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Uchiumi Takeshi Last modified date：2024.06.03

Professor / Department of Health Sciences,
Department of Health Sciences
Faculty of Medical Sciences


Graduate School
Department of Health Sciences
Graduate School of Medical Sciences
Undergraduate School
Biological Sciences and Technology
School of Medicine


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Homepage
https://kyushu-u.elsevierpure.com/en/persons/takeshi-uchiumi
　Reseacher Profiling Tool　Kyushu University Pure
Phone
092-642-6712
Fax
092-642-6712
Academic Degree
Medical Doctor　, Doctor of Philosophy
Country of degree conferring institution (Overseas)
No
Field of Specialization
Biochemistry, Molecular Biology、Clinical chemistry、Clinical Chemistry and Laboratory Medicine
Total Priod of education and research career in the foreign country
02years00months
Outline Activities
The Department of Health Science Laboratory Technology is working to develop the infrastructure of clinical chemistry and new measurement methods. In addition, mitochondrial research is being conducted as basic research. Mitochondrial DNA encodes the electron-transfer subunit that synthesizes ATP and is essential for cells to exist and function normally. Mitochondria are the largest site of reactive oxygen species generation in the cell, and mitochondrial DNA there is subject to very strong oxidative damage, and the concept that mitochondrial DNA mutations play an important role in the development and metastasis of diseases such as cancer, as well as in individual aging, is accepted. Functional analysis of genes involved in mitochondrial DNA replication, transcription, and translation is underway. Specifically, we are focusing on the mitochondrial ribosome-binding ERAL1 gene, which regulates translation, and the RNA-binding LRP130 gene. Functional analysis includes measurement of mitochondrial function (membrane potential, generation of reactive oxygen species, cell survival, and cell cycle) when gene expression is decreased by siRNA introduction, and functional evaluation (2) The CSD (cold shock domain) family of proteins has a nucleic acid binding domain consisting of approximately 78 amino acids that is highly conserved from E. coli to humans. CSD family proteins are ubiquitous proteins with a nucleic acid-binding domain consisting of about 78 amino acids that are highly conserved from E. coli to humans, and are expressed in many proliferating cells. In this study, (1) YB-1 knockout mice were generated and their functions were elucidated. Homozygous YB-1 knockout mice were embryonic lethal. (2) YB-1 was expressed almost throughout the mouse fetus by in situ hybridization. (3) YB-1 binds to the outer mitochondrial membrane and is involved in translation. (4) When YB-1 knockout fibroblasts were generated, cell proliferation was also decreased in experiments using YB-1 siRNA, confirming that the expression of EF-1 was upregulated upon YB-1 siRNA transfection. This suggests that YB-1 is deeply involved in cell proliferation, suggesting that YB-1 affects the expression of various proteins at the translational level. Furthermore, (5) YB1 was found to harbor a variety of microRNAs. This suggests that YB1 may be a potential molecular target in cancer, which could serve as a basis for new drug design. (6) Functional analysis of the mitochondrial matrix protein p32: From the individual level to the molecular level, we will examine how the mitochondria of intracellular organelles affect cells and individuals (7) Elucidation of new molecular mechanisms inferred from analysis of tissue-specific knockout mice of p32
Research
Research Interests
  • Physiological function analysis of mitochondrial protein ABCB10
    keyword : mitochondria transporter
    2022.06～2025.06.
  • New molecular mechnism of the functional interaction between mitochondria and lysosome
    keyword : mitochondria, lysosome, NAD, functional interaction
    2020.06～2026.06.
  • New approch for measurement of clinical chemistry

    keyword : Clinical chemistry
    2019.05～2022.05.
  • Mitochondria and cancer
    keyword : mitochondria
    2016.05～2016.05.
  • Functional analysis of mitochondrial protein p32
    keyword : p32 , mitochondria , translation
    2010.05～2018.05.
  • Cross talk between cytoplasm and mitochndria translation
    keyword : mitochondria translation
    2008.05～2012.05.
  • Mitochondria related gene and Cancer
    keyword : Mitochondria , tumor, translation, replication, siRNA
    2007.06～2010.05.
  • Multifunction of YB-1 gene response to stress- cross-talk to translation, transcription and repair
    keyword : YB-1, translation, transcription, repair
    1998.04～2008.03.
Academic Activities
Books
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Reports
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Papers
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1. K. Igami, H. Kittaka, M. Yagi, K. Gotoh, Y. Matsushima, T. Ide, M. Ikeda, S. Ueda, S. Nitta, M. Hayakawa, KI. Nakayama, M. Matsumoto, D. Kang, and T. Uchiumi, iMPAQT reveals that adequate mitohormesis from TFAM overexpression leads to life extension in mice, Life Science Alliance, 2024.07.
2. Y. Do, M. Yagi, H. Hirai, K, Miki, Y.Fukahori, D. Setoyama, M. Yamamoto, T. Furukawa, Y. Kunishaki, D. Kang, and T. Uchiumi, Cardiomyocyte-specific deletion of the mitochondrial transporter ABCB10 causes cardiac dysfunction via lysosomal-mediated ferroptosis, BioScience Reports, 2024.05.
3. T. Toshima, M. Yagi, Y. Do, H. Hirai, Y. Kunisaki, D. Kang T. Uchiumi, Mitochondrial translation failure represses cholesterol gene expression via Pyk2-Gsk3β-Srebp2 axis, Life Science Alliance, 2024.04.
4. K. Miki, M.Yagi, D. Kang, Y. Kunisaki, K. Yoshimoto and T. Uchiumi, Glucose starvation causes ferroptosis-mediated lysosomal dysfunction, iScience, 2024.04.
5. S. Ueda, M. Yagi, E. Tomoda, S. Matsumoto, Y. Ueyanagi, Y. Do, D. Setoyama, Y. Matsushima, A. Nagao, T. Suzuki, Y.Mori, N.Oyama, D. Kang, and T. Uchiumi, Mitochondrial haplotype mutation alleviates respiratory defect of melas by restoring taurine modification in tRNA with 3243A > G mutation, Nucleic Acids Res, 2023.07.
6. M. Yagi, Y. Do, H. Hirai, K. Miki, T. Toshima, Y. Fukahori, D. Setoyama, C. Abe, YI. Nabeshima , D. Kang, and T. Uchiumi, Improving lysosomal ferroptosis with NMN administration protects against heart failure, Life Sci Alliance, 2023.06.
7. K. Miki, M.Yagi, N. Noguchi, Y. Do, R. Otuji, D. Kuga, D. Kang, Y. Yoshimoto and T. Uchiumi*, Induction of glioblastoma cell ferroptosis using combined treatment with chloramphenicol and 2-deoxy-D-glucose, Sci Rep , 2023.06.
8. Yagi, M., Toshima, T., Amamoto, R., Do, Y., Hirai, H., Setoyama, D., Kang, D. & Uchiumi, T.,, Mitochondrial translation deficiency impairs NAD+-mediated lysosomal acidification, EMBO Journal, 40, 8, e105268., 2021.04.
9. 内海 健, Mutation and functional analysis of ABCC2/multidrug resistance protein 2 in a Japanese patient with Dubin-Johnson syndrome., Hepatol. Research, 43, 569-575, 2013.02.
10. Fukuda, T., Ashizuka, M., Nakamura, T., Shibahara,K., Maeda, K., Izumi, I., Kohno, K., Kuwano, M.,and Uchiumi,T.,, Characterization of 5'untranslated region of YB-1 mRNA and plausible regulation of translation., Nucleic Acid Res, 2004.01.
11. Kuwano, M., Uchiumi, T., Hayakawa, H., Ono, M., Wada, M., Izumi, H., and Kohno, K, The basic and clinical implications of ABC transporters, Y-box-binding protein-1 (YB-1) and angiogenesis-related factors in human malignancies., Cancer Sci, 10.1111/j.1349-7006.2003.tb01344.x, 94, 1, 9-14, 94: 9-14, 2003.01.
12. Kohno K, Izumi H, Uchiumi T, Ashizuka M, and Kuwano M, The pleiotropic functions of the Y-box-binding protein, YB-1, Bioessays, 10.1002/bies.10300, 25, 7, 691-698, 25: 691-698, 2003.01.
13. Ashizuka, M., Fukuda, T., Nakamura, T., Shirasuna, K., Iwai, K., Izumi, H., Kohno, K., Kuwano, M., and Uchiumi, T., Novel translational control through an iron-responsive element by interaction of multifunctional protein YB-1 and IRP2., Mol Cell Biol, 10.1128/MCB.22.18.6375-6383.2002, 22, 18, 6375-6383, 22: 6375-6383, 2002.01.
14. Hashimoto K.,Uchiumi T., Konno T., Ebihara T., Nakamura T., Wada M., Sakisaka S., Maniwa F., Amachi T., Ueda K., and Kuwano M., Trafficking and functional defects by mutations of the ATP-binding domains in MRP2 in patients with Dubin-Johnson syndrome., Hepatology, 10.1053/jhep.2002.36368, 36, 5, 1236-1245, 36:1236-1245, 2002.01.
15. Haga, S., Hinoshita, E., Ikezaki, K., Fukui, M., Scheffer, G. L., Uchiumi, T. and Kuwano, M., Involvement of the multidrug resistance protein 3 in drug sensitivity and its expression in human glioma., Jpn. J. Cancer Res, 92, 2, 211-219, 92: 211-219, 2001.01.
16. Hinoshita, E., Taguchi, K., Inokuchi, A., Uchiumi, T., Kinukawa, N., Shimada, M., Tsuneyoshi, M., Sugimachi, K. and Kuwano, M., Decreased expression of an ATP-binding cassette transporter, MRP2, in human livers with hepatitis C virus infection., J. Hepatology, 10.1016/S0168-8278(01)00216-1, 35, 6, 765-773, 35,765-773, 2001.01.
17. Inokuchi, A., Hinoshita, E., Wada, M., Iwamoto, Y., Kohno, K., Kuwano, M. and Uchiumi, T., Enhanced expression of Human Multidrug resistance protein 3 by bile salt in human enterocytes: a transcriptional control of plausible bile acid transporter., J. Biol. Chem., 10.1074/jbc.M104612200, 276, 50, 46822-46829, 276: 46822-46829, 2001.01.
18. Hinoshita, E., Uchiumi, T., Taguchi, K., Kinukawa, N., Tsuneyoshi, M., Maehara, Y., Sugimachi, K. and Kuwano, M., Increased expression of an ATP-binding cassette superfamily transporter, multidrug resistance protein 2, in human colorectal carcinomas., Clin Cancer Res, 6, 6, 2401-2407, 6:2401-2407, 2000.01.
19. Kawabe, T., Chen, Z., Wada, M., Uchiumi, T., Ono, M., Akiyama, S. and Kuwano, M., Enhanced transport of anticancer agents and leukotriene C4 by the human canalicular multispecific organic anion transporter (cMOAT/MRP2)., FEBS Lett., 10.1016/S0014-5793(99)00979-5, 456, 2, 327-331, 456: 327-331, 1999.01.
20. Tanaka,T., Uchiumi,T., Hinoshita,E., Inokuchi,A., Toh,S., Wada,M., Takano,H., Kohno,K., and Kuwano,M., The human multispecific resistance protein2 gene : functional characterization of 5'-flanking region and expression in hepatic cells., Hepatology, 30: 1507-1512, 1999.01.
21. Uchiumi, T., Longo, D. and Ferris, D, Cell cycle regulation of PLK promoter., J. Bio. Chem, 272,9166-9174, 1997.01.
22. Uchiumi, T., Hinoshita, E., Haga, S., Nakamura, T., Tanaka, T., Toh, S., Furukawa, M., Kawabe, T., Wada, M., Kagotani, K., Okumura, K., Kohno, K., Akiyama, S. and Kuwano, M., Isolation of a novel human canalicular multispecific organic anion transporter, cMOAT2/MRP3, and its expression in cisplatin-resistant cancer cells with decreased ATP-dependent drug transport., Biochem. Biophys. Res. Commun, 10.1006/bbrc.1998.9546, 252, 1, 103-110, 252: 103-110, 1998.01.
Presentations
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1. 内海 健, KANG DONGCHON, 八木美佳子, Cardiomyocyte Specific Deletion of p32/C1qbp Causes Mitochondrial Cardiomyopathy, EuroMit, 2014.06.
2. 内海 健, p32/gC1qR is indispensable for fetal development and mitochondrial translation: importance of its RNA binding ability, ミトコンドリア学会, 2013.11.
Membership in Academic Society
  • American Association of Cancer Research
  • Japanease Cancer Association
Educational
Educational Activities
I teach first, second, and third year health science courses as part of my undergraduate education.
Clinical Chemistry I, Clinical Chemistry II, and Introduction to Laboratory Management,
The fourth-year undergraduate students are instructed in basic research as their graduation research.
As for graduate education, 2 students in the doctoral course of the School of Medicine, 1 student in the doctoral course of the School of Health Sciences, and 6 students in the master's course are engaged in research activities.


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