Kyushu University Academic Staff Educational and Research Activities Database
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matsunaga naoya Last modified date:2023.11.14

Professor / Department of Clincal Pharmacokinetics, Faculty of Pharmaceutical Sciences, Kyushu University
Department of Pharmaceutical Health Care and Sciences
Faculty of Pharmaceutical Sciences

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Academic Degree
Country of degree conferring institution (Overseas)
Field of Specialization
Chronopharmacology, Chronopharmaceutics(chrono-DDS),Chrono drug discovery, Microcurrent therapy of molecular clock
Total Priod of education and research career in the foreign country
Research Interests
  • Research on LNP(Lipid NanoParticle)
    keyword : LNP(Lipid NanoParticle)
  • Research on cognitive dysfunction.
    keyword : cognitive dysfunction
  • Microcurrent therapy of circadina clock
    keyword : Microcurrent therapy circadina clock
  • Drug discovery of anti-cancer and anti-inflammatory based on circadian machinery
    keyword : chrono-drug discovery
  • Study on proper use for medicine of which it is basic is biological rhythm

    New DDS development of which it is basic is biological rhythm
    keyword : chronopharmacology  chronotherapy
Academic Activities
1. Ohdo S, Koyanagi S, Matsunaga N. , Chronopharmacological strategies: Intra- and inter-individual variability of molecular clock. , Adv Drug Deliv Rev., 2010.08.
2. Ohdo S, Koyanagi S, Matsunaga N, Hamdan A., Molecular basis of chronopharmaceutics., J Pharm Sci., 2011.09.
1. Fukuoka K, Yoshida Y, Sotono K, Nishikawa N, Hamamura K, Oyama K, Tsuruta A, Mayanagi K, Koyanagi S, Matsunaga N, Ohdo S., Oral administration of vancomycin alleviates heart failure triggered by chronic kidney disease.
, Biochem Biophys Res Commun. , 675, 92-98., 2023.10.
2. Taniguchi M, Yasukochi S, Yamakawa W, Tsurudome Y, Tsuruta A, Horiguchi M, Ushijima K, Yamashita T, Shindo N, Ojida A, Matsunaga N, Koyanagi S, Ohdo S., Inhibition of Tumor-Derived C-C Motif Chemokine Ligand 2 Expression Attenuates Tactile Allodynia in NCTC 2472 Fibrosarcoma-Inoculated Mice., Mol Pharmacol., 104, 2, 73-79. , 2023.08.
3. Yamane D, Tetsukawa R, Zenmyo N, Tabata K, Yoshida Y, Matsunaga N, Shindo N, Ojida A., Expanding the Chemistry of Dihaloacetamides as Tunable Electrophiles for Reversible Covalent Targeting of Cysteines., J Med Chem., 66, 13, 9130-9146, 2023.07.
4. Tsuruta A, Kanetani D, Shiiba Y, Inoki T, Yoshida Y, Matsunaga N, Koyanagi S, Ohdo S., Modulation of cell physiology by bispecific nanobodies enabling changes in the intracellular localization of organelle proteins., Biochem Pharmacol. , 2023.09.
5. Tsuruta A, Shiiba Y, Matsunaga N, Fujimoto M, Yoshida Y, Koyanagi S, Ohdo S., Diurnal expression of PD-1 on tumor-associated macrophages underlies the dosing time-dependent anti-tumor effects of the PD-1/PD-L1 inhibitor BMS-1 in B16/BL6 melanoma-bearing mice., Mol Cancer Res, MCR-21-0786-E.2021., 2022.04.
6. Matsunaga N, Yoshida Y, Kitajou N, Shiraishi A, Kusunose N, Koyanagi S, Ohdo S, Microcurrent stimulation activates the circadian machinery in mice., Biochem Biophys Res Commun., 10.1016/j.bbrc.2019.02.022., (19), 30203-30207, 2019.03, The circadian rhythm, which regulates various body functions, is transcriptionally controlled by a series of clock gene clusters. The clock genes are related to the pathology of various kinds of diseases, which in turn, is related to aging. Aging in humans is a worldwide problem; it induces sleep disorders and disruption of the circadian rhythm. It also decreases ocular vision and appetite and weakens the synchronization of clock genes by light and food. Therefore, a simple method for the synchronization of clock genes in the body is required. In this study, the influence of microcurrent stimulation (MCS) on the circadian machinery in wild-type (WT) and Clock mutant (Clk/Clk) mice was investigated. MCS induced Per1 mRNA expression in cultured mouse astrocytes; cAMP response element (CRE) in the Per1 mouse promoter was found to be important for the induction of Per1 mRNA. In addition, MCS increased the Per1 mRNA levels in mouse livers and caused the phase advance of the Per1 expression rhythm. The protein expression rhythm of phosphor-cAMP response element-binding protein (pCREB) was altered and the phase of expression of pCREB protein advanced. Finally, the influence of MCS on the locomotor activity rhythm in WT and Clk/Clk mice was investigated. MCS caused the phase advance of the locomotor activity rhythm in WT and Clk/Clk mice. The results of this study indicate that MCS activated the clock machinery in mice; MCS may thus improve the quality of new treatment modalities in the future..
7. Matsunaga Naoya, Takashi Ogino, Yukinori Hara, Takahiro Tanaka, Koyanagi Satoru, Shigehiro Ohdo, Optimized dosing schedule based on circadian dynamics of mouse breast cancer stem cells improves the antitumor effects of aldehyde dehydrogenase inhibitor, Cancer Research, 10.1158/0008-5472.CAN-17-4034, 78, 13, 3698-3708, 2018.07, Although malignant phenotypes of triple-negative breast cancer (TNBC) are subject to circadian alterations, the role of cancer stem cells (CSC) in defining this circadian change remains unclear. CSC are often characterized by high aldehyde dehydrogenase (ALDH) activity, which is associated with the malignancy of cancer cells and is used for identification and isolation of CSC. Here, we show that the population of ALDH-positive cells in a mouse 4T1 breast tumor model exhibits pronounced circadian alterations. Alterations in the number of ALDHpositive cells were generated by time-dependent increases and decreases in the expression of Aldh3a1. Importantly, circadian clock genes were rhythmically expressed in ALDH-negative cells, but not in ALDH-positive cells. Circadian expression of Aldh3a1 in ALDH-positive cells was dependent on the timedependent release of Wingless-type mmtv integration site family 10a (WNT10a) from ALDH-negative cells. Furthermore, antitumor and antimetastatic effects of ALDH inhibitor N,N-diethylaminobenzaldehyde were enhanced by administration at the time of day when ALDH activity was increased in 4T1 tumor cells. Our findings reveal a new role for the circadian clock within the tumor microenvironment in regulating the circadian dynamics of CSC. These results should enable the development of novel therapeutic strategies for treatment of TNBC with ALDH inhibitors. Significance: This seminal report reveals that circadian dynamics of CSC are regulated by the tumor microenvironment and provides a proof of principle of its implication for chronotherapy in TNBC..
Other Educational Activities
  • 2019.04.
  • 2018.04.
  • 2017.04.
  • 2016.10.
  • 2015.12.
  • 2014.12.
  • 2013.12.
  • 2012.12.
  • 2011.12.
  • 2010.12.
  • 2009.12.
  • 2008.12.