Our organization, departments, staff and researchers
Takamitsu Unoki
The research group I work for : Pathomechanism Group
With a focus placed on factors that control the redox (reduction-oxidation) balance in a living organism, such as molecules of hypervalent sulfur, I am working to solve molecule-level mechanisms involving methylmercury toxicity and defense against it and to find their applications (as a biomarker, etc.).
Research theme - Areas of work
Basic Research
FY2020-2024 Research on the methylmercury-induced alteration of protein function and its protective factors (Principal Investigator)
FY2018-2019 Research on selective cytotoxicity of methylmercury focusing on sulfur nucleophiles (Principal Investigator)
Project research
FY2020-2024 Basic research on neurotoxicity mechanisms in methylmercury poisoning and on the prevention and treatment to address them (Collaborator)
Main research achievements
Original articles
2022
Akiyama, M., Unoki, T., Aoki, H., Nishimura, A., Shinkai, Y., Warabi, E., Nishiyama, K., Furumoto, Y., Anzai, N., Akaike, T., Nishida, M., Kumagai, Y. (2022). Cystine-dependent antiporters buffer against excess intracellular reactive sulfur species-induced stress. Redox Biol. in press. DOI: 10.1016/j.redox.2022.102506
Fujimura, M., Unoki, T. (2022). Preliminary evaluation of the mechanism underlying vulnerability/resistance to methylmercury toxicity by comparative gene expression profiling of rat primary cultured cerebrocortical and hippocampal neurons. J. Toxicol. Sci. 47, 211-219. DOI: 10.2131/jts.47.211
Horai, S., Abiko, Y., Unoki, T., Shinkai, Y., Akiyama, M., Nakata, K., Kunisue, T., Kumagai, Y. (2022). Concentrations of nucleophilic sulfur species in small Indian mongoose (Herpestes auropunctatus) in Okinawa, Japan. Chemosphere 133833. DOI: 10.1016/j.chemosphere.2022.133833
Unoki, T., Akiyama, M., Shinkai, Y., Kumagai, Y., Fujimura, M. (2022). Spatio-temporal distribution of reactive sulfur species during methylmercury exposure in the rat brain. J. Toxicol. Sci. 47, 31-37. DOI: 10.2131/jts.47.31Paper presented.
2020
Fujimura, M., Usuki, F., Unoki, T. (2020). Decreased plasma thiol antioxidant capacity precedes neurological signs in a rat methylmercury intoxication model. Food Chem. Toxicol. 146, 111810. DOI: 10.1016/j.fct.2020.111810Paper presented.
Akiyama, M., Unoki, T., Yoshida, E., Ding,Y., Yamakawa, H., Shinkai, Y., Ishii, I., Kumagai, Y. (2020). Repression of mercury accumulation and adverse effects of methylmercury exposure is mediated by cystathionine γ-lyase to produce reactive sulfur species in mouse brain. Toxicol. Lett. 330, 128-133. DOI: 10.1016/j.toxlet.2020.05.007
Akiyama, M., Unoki, T., Kumagai,Y. (2020). Combined exposure to environmental electrophiles enhances cytotoxicity and consumption of persulfide. Fundam. Toxicol. Sci. 7, 161-166. DOI: 10.2131/fts.7.161
2019
Akiyama, M., Unoki, T., Shinkai, Y., Ishii, I., Ida, T., Akaike, T., Yamamoto, M., Kumagai, Y. (2019). Environmental electrophile-mediated toxicity in mice lacking Nrf2, CSE, or both. Environ. Health Perspect. 127, 67002. DOI: 10.1289/EHP4949Paper presented.
2017
Akiyama, M., Shinkai, Y., Unoki, T., Shim, I., Ishii, I., and Kumagai, Y. (2017). The Capture of Cadmium by Reactive Polysulfides Attenuates Cadmium-Induced Adaptive Responses and Hepatotoxicity. Chem. Res. Toxicol. 30, 2209-2217. DOI: 10.1021/acs.chemrestox.7b00278
Abiko, Y., Shinkai, Y., Unoki, T., Hirose, R., Uehara, T., and Kumagai, Y. (2017). Polysulfide Na2S4 regulates the activation of PTEN/Akt/CREB signaling and cytotoxicity mediated by 1,4-naphthoquinone through formation of sulfur adducts. Sci. Rep. 7, 4814. DOI: 10.1038/s41598-017-04590-z
Abiko, Y., Sha, L., Shinkai, Y., Unoki, T., Luong, N.C., Tsuchiya, Y., Watanabe, Y., Hirose, R., Akaike, T., and Kumagai, Y. (2017). 1,4-Naphthoquinone activates the HSP90/HSF1 pathway through the S-arylation of HSP90 in A431 cells: Negative regulation of the redox signal transduction pathway by persulfides/polysulfides. Free Radic. Biol. Med. 104, 118-128. DOI: 10.1016/j.freeradbiomed.2016.12.047
2016
Unoki, T., Abiko, Y., Toyama, T., Uehara, T., Tsuboi, K., Nishida, M., Kaji, T., and Kumagai, Y. (2016). Methylmercury, an environmental electrophile capable of activation and disruption of the Akt/CREB/Bcl-2 signal transduction pathway in SH-SY5Y cells. Sci. Rep. 6, 28944. DOI: 10.1038/srep28944
2012
Hasegawa, H., Noguchi, J., Yamashita, M., Okada, R., Sugimoto, R., Furuya, M., Unoki, T., Funakoshi, Y., Baba, T., and Kanaho, Y. (2012). Phosphatidylinositol 4-phosphate 5-kinase is indispensable for mouse spermatogenesis. Biol. Reprod. 86, 136, 131-112. DOI: 10.1095/biolreprod.110.089896
Unoki, T., Matsuda, S., Kakegawa, W., Van, N.T., Kohda, K., Suzuki, A., Funakoshi, Y., Hasegawa, H., Yuzaki, M., and Kanaho, Y. (2012). NMDA receptor-mediated PIP5K activation to produce PI(4,5)P2 is essential for AMPA receptor endocytosis during LTD. Neuron 73, 135-148. DOI: 10.1016/j.neuron.2011.09.034F1000Prime Recommended
2007
Nakano-Kobayashi, A., Yamazaki, M., Unoki, T., Hongu, T., Murata, C., Taguchi, R., Katada, T., Frohman, M.A., Yokozeki, T., and Kanaho, Y. (2007). Role of activation of PIP5Kγ661 by AP-2 complex in synaptic vesicle endocytosis. EMBO J. 26, 1105-1116. DOI: 10.1038/sj.emboj.7601573
Reviews
2020
Unoki, T., Akiyama, M., Kumagai, Y. (2020). Nrf2 Activation and Its Coordination with the Protective Defense Systems in Response to Electrophilic Stress. Int. J. Mol. Sci. 21, 545. DOI: 10.3390/ijms21020545Paper presented.
2019
Kumagai, Y., Akiyama, M., Unoki, T. (2019). Adaptive Responses to Electrophilic Stress and Reactive Sulfur Species as their Regulator Molecules. Toxicol. Res. 35, 303-310. DOI: 10.5487/TR.2019.35.4.303
2018
Unoki, T., Akiyama, M., Kumagai, Y., Gonçalves, F.M., Farina, M., da Rocha, J.B.T., Aschner, M. (2018). Molecular pathways associated with methylmercury-induced Nrf2 modulation. Front. Genet. 9, 373. DOI: 10.3389/fgene.2018.00373
2012
Kanaho, Y., and Unoki, T. (2012). Regulation and functions of the lipid kinase PIP5Kγ661 at synapses. Adv. Enzyme Regul. 52, 59-65.
Other
2019
Unoki T (2019). Topics: Highly efficient removal of mercury out of water using platinum film electrode. Pharmacia, 55, 704 DOI: 10.14894/faruawpsj55.7_704
Externally-funded research
FY2022-2024 JSPS Grant-in-Aid for Scientific Research (B) (Co-Investigator)
Development of biomarkers that can objectively determine differences in individual susceptibility to methylmercury poisoning
FY2021-2023 JSPS Grant-in-Aid for Scientific Research (C) (Principal Investigator)
Study on selective cytotoxicity of methylmercury focusing on active sulfur moleculeE
FY2019-2022 JSPS Grant-in-Aid for Early-Career Scientists (Principal Investigator)
Research on selective cellular damage from methylmercury, focusing on active sulfurous molecules
FY2016-2017 JSPS Grant-in-Aid for Early-Career Scientists (B) (Principal Investigator)
Research on detoxification mechanism of environmental electrophiles mediated by reactive sulfur species
Main career history, academic history, academic degrees, awards, etc.
2018Senior Researcher, Department of Basic Medical Sciences, National Institute for Minamata Disease
2014Assistant Professor, Faculty of Medicine, University of Tsukuba
2012Research Fellow, Faculty of Medicine, University of Tsukuba
2012Ph.D. in Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, completed (Ph. D. (Medicine))
