tanaka N., Yoshida H., Tochigi N., Suzuki Y., Oonishi T., Tani H., Tano K., Ijiri K., Isogai T. and Akimitsu N., (2012) Identification and characterization of novel genotoxic stress-inducible nuclear long noncoding RNAs in mammalian cells., PLoS ONE, 7, e34949.
  26. Yamashita A., Salam KA., Furuta A., Matsuda Y., Fujita O., Tani H., Fujita Y., Fujimoto Y., Ikeda M., Kato N., Sakamoto N., Maekawa S., Enomoto N., Nakakoshi M., Tsubuki M., Sekiguchi Y., Tsuneda S., Akimitsu N., Noda N., Tanaka J., Moriishi K., (2012) Inhibition of hepatitis C virus replication and viral helicase by ethyl acetate extract of the marine feather star Alloeocomatella polycladia., Marine Drugs, 10, 744-761.
  27. Salam KA., Furuta A., Noda N., Tsuneda S., Sekiguchi Y., Yamashita A., Moriishi K., Nakakoshi M., Tsubuki M., Tani H., Tanaka J. and Akimitsu N. (2012) Inhibition of hepatitis C virus NS3 helicase by Manoalide., J. Nat. Prod., 75, 650-654.
  28. Tano K., Mizuno R., Okada T., Rakwal R., Shibato J., Masuo Y., Ijiri K. Akimitsu N. (2010) MALAT-1 enhances cell motility of lung adenocarcinoma cells by influencing the expression of motility-related genes., FEBS letters. 584, 4575-4580.
  29. Tani H., Nakamura Y., Ijiri K. and Akimitsu N. (2010) Stability of MALAT-1, a nuclear long non-coding RNA in mammalian cells, varies in various cancer cells., Drug Discov. Ther., 4, 235-239.
  30. Tano K., Hamamoto H., Ito T., Sumiya E., Rakwal R., Shibato J., Masuo Y., Ijiri K., Sekimizu K. and Akimitsu N. (2010) Reduced expression of Sytl 1 and Ccdc21 and impaired induction of Mt I by oxidative stress in SII-K1 knockout mice., Drug Discov. Ther., 4, 368-372.
  31. Tani H., Fujita O., Furuta A., Matsuda Y., Miyata R., Akimitsu N., Tanaka J., Tsuneda S., Sekiguchi Y. and Noda N., (2010) Real-time monitoring of RNA helicase activity using fluorescence resonance energy transfer in vitro., Biochem. Biophys. Res. Commun., 393, 131-136.
  32. Tani H., Akimitsu N., Fujita O., Matsuda Y., Miyata R., Tsuneda S., Igarashi M., Sekiguchi Y. and Noda N., (2009) High-throughput screening assay of hepatitis C virus helicase inhibitors using fluorescence-quenching phenomenon., Biochem. Biophys. Res. Commun., 379, 1054-1059.
  33. Takahashi M., Furihata M., Akimitsu N., Watanabe M., Kaul S., Yumoto N., and Okada T., (2008) A highly bone marrow metastatic murine breast cancer model established through in vivo selection exhibits enhanced anchorage-independent growth and cell migration mediated by ICAM-1., Clin. Exp. Metastasis, 25, 517-529.
  34. Takiguchi S., Yaguchi M., Ogawa K., Wada Y., Matsusue K., Ito T., Hamamoto H., Akimitsu N., Sekimizu K., Toh Y. and Iguchi H., (2008) Premature Aging-Like Phenotypes in Metastasis-Associated Protein I (Mta1) Null Mice, J. Bone Mineral Res. 23, S129.
  35. Akimitsu N., Tanaka J., and Pelletier J., (2007) Translation of nonSTOP mRNA is repressed post-initiation in mammalian cells., EMBO J., 26, 2327-2338.
  36. Takabatake N., Okamura M., Yokoyama N., Ikehara Y., Akimitsu N., Arimitsu N., Hamamoto H., Sekimizu K., Suzuki H., and Igarashi I., (2007) Glycophorin A-knockout mice, which lost sialoglycoproteins from the red blood cell membrane, are resistant to lethal infection of Babesia rodhaini., Vet. Parasitol., 148, 93-101.
  37. Ito T., Arimitsu N., Takeuchi M., Kawamura N., Nagata M., Saso K., Akimitsu N., Hamamoto H., Natori S., Miyajima A., and Sekimizu K., (2006) Transcription elongation factor S-II is required for definitive hematopoiesis., Mol. Cell. Biol., 26, 3194-3203.
  38. Aramaki Y., Ogawa K., Toh Y., Ito T., Akimitsu N., Hamamoto H., Sekimizu K., Matsusue K., Kono A., Iguchi H., and Takiguchi S., (2005) Direct interaction between metastasis-associated protein 1 and endophilin 3., FEBS Lett. 579, 3731-3736.
  39. Rungruang M., Kaneko O., Murakami Y., Tsuboi T., Hamamoto H., Akimitsu N., Sekimizu K., Kinoshita T., and Torii T., (2005) Erythrocyte surface glycosylphosphatidyl inositol anchored receptor for the malaria parasite., Mol. Biochem. Parasitol., 140, 13-21.
  40. Akimitsu N., Kim H-S., Hamamoto H., Kamura K., Fukuma N., Arimitsu N., Ono K., Wataya Y., Torii M. and Sekimizu K., (2004) Duffy antigen is important for lethality of the lethal strain P. yoelii 17XL., Parasitol. Res., 93,499-503.
  41. Ishida T.#, Akimitsu N.#, Kashioka T.#, Hatano M.#, Kubota T., Ogata Y., Sekimizu K., and Katayama T., (2004) DiaA, a novel DnaA-binding protein, ensures the timely initiation of Escherichia coli chromosome replication., J. Biol. Chem., 279, 45546-45555.
    #:equal contribution
  42. Hossain MS., Kurokawa K., Akimitsu N., and Sekimizu K., (2004) DNA topoisomerase II is required for the G0-to-S phase transition in Drosophila Schneider cells, but not in yeast. Genes Cells., 9, 905-917.
  43. Jilma B., Akimitsu N., Fukuma N., Sekimizu K., and Jilma-Stohlawetz P., (2004) Man, mouse and Duffy genotype-phenotype-specific pharmacokinetics of monocyte chemotactic protein-1., Transfus. Med., 14, 251-252.
  44. Akimitsu N., Kamura K., Tone S., Sakaguchi A., Kikuchi A., Hamamoto H. and Sekimizu K., (2003) Induction of apoptosis by depletion of DNA topoisomerase IIalpha in mammalian cells., Biochem. Biophys. Res. Commun., 307, 301-307.
  45. Kashiwazaki M., Tanaka T., Kanda H., Ebisuno Y., Izawa D., Fukuma N., Akimitsu N., Sekimizu K., Monden M. and Miyasaka M., (2003) A high endothelial venule-expressing promiscuous chemokine receptor DARC can bind inflammatory, but not lymphoid, chemokines and is dispensable for lymphocyte homing under physiological conditions., Int. Immunol., 15, 1219-1227.
  46. Arimitsu N., Akimitsu N., Kotani N., Takasaki S., Kina T., Hamamoto H., Kamura K. and Sekimizu K., (2003) Glycophorin A requirement for expression of O-linked antigens on the erythrocyte membrane., Genes Cells., 8, 769-777.
  47. Hossain MS., Akimitsu N., Kurokawa K. and Sekimizu K., (2003) Myogenic differentiation of Drosophila Schneider cells by DNA double-strand break-inducing drugs., Differentiation, 71, 271-280.
  48. Fukuma N., Akimitsu N., Hamamoto H., Kusuhara H., Sugiyama Y. and Sekimizu K., (2003) A role of the Duffy antigen for the maintenance of plasma chemokine concentrations., Biochem. Biophys. Res. Commun., 303, 137-139.
  49. Akimitsu N., Adachi N., Hirai H., Hossain MS., Hamamoto H., Kobayashi M., Aratani Y., Koyama H. and Sekimizu K., (2002) Enforced cytokinesis without complete nuclear division in embryonic cells depleting the activity of DNA topoisomerase IIalpha., Genes Cells., 8, 393-402.
  50. Kaito C., Akimitsu N., Watanabe H. and Sekimizu K., (2002) Silkworm larvae as an animal model of bacterial infection pathogenic to humans., Microb. Pathog., 32, 183-190.
  51. Koyanagi-Katsuta R., Akimitsu N., Hamamoto H., Arimitsu N., Hatano T. and Sekimizu K., (2002) Embryonic lethality of mutant mice deficient in the p116 gene., J. Biochem., 131, 833-837.
  52. Kaito C., Kurokawa K., Hossain MS., Akimitsu N. and Sekimizu K., (2002) Isolation and characterization of temperature-sensitive mutants of the Staphylococcus aureus dnaC gene., FEMS Microbiol. Lett., 210, 157-164.
  53. Hossain MS., Akimitsu N., Takaki T., Hirai H. and Sekimizu K., (2002) ICRF-193, a catalytic inhibitor of DNA topoisomerase II, inhibits re-entry into the cell division cycle from quiescent state in mammalian cells., Genes Cells, 7, 285-295.
  54. Inoue R., Kaito C., Tanabe M., Kamura K., Akimitsu N. and Sekimizu K., (2001) Genetic identification of two distinct DNA polymerases, DnaE and PolC, that are essential for chromosomal DNA replication in Staphylococcus aureus., Mol. Genet. Genomics, 266, 564-571.
  55. Koyanagi-Katsuta R., Akimitsu N., Arimitsu N., Hatano T., and Sekimizu K., (2000) Apoptosis of mouse embryonic stem cells induced by single cell suspension., Tissue Cell, 32, 66-70.
  56. Akimitsu N., Hamamoto H., Inoue R., Shoji M., Akamine A., Takemori K., Hamasaki N., and Sekimizu K., (1999) Increase in resistance of methicillin-resistant Staphylococcus aureus to beta-lactams caused by mutations conferring resistance to benzalkonium chloride, a disinfectant widely used in hospitals., Antimicrob. Agents Chemother., 43, 3042-3043.
  57. Ohba A., Inoue R., Akimitsu N., Mizushima T., and Sekimizu K., (1998) Identification of proteins whose amounts are altered by mutation in the pgsA gene of Escherichia coli., Biol. Pharm. Bull., 21, 1139-1141.
  58. Katayama T. #, Akimitsu N. #, Mizushima T., Miki T., and Sekimizu K., (1997) Overinitiation of chromosome replication in the Escherichia coli dnaAcos mutant depends on activation of oriC function by the dam gene product., Mol. Microbiol., 25, 661-670.
    #:equal contribution
  59. Katayama T., Kubota T., Takata M., Akimitsu N., and Sekimizu K., (1996) Disruption of the hslU gene, which encodes an ATPase subunit of the eukaryotic 26S proteasome homolog in Escherichia coli, suppresses the temperature-sensitive dnaA46 mutation., Biochem. Biophys. Res. Commun., 229, 219-224.
  60. Akimitsu N., Mizushima T., Suzuki E., Miki T., Sekimizu K., (1996) Growth phenotypes of Escherichia coli carrying a mutation of acidic phospholipid synthesis., Biol. Pharm. Bull., 19, 1275-1278.
英文総説 ⟩⟩
  1. Yamada T., Nagahama M. and Akimitsu N. (2017) Interplay Between Transcription and RNA degradation. in Gene Expression and Regulation in Mammalian Cells: InTechOpen, in press
  2. Mizutani R., Yamada T. and Akimitsu N. Techniques for genome-wide expression analysis of non-coding RNA. in Handbook of Epigenetics, 2nd Edition: The New Molecular and Medical Genetics (ISBN: 978-0-12-805388-1). (2017)
  3. Imamura K. and Akimitsu N. (2014) Long non-coding RNAs involved in immune responses, Front. Immunol., 5, 573.
  4. Salam KA. and Akimitsu N., (2013) Hepatitis C Virus NS3 Inhibitors: Current and Future Perspectives, BioMed. Res. Inter., Article ID 467869
  5. Tani T. and Akimitsu N., (2012) Genome-wide technology for determination of RNA stability in mammalian cells: Historical perspective and recent advantages based on modified nucleotide labeling, RNA Biology, 9, 1233-1238.
  6. Tano K. and Akimitsu N., (2012) Long Non-coding RNAs In Cancer Progression, Front. Genet., 3, 1-6.
  7. Imamachi N., Tani H. and Akimitsu N., Up-frameshift protein 1 (UPF1): Multitalented entertainer in RNA decay., (2012) Drug Discov. Ther., 6, 55-61.
  8. Tano K., Nagata M. and Akimitsu N., S-II mediated gene regulation., (2008) Drug Discov. Ther., 2, 136-139.
  9. Akimitsu N., (2008) Messenger RNA surveillance systems monitoring proper translation termination., J. Biochem., 143, 1-8.
  10. Hamamoto H., Akimitsu N., Arimitsu N. and Sekimizu K., (2008) Role of the Duffy antigen and glycophorin A in malaria infection and erythrocyte. Drug Discov. Ther., 2, 58-63.
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