Faculty Profiles - TSURUTA AKITO

Information

写真a

TSURUTA AKITO

Organization

Faculty of Pharmaceutical Sciences Department of Pharmaceutical Health Care and Sciences Assistant Professor

Contact information

Tel

0926426612

Profile

概日時計機構を基盤とした、炎症病態およびがん増殖メカニズムの解析を行っている。

External link

Research Areas

Life Science / Tumor biology

Degree

Pharmacy, Ph.D

Research Interests・Research Keywords

Research theme：Mechanism of glioma malignant transformation mediated by RNA acetylation

Keyword：Acetylation of RNA, Glioma

Research period： 2021.5 - 2024.5
Research theme：Analysis of the mechanism of tumor progression based on circadian clock in tumor microenvironment

Keyword：tumor microenvironment, circadian clock

Research period： 2021.4 - 2025.3
Research theme：the analysis of mechanism for acquisition of tumor malignant phenotype based on molecular circadian clock.

Keyword：tumor, circadian clock

Research period： 2019.4 - 2020.9

Awards

ふくおか公衆衛生推進機構　研究奨励賞

2023.12
奨励賞

2023.12 ふくおか公衆衛生推進機構

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九州がんプロ養成プラン研究奨励賞

2021.2 新ニーズに対応する九州がんプロ養成プラン事業運営推進協議会
中村治四郎奨励金

2020.11 中村治四郎育英会
APSTJ Global Education Seminar presentation award

2016.10

Papers

RNA editing enzyme ADAR2 regulates P-glycoprotein expression in murine breast cancer cells through the circRNA-miRNA pathway

Omata, Y; Haraguchi, M; Yoshinaga, S; Ogino, T; Okawa, M; Tsuruta, A; Koyanagi, S; Ohdo, S

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 726 150289 2024.9 （ ISSN:0006-291X eISSN:1090-2104 ）

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Language：English Publisher：Biochemical and Biophysical Research Communications

Among the various RNA modifications, adenosine-to-inosine RNA editing, catalyzed by adenosine deaminase acting on RNA (ADAR) family, ADAR1 and ADAR2, is the most common nucleotide conversion in mammalian cells. The pathological relevance of ADAR expression has been highlighted in recent human genetic studies. Low expression of the ADAR2 gene is correlated with a poor prognosis in breast cancer patients, but the underlying mechanism remains enigmatic. In this study, we constructed Adar2-knockdown (Adar2-KD) murine breast cancer 4T1 cells and observed their reduced susceptibility to chemotherapeutic drug doxorubicin. Downregulation of ADAR2 induced the expression of P-glycoprotein (P-gp), leading to a reduction in the intracellular accumulation of doxorubicin. The upregulation of P-gp occurred at the post-transcriptional level due to the decreased miR-195a-3p function. The search for the underlying cause of the induction of P-gp expression in Adar2-KD 4T1 cells led to the identification of circular RNA (circRNA) circHif1a as a sponge for miR-195a-3p. The enhanced expression of circHif1a inhibited miR-195a-3p function, resulting in the upregulation of P-gp expression. These results suggest that ADAR2 acts as a suppressor of circHif1a biogenesis and then allows miR-195a-3p to interfere with P-gp translation. Our findings may help to improve drug efficacy by clarifying the mechanism of chemoresistance in breast cancer.

DOI： 10.1016/j.bbrc.2024.150289

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Epigenetic repression of de novo cysteine synthetases induces intra-cellular accumulation of cysteine in hepatocarcinoma by up-regulating the cystine uptake transporter xCT

Tomoaki Yamauchi, Yumi Okano, Daishu Terada, Sai Yasukochi, Akito Tsuruta, Yuya Tsurudome, Kentaro Ushijima, Naoya Matsunaga, Satoru Koyanagi, Shigehiro Ohdo

Cancer & Metabolism 12 ( 1 ) 23 2024.8 （ ISSN:2049-3002 eISSN:2049-3002 ）

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Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

DOI： 10.1186/s40170-024-00352-4

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Other Link： https://link.springer.com/article/10.1186/s40170-024-00352-4/fulltext.html
Inhibition of G protein-coupled receptor 68 using homoharringtonine attenuates chronic kidney disease-associated cardiac impairment Reviewed

Yuya Yoshida, Kohei Fukuoka, Miyu Sakugawa, Masayuki Kurogi, Kengo Hamamura, Keika Hamasaki, Fumiaki Tsurusaki, Kurumi Sotono, Takumi Nishi, Taiki Fukuda, Taisei Kumamoto, Kosuke Oyama, Takashi Ogino, Akito Tsuruta, Kouta Mayanagi, Tomohiro Yamashita, Hiroyuki Fuchino, Nobuo Kawahara, Kayo Yoshimatsu, Hitomi Kawakami, Satoru Koyanagi, Naoya Matsunaga, Shigehiro Ohdo

Translational Research 269 31 - 46 2024.7 （ ISSN:1931-5244 eISSN:1878-1810 ）

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DOI： 10.1016/j.trsl.2024.02.004

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Dosing time-dependent difference in the suppressive effect of empagliflozin on the development of mechanical pain hypersensitivity in diabetic mice. Reviewed International journal

Ai Sato, Sai Yasukochi, Naho Iwanaka, Tomoaki Yamauchi, Akito Tsuruta, Satoru Koyanagi, Shigehiro Ohdo

The Journal of pharmacology and experimental therapeutics 390 ( 2 ) 177 - 185 2024.7 （ ISSN:00223565 ）

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A problem for patients with diabetes is the rise of complications, such as peripheral neuropathy, nephropathy and retinopathy. Among them, peripheral neuropathy, characterized by numbness and/or hypersensitivity to pain in the extremities, is likely to develop in the early stages of diabetes. Empagliflozin (EMPA), a sodium-glucose cotransporter-2 inhibitor, exerts hypoglycemic effects by preventing glucose reabsorption in proximal tubular cells. EMPA can improve cardiovascular and renal outcomes in diabetic patients, but its suppressive effect on the development of diabetic neuropathy remains unclear. In this study, we demonstrated that optimizing the dosing schedule of EMPA suppressed the development of pain hypersensitivity in streptozotocin (STZ)-induced diabetic model mice maintained under standardized light/dark cycle conditions. A single intraperitoneal administration of STZ to mice induced hyperglycemia accompanied by pain hypersensitivity. Although EMPA did not exert anti-hypersensitivity effect on STZ-induced diabetic mice after the establishment of neuropathic pain, the development of pain hypersensitivity in the diabetic mice was significantly suppressed by daily oral administration of EMPA at the beginning of the dark phase. On the other hand, the suppressive effect was not observed when EMPA was administered at the beginning of the light phase. The hypoglycemic effect of EMPA and its stimulatory effect on urinary glucose excretion were also enhanced by the administration of the drug at the beginning of the dark phase. Nocturnal mice consumed their food mainly during the dark phase. Our results support the notion that morning administration of EMPA may be effective in suppressing the development of peripheral neuropathy in diabetic patients. Significance Statement Empagliflozin, a sodium-glucose cotransporter-2 inhibitor suppressed the development of neuropathic pain hypersensitivity in streptozotocin-induced diabetic model mice in a dosing time-dependent manner.

DOI： 10.1124/jpet.123.001856

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Circadian rhythms in CYP2A5 expression underlie the time-dependent effect of tegafur on breast cancer Reviewed International journal

Yuya Yoshida Taiki Fukuda Tomohito Tanihara Naoki Nishikawa Serina Iwasa Satoka Adachi Orion Zaitsu Yuma Terada Ryotaro Tsukamoto Hideki Shimoshikiryo Kohei Fukuoka Fumiaki Tsurusaki Kengo Hamamura Kosuke Oyama Akito Tsuruta Satoru Koyanagi Naoya Matsunaga Shigehiro Ohdo

Biochemical and Biophysical Research Communications 708 149813 - 149813 2024.5 （ ISSN:0006-291X eISSN:1090-2104 ）

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Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV

DOI： 10.1016/j.bbrc.2024.149813

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Prostaglandin F2α Affects the Cycle of Clock Gene Expression and Mouse Behavior. Reviewed International journal

Yuya Tsurudome Yuya Yoshida Kengo Hamamura Takashi Ogino Sai Yasukochi Shinobu Yasuo Ayaka Iwamoto Tatsuya Yoshihara Tomoaki Inazumi Soken Tsuchiya Toru Takeo Naomi Nakagata Shigekazu Higuchi Yukihiko Sugimoto Akito Tsuruta Satoru Koyanagi Naoya Matsunaga Shigehiro Ohdo

International journal of molecular sciences 25 ( 3 ) 2024.2 （ ISSN:1661-6596 eISSN:1422-0067 ）

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Prostaglandins are bioactive compounds, and the activation of their receptors affects the expression of clock genes. However, the prostaglandin F receptor (Ptgfr) has no known relationship with biological rhythms. Here, we first measured the locomotor period lengths of Ptgfr-KO (B6.129-Ptgfrtm1Sna) mice and found that they were longer under constant dark conditions (DD) than those of wild-type (C57BL/6J) mice. We then investigated the clock gene patterns within the suprachiasmatic nucleus in Ptgfr-KO mice under DD and observed a decrease in the expression of the clock gene cryptochrome 1 (Cry1), which is related to the circadian cycle. Moreover, the expression of Cry1, Cry2, and Period2 (Per2) mRNA were significantly altered in the mouse liver in Ptgfr-KO mice under DD. In the wild-type mouse, the plasma prostaglandin F2α (PGF2α) levels showed a circadian rhythm under a 12 h cycle of light-dark conditions. In addition, in vitro experiments showed that the addition of PTGFR agonists altered the amplitude of Per2::luc activity, and this alteration differed with the timing of the agonist addition. These results lead us to hypothesize that the plasma rhythm of PGF2α is important for driving clock genes, thus suggesting the involvement of PGF2α- and Ptgfr-targeting drugs in the biological clock cycle.

DOI： 10.3390/ijms25031841

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Inhibition of G protein-coupled receptor 68 using homoharringtonine attenuates chronic kidney disease-associated cardiac impairment Reviewed International journal

Yuya Yoshida Kohei Fukuoka Miyu Sakugawa Masayuki Kurogi Kengo Hamamura Keika Hamasaki Fumiaki Tsurusaki Kurumi Sotono Takumi Nishi Taiki Fukuda Taisei Kumamoto Kosuke Oyama Takashi Ogino Akito Tsuruta Kouta Mayanagi Tomohiro Yamashita Hiroyuki Fuchino Nobuo Kawahara Kayo Yoshimatsu Hitomi Kawakami Satoru Koyanagi Naoya Matsunaga Shigehiro Ohdo

Translational Research 2024.2

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DOI： https://doi.org/10.1016/j.trsl.2024.02.004
Time-dependent differences in vancomycin sensitivity of macrophages underlie vancomycin-induced acute kidney injury Reviewed International journal

Yuya Yoshida Taiki Fukuda Kohei Fukuoka Toshitaka Nagayama Tomohito Tanihara Naoki Nishikawa Kaita Otsuki Yuma Terada Kengo Hamamura Kosuke Oyama Akito Tsuruta Kota Mayanagi Satoru Koyanagi Naoya Matsunaga Shigehiro Ohdo

Journal of Pharmacology and Experimental Therapeutics 2024.1

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Suppression of neuropathic pain in the circadian clock–deficient Per2m/m mice involves up-regulation of endocannabinoid system Reviewed International journal

2024.1

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Oral administration of vancomycin alleviates heart failure triggered by chronic kidney disease Reviewed International journal

Kohei Fukuoka, Yuya Yoshida, Kurumi Sotono, Naoki Nishikawa, Kengo Hamamura, Kosuke Oyama, Akito Tsuruta, Kota Mayanagi, Satoru Koyanagi, Naoya Matsunaga, Shigehiro Ohdo

Biochemical and Biophysical Research Communications 675 92 - 98 2023.10 （ ISSN:0006-291X eISSN:1090-2104 ）

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Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV

DOI： 10.1016/j.bbrc.2023.07.015

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Modulation of cell physiology by bispecific nanobodies enabling changes in the intracellular localization of organelle proteins Reviewed International journal

Akito Tsuruta, Daiki Kanetani, Yuki Shiiba, Takuto Inoki, Yuya Yoshida, Naoya Matsunaga, Satoru Koyanagi, Shigehiro Ohdo

Biochemical Pharmacology 215 115708 - 115708 2023.9 （ ISSN:0006-2952 eISSN:1873-2968 ）

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Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV

DOI： 10.1016/j.bcp.2023.115708

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Inhibition of tumor-derived CCL2 expression attenuates tactile allodynia in NCTC 2472 fibrosarcoma-inoculated mice. Reviewed International journal

Marie Taniguchi, Sai Yasukochi, Wakaba Yamakawa, Yuya Tsurudome, Akito Tsuruta, Michiko Horiguchi, Kentaro Ushijima, Tomohiro Yamashita, Naoya Shindo, Akio Ojida, Naoya Matsunaga, Satoru Koyanagi, Shigehiro Ohdo

Molecular pharmacology 104 ( 2 ) 73 - 79 2023.5 （ ISSN:0026-895X eISSN:1521-0111 ）

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Neuropathic pain associated with cancers is caused by tumor growth compressing and damaging nerves, which would also be enhanced by inflammatory factors through sensitizing nociceptor neurons. One troublesome hallmark symptom of neuropathic pain is hypersensitivity to innocuous stimuli, a condition known as "tactile allodynia" which is often refractory to NSAIDs and opioids. The involvement of chemokine CCL2 (monocyte chemoattractant protein-1) in cancer-evoked neuropathic pain is well established, but opinions remain divided as to whether CCL2 is involved in the production of tactile allodynia with tumor growth. In this study, we constructed Ccl2 knockout NCTC2472 (Ccl2-KO NCTC) fibrosarcoma cells and conducted pain behavioral test using Ccl2-KO NCTC-implanted mice. Implantation of naïve NCTC cells around the sciatic nerves of mice produced tactile allodynia in the inoculated paw. Although the growth of Ccl2 KO NCTC-formed tumors was comparable to that of naïve NCTC-formed tumors, Ccl2-KO NCTC-bearing mice failed to show tactile pain hypersensitivity, suggesting the involvement of CCL2 in cancer-induced allodynia. Subcutaneous administration of controlled-release nanoparticles containing CCL2 expression inhibitor NS-3-008 significantly attenuated tactile allodynia in naïve NCTC-bearing mice accompanied by a reduction of CCL2 content in tumor masses. Our present findings suggest that inhibition of CCL2 expression in cancer cells is useful strategy to attenuate tactile allodynia induced by tumor growth. Development of a controlled release system of CCL2 expression inhibitor may be a preventive option for the treatment of cancer-evoked neuropathic pain. Significance Statement The blockade of chemokine/receptor signaling, particularly for C-C motif chemokine ligands 2 (CCL2) and its high-affinity receptor CCR2, has been implicated to attenuate cancer-induced inflammatory and nociceptive pain. This study demonstrated that continuous inhibition of CCL2 production from cancer cells also prevents the development of tactile allodynia associated with tumor growth. Development of controlled release system of CCL2 expression inhibitor may be a preventative option for management of cancer-evoked tactile allodynia.

DOI： 10.1124/molpharm.123.000690

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Senescence-induced alteration of circadian phagocytic activity of retinal pigment epithelium cell line ARPE-19 Reviewed International journal

Ken-ichi Hashikawa, Akito Tsuruta, Wakaba Yamakawa, Sai Yasukochi, Satoru Koyanagi, Shigehiro Ohdo

Biochemical and Biophysical Research Communications 658 88 - 96 2023.5 （ ISSN:0006-291X eISSN:1090-2104 ）

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DOI： 10.1016/j.bbrc.2023.03.070

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Fluorescence-Based Detection of Fatty Acid β-Oxidation in Cells and Tissues Using Quinone Methide-Releasing Probes Reviewed International journal

Shohei Uchinomiya, Tomoki Nagaura, Mark Weber, Yuya Matsuo, Naoki Zenmyo, Yuya Yoshida, Akito Tsuruta, Satoru Koyanagi, Shigehiro Ohdo, Naoya Matsunaga, Akio Ojida

Journal of the American Chemical Society 145 ( 14 ) 8248 - 8260 2023.4 （ ISSN:0002-7863 eISSN:1520-5126 ）

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Language：English Publishing type：Research paper (scientific journal) Publisher：American Chemical Society (ACS)

DOI： 10.1021/jacs.3c02043

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Ternary catalytic α-deuteration of carboxylic acids Reviewed International journal

T. Tanaka, Y. Koga, Y. Honda, A. Tsuruta, N. Matsunaga, S. Koyanagi, S. Ohdo, R. Yazaki & T. Ohshima

Nature Synthesis 1 ( 10 ) 824 - 830 2022.10 （ eISSN:2731-0582 ）

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DOI： 10.1038/s44160-022-00139-9

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Other Link： https://www.nature.com/articles/s44160-022-00139-9
Ternary catalytic α-deuteration of carboxylic acids Reviewed International journal

2022.9

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RNA editing enzyme ADAR1 controls miR-381-3p-mediated expression of multidrug resistance protein MRP4 via regulation of circRNA in human renal cells. Reviewed International journal

Yuji Omata, Maseri Okawa, Mai Haraguchi, Akito Tsuruta, Naoya Matsunaga, Satoru Koyanagi, Shigehiro Ohdo

The Journal of biological chemistry 298 ( 8 ) 102184 - 102184 2022.8 （ ISSN:00219258 eISSN:1083-351X ）

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Multidrug resistance-associated protein 4 (MRP4), a member of the C subfamily of ATP-binding cassette transporters, is highly expressed in the kidneys of mammals and is responsible for renal elimination of numerous drugs. Adenosine deaminase acting on RNA 1 (ADAR1) has been reported to regulate gene expression by catalyzing adenosine-to-inosine RNA editing reactions; however, potential roles of ADAR1 in the regulation of MRP4 expression have not been investigated. In this study, we found that downregulation of ADAR1 increased the expression of MRP4 in human renal cells at the posttranscriptional level. Luciferase reporter assays and microarray analysis revealed that downregulation of ADAR1 reduced the levels of microRNA miR-381-3p, which led to the corresponding upregulation of MPR4 expression. Circular RNAs (circRNAs) are a type of closed-loop endogenous noncoding RNAs that play an essential role in gene expression by acting as miRNA sponges. We demonstrate that ADAR1 repressed the biogenesis of circRNA circHIPK3 through its adenosine-to-inosine RNA editing activity, which altered the secondary structure of the precursor of circHIPK3. Furthermore, in silico analysis suggested that circHIPK3 acts as a sponge of miR-381-3p. Indeed, we found overexpression of circHIPK3 induced the expression of MRP4 through its interference with miR-381-3p. Taken together, our study provides novel insights into regulation of the expression of xenobiotic transporters through circRNA expression by the RNA editing enzyme ADAR1.

DOI： 10.1016/j.jbc.2022.102184

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Diurnal Expression of PD-1 on Tumor-Associated Macrophages Underlies the Dosing Time-Dependent Antitumor Effects of the PD-1/PD-L1 Inhibitor BMS-1 in B16/BL6 Melanoma-Bearing Mice

Tsuruta, A; Shiiba, Y; Matsunaga, N; Fujimoto, M; Yoshida, Y; Koyanagi, S; Ohdo, S

MOLECULAR CANCER RESEARCH 20 ( 6 ) 972 - 982 2022.6 （ ISSN:1541-7786 eISSN:1557-3125 ）

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DOI： 10.1158/1541-7786.MCR-21-0786

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Diurnal Expression of PD-1 on Tumor-Associated Macrophages Underlies the Dosing Time-Dependent Antitumor Effects of the PD-1/PD-L1 Inhibitor BMS-1 in B16/BL6 Melanoma-Bearing Mice. Reviewed International journal

Akito Tsuruta, Yuki Shiiba, Naoya Matsunaga, Marina Fujimoto, Yuya Yoshida, Satoru Koyanagi, Shigehiro Ohdo

Molecular cancer research : MCR 20 ( 6 ) 972 - 982 2022.6

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Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

Cancer cells have acquired several pathways to escape from host immunity in the tumor microenvironment. Programmed death 1 (PD-1) receptor and its ligand PD-L1 are involved in the key pathway of tumor immune escape, and immune checkpoint therapy targeting PD-1 and PD-L1 has been approved for the treatment of patients with certain types of malignancies. Although PD-1 is a well-characterized receptor on T cells, the immune checkpoint receptor is also expressed on tumor-associated macrophages (TAM), a major immune component of the tumor microenvironment. In this study, we found significant diurnal oscillation in the number of PD-1-expressing TAMs collected from B16/BL6 melanoma-bearing mice. The levels of Pdcd1 mRNA, encoding PD-1, in TAMs also fluctuated in a diurnal manner. Luciferase reporter and bioluminescence imaging analyses revealed that a NF-κB response element in the upstream region of the Pdcd1 gene is responsible for its diurnal expression. A circadian regulatory component, DEC2, whose expression in TAMs exhibited diurnal oscillation, periodically suppressed NF-κB-induced transactivation of the Pdcd1 gene, resulting in diurnal expression of PD-1 in TAMs. Furthermore, the antitumor efficacy of BMS-1, a small molecule inhibitor of PD-1/PD-L1, was enhanced by administering it at the time of day when PD-1 expression increased on TAMs. These findings suggest that identification of the diurnal expression of PD-1 on TAMs is useful for selecting the most appropriate time of day to administer PD-1/PD-L1 inhibitors. IMPLICATIONS: Selecting the most appropriate dosing time of PD-1/PD-L1 inhibitors may aid in developing cancer immunotherapy with higher efficacy.

DOI： 10.1158/1541-7786.MCR-21-0786

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Diurnal Expression of PD-1 on Tumor-Associated Macrophages Underlies the Dosing Time-Dependent Antitumor Effects of the PD-1/PD-L1 Inhibitor BMS-1 in B16/BL6 Melanoma-Bearing Mice.

Tsuruta A, Shiiba Y, Matsunaga N, Fujimoto M, Yoshida Y, Koyanagi S, Ohdo S

Molecular cancer research : MCR 20 ( 6 ) 972 - 982 2022.6 （ ISSN:1541-7786 ）

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DOI： 10.1158/1541-7786.MCR-21-0786

PubMed
Diurnal Expression of PD-1 on Tumor-Associated Macrophages Underlies the Dosing Time-Dependent Antitumor Effects of the PD-1/PD-L1 Inhibitor BMS-1 in B16/BL6 Melanoma-Bearing Mice

Tsuruta A., Shiiba Y., Matsunaga N., Fujimoto M., Yoshida Y., Koyanagi S., Ohdo S.

Molecular Cancer Research 20 ( 6 ) 972 - 982 2022.6 （ ISSN:15417786 ）

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Publisher：Molecular Cancer Research

Cancer cells have acquired several pathways to escape from host immunity in the tumor microenvironment. Programmed death 1 (PD-1) receptor and its ligand PD-L1 are involved in the key pathway of tumor immune escape, and immune checkpoint therapy targeting PD-1 and PD-L1 has been approved for the treatment of patients with certain types of malignancies. Although PD-1 is a well-characterized receptor on T cells, the immune checkpoint receptor is also expressed on tumor-associated macrophages (TAM), a major immune component of the tumor microenvironment. In this study, we found significant diurnal oscillation in the number of PD-1–expressing TAMs collected from B16/BL6 melanoma-bearing mice. The levels of Pdcd1 mRNA, encoding PD-1, in TAMs also fluctuated in a diurnal manner. Luciferase reporter and bioluminescence imaging analyses revealed that a NF-kB response element in the upstream region of the Pdcd1 gene is responsible for its diurnal expression. A circadian regulatory component, DEC2, whose expression in TAMs exhibited diurnal oscillation, periodically suppressed NF-kB–induced transactivation of the Pdcd1 gene, resulting in diurnal expression of PD-1 in TAMs. Furthermore, the antitumor efficacy of BMS-1, a small molecule inhibitor of PD-1/PD-L1, was enhanced by administering it at the time of day when PD-1 expression increased on TAMs. These findings suggest that identification of the diurnal expression of PD-1 on TAMs is useful for selecting the most appropriate time of day to administer PD-1/PD-L1 inhibitors. Implications: Selecting the most appropriate dosing time of PD-1/ PD-L1 inhibitors may aid in developing cancer immunotherapy with higher efficacy.

DOI： 10.1158/1541-7786.MCR-21-0786

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Diurnal Expression of PD-1 on Tumor-Associated Macrophages Underlies the Dosing Time-Dependent Antitumor Effects of the PD-1/PD-L1 Inhibitor BMS-1 in B16/BL6 Melanoma-Bearing Mice

Tsuruta, A; Shiiba, Y; Matsunaga, N; Fujimoto, M; Yoshida, Y; Koyanagi, S; Ohdo, S

MOLECULAR CANCER RESEARCH 20 ( 6 ) 972 - 982 2022.6 （ ISSN:1541-7786 eISSN:1557-3125 ）

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DOI： 10.1158/1541-7786.MCR-21-0786

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RNA editing enzyme ADAR1 controls miR-381-3p-mediated expression of multidrug resistance protein MRP4 via regulation of circRNA in human renal cells. Reviewed International journal

Omata Y, Okawa M, Haraguchi M, Tsuruta A, Matsunaga N, Koyanagi S, Ohdo S.

journal of biological chemistry 2022.4

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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 Reviewed International journal

Akito Tsuruta, Yuki Shiiba, Naoya Matsunaga, Marina Fujimoto, Yuya Yoshida, Satoru Koyanagi, Shigehiro Ohdo

Molecular cancer research 2022.2

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ビタミンAと免疫細胞に着目した慢性腎臓病時における腎-腸連関機構の解析

福岡航平, 吉田優哉, 西川直希, 松永直哉, 鶴田朗人, 小柳悟, 大戸茂弘

日本臨床薬理学会学術総会抄録集 43 ( 0 ) 2-C-P-084 2022 （ eISSN:24365580 ）

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Language：Japanese Publisher：一般社団法人日本臨床薬理学会

【目的】腎臓は様々な臓器と連関しているため、慢性腎臓病 (CKD)が生体に及ぼす影響は多岐に渡る。その一つとして、腸内細菌が乱れた状態 (ディスバイオシス)が引き起こされることが近年報告されている。腸内細菌はインドキシル硫酸 (IS)等の一部の尿毒症物質の産生源であり、CKDの病態悪化への寄与が疑われているが、具体的な機構は十分に解析されていない。一方で我々は、CKDマウスを用いた解析により、CKD時に肝臓にてビタミンA (VA)の代謝不全が生じることを報告している1,2。VAは腸管免疫を司る重要な分子であるため、CKD時のディスバイオシスへの関与が疑われる。そこで本研究ではVAに着目し、腸内細菌の変容ならびに腸内細菌由来物質の増加機構について解析を行った。【方法】ICRマウスの腎臓を5/6摘出し、その後8週間飼育することでCKDマウス (5/6 Nephrectomy: 5/6Nx)を作製した。また、対照としてSham群を作製し、各種解析を行った。血中の因子測定はLC-MS/MSを用い、タンパク質発現量はウェスタンブロット法を用いて測定した。【結果・考察】まずCKD患者の血清を解析した結果、血中VA濃度と腎障害に相関が認められた。そこでVAと尿毒症物質との関連を明らかにするため、5/6NxマウスにVA不含給餌を行った結果、SCrやBUNは減少しなかったにもかかわらず、IS等の腸内細菌産生尿毒症物質のみ血中濃度が低下することを発見した。この原因を明らかにするため、5/6Nxマウスにおける腸管免疫に着目し解析を行ったところ、VA不含給餌は5/6Nxマウスの腸管内で亢進するIgA分泌を抑制し、菌叢を再変容させることが明らかになった。このことは、5/6NxマウスではVAを介して腸管免疫機能が亢進していることを示唆している。そこで腸管の免疫細胞を対象とした詳細な解析を行った結果、5/6Nxマウスではパイエル板における樹状細胞のレチノイン酸合成能が亢進し、B細胞からIgA産生細胞への分化が促進されることが明らかになった。さらに、阻害剤を用いたこれら経路の抑制は、5/6Nxマウス腸管のIgA量およびIS等の血中濃度を低下させた。【結論】以上の結果より、VAおよび腸管の免疫細胞を介した新たな腎-腸連関機構を解明した。本研究のさらなる解析が、新規治療薬の開発に繋がることが期待される。【参考文献】1. Yoshida Y, Matsunaga M, Ohdo S, et al., Nat. Commun. 2021.2. Hamamura K, Matsunaga M, Ohdo S, et al., J. Bio. Chem. 2016.

DOI： 10.50993/jsptsuppl.43.0_2-c-p-084

CiNii Research
RNA editing enzyme ADAR1 governs the circadian expression of P-glycoprotein in human renal cells by regulating alternative splicing of the ABCB1 gene Reviewed International journal

#Yuji Omata, #Tomoaki Yamauchi, @Akito Tsuruta, @Naoya Matsunaga, @Satoru Koyanagi, @Shigehiro Ohdo

Journal of biological chemistry 2021.6

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DOI： 10.1016/j.jbc.2021.100601
Alteration of circadian machinery in monocytes underlies chronic kidney disease-associated cardiac inflammation and fibrosis Reviewed International journal

@Yuya Yoshida, @Naoya Matsunaga, #Takaharu Nakao, #Kengo Hamamura, @Hideaki Kondo, @Tomomi Ide, @Hiroyuki Tsutsui, @Akito Tsuruta, #Masayuki Kurogi, @Michio Nakaya, @Hitoshi Kurose, @Satoru Koyanagi, @Shigehiro Ohdo.

Nature communications 2021.5

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DOI： 10.1038/s41467-021-23050-x
Post-transcriptional repression of circadian component CLOCK regulates cancer-stemness in murine breast cancer cells Reviewed International journal

#Takashi Ogino, @Naoya Matsunaga, #Takahiro Tanaka, #Tomohito Tanihara, @Hideki Terajima, @Hikari Yoshitane, @Yoshitaka Fukada, @Akito Tsuruta, @Satoru Koyanagi, @Shigehiro Ohdo

Elife 2021.4

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DOI： 10.7554/eLife.66155
Circadian expression of Glycoprotein 2 ( Gp2 ) gene is controlled by a molecular clock in mouse Peyer's patches Reviewed International journal

[Naoki Kusunose,Akito Tsuruta,Kengo Hamamura,Yuya Tsurudome,Yuya Yoshida,Takahiro Akamine,Naoya Matsunaga,Satoru Koyanagi,Shigehiro Ohdo]

Genes to cells 2020.4

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DOI： 10.1111/gtc.12758
Fluorescence detection of metabolic activity of the fatty acid beta oxidation pathway in living cells Reviewed International journal

Shohei Uchinomiya,Naoya Matsunaga,Koichiro Kamoda,Ryosuke Kawagoe,Akito Tsuruta,Shigehiro Ohdo,Akio Ojida

Chemical comunications 2020.2

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DOI： 10.1039/c9cc09993j
Epithelial cell adhesion molecule expression in hepatic stem/progenitor cells is controlled by the molecular clock system Reviewed International journal

[Hinako Kimura,Naoya Matsunaga,Keisuke Kakimoto,Miyako Watanabe,Akito Tsuruta,Naoki Kusunose,Shoya Shiromizu,Satoru Koyanagi,Shigehiro Ohdo]

Biochemical and biophysical research communications 2018.9

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DOI： 10.1016/j.bbrc.2018.06.117
Inhibition of G0/G1 Switch 2 Ameliorates Renal Inflammation in Chronic Kidney Disease Reviewed International journal

[Naoya Matsunaga,Eriko Ikeda,Keisuke Kakimoto,Miyako Watanabe,Naoya Shindo,Akito Tsuruta,Hisako Ikeyama,Kengo Hamamura,Kazuhiro Higashi,Tomohiro Yamashita,Hideaki Kondo,Yuya Yoshida,Masaki Matsuda,Takashi Ogino,Kazutaka Tokushige,Kazufumi Itcho,Yoko Furuichi,Takaharu Nakao,Kaori Yasuda,Atsushi Doi,Toshiaki Amamoto,Hironori Aramaki,Makoto Tsuda,Kazuhide Inoue,Akio Ojida,Satoru Koyanagi,Shigehiro Ohdo]

EBioMedicine 2016.11

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DOI： 10.1016/j.ebiom.2016.10.008
Circadian Clock in a Mouse Colon Tumor Regulates Intracellular Iron Levels to Promote Tumor Progression Reviewed International journal

Fumiyasu Okazaki,Naoya Matsunaga,Hiroyuki Okazaki,Hiroki Azuma,Kengo Hamamura,Akito Tsuruta,Yuya Tsurudome,Takashi Ogino,Yukinori Hara,Takuya Suzuki,Kenji Hyodo,Hiroshi Ishihara,Hiroshi Kikuchi,Hideto To,Hironori Aramaki,Satoru Koyanagi,Shigehiro Ohdo

Journal of biological chemistry 2016.3

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DOI： 10.1074/jbc.m115.713412

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Dosing time dependent changes in efficacy of immune checkpoint inhibitor based on the circadian rhythm of PD-1 expression on macrophage International conference

2024.9

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SGLT2阻害薬エンパグリフロジンの投薬時刻依存的な糖尿病性末梢神経障害発症の抑制効果に及ぼす摂食時刻の影響解析

佐藤愛、岩中菜穂、安河内冴、山内智暁、鶴田朗人、小柳悟、大戸茂弘

日本薬学会第144年会（横浜） 2024.3

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時計遺伝子の機能不全マウスを用いた神経障害性疼痛の発症抑制メカニズムの解析

山川稚葉、安河内冴、鶴留優也、牛島健太郎、鶴田朗人、松永直哉、小柳悟、大戸茂弘

日本薬学会第144年会（横浜） 2024.3

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Mechanism and pathological significance of cysteine metabolic reprogramming associated with hepatocarcinogenesis

YamauchiTomoaki,YumiOkano,DaisyuTerada,AkitoTsuruta ,SatoruKoyanagi, Shigehiro Ohdo

2023.12

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RNA編集酵素による「環状RNA-microRNA経路」を介したヒト腎尿細管上皮細胞における薬物排泄トランスポーターMRP4発現制御機構の解析

小俣裕司、大川ませ梨、原口真依、鶴田朗人、松永直哉、小柳悟、大戸茂弘

第44回日本臨床薬理学会学術総会 2023.12

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肝腫瘍組織における細胞外からのシステイン供給増加の病態学的意義の解析

岡野佑美, 山内智暁, 吉田優哉, 鶴田朗人, 松永直哉, 小柳悟, 大戸茂弘

第97回日本薬理学会年会 2023.12

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RNA編集酵素による「環状RNA-microRNA経路」を介したヒト腎尿細管上皮細胞における薬物排泄トランスポーターMRP4発現制御機構の解析

小俣裕司, 大川ませ梨, 原口真依, 鶴田朗人, 松永直哉, 小柳悟, 大戸茂弘

日本臨床薬理学会学術総会抄録集 2023.12 (一社)日本臨床薬理学会

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肝細胞のがん化に伴うシステイン代謝変容のメカニズムと病態学的意義の解析

⼭内智暁，岡野佑美，寺⽥⼤修，鶴⽥朗⼈，⼩柳悟，⼤⼾茂弘

第97回日本薬理学会年会 2023.12

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微弱電流刺激がマクロファージ貪食能に及ぼす影響の解析

鶴崎文彬, 吉田優哉, 濱崎景佳, 谷原智仁, 橋本優希, 福田大輝, 鶴田朗人, 小山浩舗, 濱村賢吾, 小柳悟, 松永直哉, 大戸茂弘

日本臨床薬理学会学術総会抄録集 2023.12 (一社)日本臨床薬理学会

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新規炎症関連タンパク質NPIPの機能に着目したマクロファージ分化機構の解析

石丸和佳, 鶴田朗人, 吉田優哉, 松永直哉, 小柳悟, 大戸茂弘

日本臨床薬理学会学術総会抄録集 2023.12 (一社)日本臨床薬理学会

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Pathological significance of extracellular cysteine supply in hepatic tumor tissues

Okano Yumi, Tomoaki Yamauchi, Yuya Yoshida, Akito Tsuruta, Naoya Matsunaga, Satoru Koyanagi, Shigehiro Ohdo

2023.12

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薬物代謝酵素CYP 3A4の概日リズム制御機構の解析

大川ませ梨、小俣裕司、原口真依、吉田優哉、鶴田朗人、松永直哉、小柳悟、大戸茂弘)

第44回日本臨床薬理学会学術総会 2023.12

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新規炎症関連タンパク質NPIPに着目したマクロファージ分化機構の解析

石丸和佳、鶴田朗人、吉田優哉、松永直哉、小柳悟、大戸茂弘

第44回日本臨床薬理学会学術総会 2023.12

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GPR68を標的とした慢性腎臓病誘発性の心炎症・線維化抑制化合物の探索

吉田優哉, 佐久川未有, 福岡航平, 外野来海, 谷原智仁, 西川直希, 鶴田朗人, 小山浩舗, 濱村賢吾, 小柳悟, 松永直哉, 大戸茂弘

日本臨床薬理学会学術総会 2023.12 (一社)日本臨床薬理学会

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糖尿病性末梢神経障害疼痛に対するSGLT2阻害薬エンパグリフロジンの至適投薬タイミングに関する検討

佐藤愛、安河内　冴、山内　智暁、鶴田　朗人、小柳　悟、大戸　茂弘

2023.11

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HER2標的型抗体-薬物複合体トラスツズマブデルクステカンの抗腫瘍効果を増強する既承認薬の探索

原口真依、小俣裕司、大川ませ梨、山下智大、鶴田朗人、小柳悟、大戸茂弘

第40回日本薬学会九州山口支部大会 2023.11

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腫瘍微小環境中のCD4⁺T細胞におけるCXCR4機能の解析

谷口葵、鶴田朗人、平岡恭羽、小柳悟、大戸茂弘

第40回日本薬学会九州山口支部大会 2023.11

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慢性掻痒モデル動物における痒み行動の概日リズム制御メカニズムの解析

中村理紗子、安河内冴、鶴田朗人、小柳悟、大戸茂弘

第40回日本薬学会九州山口支部大会 2023.11

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Venue：福岡
腫瘍関連マクロファージのPD-1膜発現概日リズムに着目した時間薬理学的検討 Invited

鶴田朗人, 松永直哉, 吉田優哉, 小柳悟, 大戸茂弘

生体膜と薬物の相互作用シンポジウム 2023.10

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NAT10-mediated JARID2 stabilization regulates stemness properties of glioblastoma cells

2023.9

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RNA編集酵素ADAR2による「環状RNA-microRNA経路」を介した乳がん細胞の抗がん剤耐性獲得メカニズムの解析

小俣裕司、原口真依、吉永彩恵、荻野敬史、大川ませ梨、鶴田朗人、小柳悟、大戸茂弘

第22回次世代を担う若手のためのファーマ・バイオフォーラム2023 2023.9

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RNA editing enzyme ADAR2 is involved in P-glycoprotein-mediated doxorubicin resistance in murine breast cancer cells via circRNA-miRNA pathway

Yuji Omata, Mai Haraguchi, Sae Yoshinaga, Tkashi Ogino, Maseri Okawa, Akito Tsuruta, Satoru Koyanagi, Shigehiro Ohdoo

2023 International Joint meeting of the 23rd International conference on cytochrome p450 and the 38th annual meeting of the japanese society for the study of xenobiotics in shizuoka 2023.9

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RNA編集酵素ADAR2による「環状RNA-microRNA経路」を介した乳がん細胞抗がん剤耐性獲得メカニズムの解析

小俣裕司、原口真依、吉永彩恵、荻野敬史、大川ませ梨、鶴田朗人、小柳悟、大戸茂弘

次世代を担う若手ファーマバイオフォーラム 2023.9

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細胞のがん化に伴うシステイン代謝変容機構と病態学的意義の解析

山内智暁、岡野佑美、寺田大修、鶴田朗人、小柳悟、大戸茂弘

次世代を担う若手ファーマバイオフォーラム 2023.9

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NAT10-mediated JARID2 stabilization regulates stemness properties of glioblastoma cells

Takuto Inoki, Akito Tsuruta, Yoshinori Masakado, Yuya Yoshida, Naoya Matsunaga, Satoru Koyanagi, Shigehiro Ohdo

2023.9

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N-acetyl transferase 10 enhances glioblastoma malignancy via polycomb complex 2

Akito Tsuruta, Takuto Inoki, Yuya Yoshida Naoya Matsunaga, Satoru Koyanagi, Shigehiro Ohdo

2023.9

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N-acetyl transferase 10はPRC2複合体の制御を介してグリオーマの悪性化を促進する(N-acetyl transferase 10 enhances glioblastoma malignancy via regulation of polycomb complex 2)

鶴田朗人, 松永直哉, 吉田優哉, 小柳悟, 大戸茂弘

日本癌学会総会記事 2023.9 (一社)日本癌学会

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RNAアセチル化を標的とした新規非アルコール性脂肪肝炎治療法の構築

猪木拓人、鶴田朗人、吉田優哉、松永直哉、小柳悟、大戸茂弘

日本薬剤学会第38年会　SNPEE2023 2023.5

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グリオブラストーマの悪性度に及ぼすNAT10を介したmRNAアセチル化の影響解析

猪木拓人、鶴田朗人、正門佳法、吉田優哉、松永直哉、小柳悟、大戸茂弘

日本薬学会第143年会 2023.3

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Venue：北海道
RNA編集酵素ADAR1による「環状RNA」生成制御を介したヒト腎尿細管上皮細胞における薬物排泄トランスポーターMRP4発現制御機構の解析

小俣裕司、大川ませ梨、原口真依、鶴田朗人、松永直哉、小柳悟、大戸茂弘

日本薬学会第143年会参加 2023.3

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概日変動メカニズムに基づいたがん疼痛の病態解析

安河内冴、山川稚葉、鶴田朗人、橋本優希、中村理紗子、松永直哉、小柳悟、大戸茂弘

日本薬学会第143年会 2023.3

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心不全研究　腎障害時の心臓の炎症は単球伝達時計の変容により引き起こされる

大戸茂弘, 吉田優哉, 鶴田朗人, 松永直哉, 小柳悟

血管 2023.1 日本心脈管作動物質学会

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ビタミンAと免疫細胞に着目した慢性腎臓病時における腎-腸連関機構の解析

福岡航平, 吉田優哉, 西川直希, 松永直哉, 鶴田朗人, 小柳悟, 大戸茂弘

日本臨床薬理学会学術総会抄録集 2022.12 (一社)日本臨床薬理学会

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ビタミンAと免疫細胞に着目した慢性腎臓病時における腎-腸連関機構の解析

福岡航平, 吉田優哉, 西川直希, 松永直哉, 鶴田朗人, 小柳悟, 大戸茂弘

日本臨床薬理学会学術総会 2022.12

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マクロファージのPD-1発現概日変動に合わせた免疫チェックポイント阻害剤の投薬時刻の最適化(Optimization of dosing time of immune checkpoint inhibitor based on circadian rhythm of PD-1 expression on macrophage)

鶴田朗人, 松永直哉, 吉田優哉, 小柳悟, 大戸茂弘

日本癌学会総会記事 2022.9 (一社)日本癌学会

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概日リズム変調時における神経障害性疼痛の発症抑制メカニズムの解析

山川稚葉, 安河内冴, 鶴留優也, 牛島健太郎, 鶴田朗人, 松永直哉, 小柳悟, 大戸茂弘

日本薬学会年会 142年会 2022.3

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カルボン酸の触媒的α-重水素化反応

田中津久志, 鶴田朗人, 松永直哉, 小柳悟, 大戸茂弘, 矢崎亮, 大嶋孝志

日本薬学会年会要旨集 2022.3 (公社)日本薬学会

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概日リズム変調時における神経障害性疼痛の発症抑制メカニズムの解析

山川稚葉, 安河内冴, 鶴留優也, 牛島健太郎, 鶴田朗人, 松永直哉, 小柳悟, 大戸茂弘

日本薬学会年会 142年会 2022.3

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概日リズム変調時における神経障害性疼痛の発症抑制メカニズムの解析

山川稚葉, 安河内冴, 鶴留優也, 牛島健太郎, 鶴田朗人, 松永直哉, 小柳悟, 大戸茂弘

日本薬学会年会要旨集 2022.3 (公社)日本薬学会

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Event date： 2022.3

Language：Japanese
概日時計の分子機構を基盤とした心-腎連関機構の解析

吉田優哉、松永直哉、鶴田朗人、小柳悟、大戸茂弘

第42回日本臨床薬理学会学術総会 2021.12

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Event date： 2021.12
フェブキソスタットのBCRP機能阻害によるスルファサラジンの消化管吸収改善と末梢神経障害性疼痛緩和作用に及ぼす効果

安河内冴、山川稚葉、山内智暁、小俣裕司、鶴田朗人、松永直哉、小柳悟、大戸茂弘

日本薬物動態学会 2021.11

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Event date： 2021.11
神経障害性疼痛の発症における時計遺伝子Period２の機能解析

山川稚葉、安河内冴、鶴留優也、牛島健太郎、鶴田朗人、松永直哉、小柳悟、大戸茂弘

第38回日本薬学会九州山口支部大会 2021.11

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Event date： 2021.11
タモキシフェン誘発性肝障害の時間薬理学的研究

西川直希、吉田優哉、松永直哉、鶴田朗人、小柳悟、大戸茂弘

日本薬学会九州山口支部大会、第38回 2021.11

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Event date： 2021.11
RNA編集酵素ADAR1によるヒト腎近位尿細管上皮細胞でのP糖タンパク質発現の概日リズム制御

小俣裕司、大川ませ梨、鶴田朗人、松永直哉、小柳悟、大戸茂弘

日本薬物動態学会第36回年会 2021.11

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Event date： 2021.11
Disruption of circadian metabolic regulation of cysteine contributes to the rapid growth and malignancy of murine hepatic cancer cells

2021.10

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Event date： 2021.10
疼痛増悪分子SGK-1を標的としたスルファサラジンによる神経障害性疼痛に対する新規治療戦略の構築

安河内冴、楠瀬直喜、山内智暁、山川稚葉、小俣裕司、鶴田朗人、松永直哉、小柳悟、大戸茂弘

医療薬学フォーラム2021 第29回クリニカルファーマシーシンポジウム 2021.7

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Event date： 2021.7
小俣裕司、山内智暁、鶴田朗人、松永直哉、小柳悟、大戸茂弘

小俣裕司、山内智暁、鶴田朗人、松永直哉、小柳悟、大戸茂弘

日本薬剤学会第36年会 2021.5

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Event date： 2021.5
RNA編集酵素ADAR1によるヒト腎細胞でのP糖タンパク質発現の概日リズム制御機構

小俣裕司、山内智暁、鶴田朗人、松永直哉、小柳悟、大戸茂弘

日本薬学会第141年会 2021.3

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Event date： 2021.3

Language：Japanese

Country：Japan
がん細胞におけるシスチン取込み卜ランスポーターを標的とした杭がん剤の時間薬理学的検討

山内智暁，楠瀬直喜, 白水翔也，松永直哉, 小柳悟，大戸茂弘

第41回日本臨床薬理学会学術総会 2020.12

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Event date： 2020.12

Country：Japan
慢性腎臓病時に発症する認知機能障害発症機構の解明

松永直哉，古市葉子,　吉田優哉,　鶴田朗人，小柳悟，大戸茂弘

第41回日本臨床薬理学会学術総会 2020.12

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Event date： 2020.12

Country：Japan
概日時計機構を基盤とした慢性腎臓病治療標的タンパクの探索

鶴田朗人, 松永直哉，吉田優哉, 渡邊美弥子, 小柳悟，大戸茂弘

第41回日本臨床薬理学会学術総会 2020.12

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Event date： 2020.12

Country：Japan
難治性ヒ卜乳がん細胞の薬剤抵抗性を改善する化告物の探索

谷尾莉佳, 松永直哉，荻野敬史，岩本真由香, 森謙一郎, 鶴田朗人, 小柳悟，大戸茂弘

第41回日本臨床薬理学会学術総会 2020.12

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Event date： 2020.12

Country：Japan
腎障害誘発性の心炎症、線維化抑制化合物の探索

北川陽也，松永直哉，吉田優哉, 黒木雅礼, 鶴田朗人，小柳悟，大戸茂弘

第41回日本臨床薬理学会学術総会 2020.12

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Event date： 2020.12

Country：Japan
時間薬剤学的アプローチによる神経障害性疼痛に対する鎮痛化合物の探索と新規治療戦略の構築

安河内冴，楠瀬直喜,山内智暁,小俣裕司, 鶴田朗人,松永直哉，小柳悟，大戸茂弘

第41回日本臨床薬理学会学術総会 2020.12

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Event date： 2020.12

Country：Japan
がん幹様細胞における転写因子の発現に着目した難治性乳がんの新規治療法に関する検討

荻野敬史，松永直哉,鶴田朗人，小柳悟，大戸茂弘

第41回日本臨床薬理学会学術総会 2020.12

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Event date： 2020.12

Country：Japan
肝臓がんの発症を抑制する新規抗炎症化合物の探索

椎葉友輝, 松永直哉，鶴田朗人，柿本啓輔, 渡邊美弥子，小柳悟, 大戸茂弘

第41回日本臨床薬理学会学術総会 2020.12

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Event date： 2020.12

Country：Japan
アクアポリン3に着目した皮膚の分子時計機構,

正門佳法,一町和史，松永直哉,鶴田朗人,小柳悟，大戸茂弘

第41回日本臨床薬理学会学術総会 2020.12

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Event date： 2020.12

Country：Japan
パーキンソン病モデルマウスにおける生体リズム障害誘発機構

西川直希，林亜錦，松永直哉,鶴田朗人,小柳悟，大戸茂弘

第41回日本臨床薬理学会学術総会 2020.12

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Event date： 2020.12

Country：Japan
マウス腎がんを対象としたエベ口リムスの時間薬物治療に関する検討

谷原智仁, 岡崎裕之，松永直哉, 鶴田朗人, 小柳悟，大戸茂弘

第41回日本臨床薬理学会学術総会 2020.12

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Event date： 2020.12

Country：Japan
Transferrin修飾liposome製剤を用いた癌の時間治療に関する検討

金谷大騎, 岡崎史泰，松永直哉, 鶴田朗人, 小柳悟，大戸茂弘

第41回日本臨床薬理学会学術総会 2020.12

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Event date： 2020.12

Country：Japan
鎮痛増悪分子SGK-1を標的としたスルファサラジンによる神経障害性疼痛に対する新規治療戦略の構築

安河内冴、楠瀬直喜、山内智暁、山川稚葉、小俣裕司、鶴田朗人、松永直哉、小柳悟、大戸茂弘

次世代を担う若手のための医療薬科学シンポジウム 2020.11

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Event date： 2020.11

Country：Japan
Novel mechanism of promotion in fibrosis of chronic renal disease based on the molecular clock’s work. International conference

2020.10

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Event date： 2020.10

Language：Japanese

Country：Japan
単球に着目した慢性腎臓病時における心臓病態悪化の新規メカニズム解明, 第13回　次世代を担う若手医療薬科学シンポジウム

#吉田優哉,松永直哉,@濵村賢吾,鶴田朗人,小柳悟,大戸茂弘

次世代を担う若手医療薬科学シンポジウム 2020.10

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Event date： 2020.10

Language：Japanese

Country：Japan
体内時計の分子機構に及ぼすマイクロ電流刺激の影響

北城直樹,松永直哉,吉田優哉,鶴田朗人,小柳悟,大戸茂弘

第36回日本薬学会九州支部大会 2020.10

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Event date： 2020.10

Language：Japanese

Country：Japan
がん幹様細胞における転写因子の発現に着目した難治性乳がんの新規治療法に関する検討

荻野敬史,松永直哉,鶴田朗人,小柳悟,大戸茂弘

第36回日本薬学会九州支部大会 2020.10

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Event date： 2020.10

Language：Japanese

Country：Japan
Ccrfを標的とした新規慢性肝炎治療薬の開発

柴田愛実,鶴田朗人,松永直哉,楠瀬直喜,小柳悟,大戸茂弘

第35回日本薬学会九州支部大会 2020.10

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Event date： 2020.10

Language：Japanese

Country：Japan
概日時計の分子機構を基盤にした腫瘍細胞への薬物送達の効率化と新規抗炎症薬の探索

鶴田朗人、松永直哉、楠瀬直喜、小柳悟、大戸茂弘

日本薬剤学会第32年会 2020.10

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Event date： 2020.10

Language：Japanese

Country：Japan
マウス消化管における核酸輸送トランスポーターCNT2 の概日リズム制御機構の解析

Nour JABALLAH,鶴留優也,鶴田朗人,楠瀬直喜,松永直哉,小柳悟,大戸茂弘

2020.10

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Event date： 2020.10

Language：Japanese

Country：Japan
慢性腎臓病モデルマウスにおける分子時計を介した腎-肝-腎連関機構の解明

#中尾崇治,松永直哉,#吉田優也,鶴田朗人,濱村賢吾,近藤英明,小柳悟,大戸茂弘

第11回日本腎臓病薬物治療法学会学術集会 2020.10

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Event date： 2020.10

Language：Japanese

Country：Japan
慢性腎不全時の炎症概日リズムに着目した新規抗炎症化合物の探索

鶴田朗人,松永直哉,吉田優哉,小柳悟,大戸茂弘

日本薬学会第140年会 2020.10

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Event date： 2020.10

Language：Japanese

Country：Japan
薬物代謝酵素CYP3A4の概日リズム制御機構の解析

大川ませ梨, 小俣裕司, 原口真依, 吉田優哉, 鶴田朗人, 松永直哉, 小柳悟, 大戸茂弘

日本臨床薬理学会学術総会抄録集 2024.1 (一社)日本臨床薬理学会

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脂質を見る・捉える革新的な新技術　有機小分子プローブによるミトコンドリア/ペルオキシソーム脂肪酸β酸化の蛍光検出

内之宮祥平, 永浦智樹, 松尾祐治, 鶴田朗人, 吉田優哉, 小柳悟, 大戸茂弘, 松永直哉, 王子田彰夫

脂質生化学研究 2024.5 日本脂質生化学会

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生体リズムに着目したタモキシフェン誘発性肝障害の解析

西川直希, 吉田優哉, 松永直哉, 鶴田朗人, 小柳悟, 大戸茂広

日本薬学会年会要旨集 2022.3 (公社)日本薬学会

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MISC

時計遺伝子の機能不全マウスにおける神経障害性疼痛の発症抑制メカニズムの解析

山川稚葉, 安河内冴, 鶴留優也, 牛島健太郎, 鶴田朗人, 松永直哉, 小柳悟, 大戸茂弘

次世代を担う若手のための創薬・医療薬理シンポジウムプログラム・要旨集 2022 2022

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J-GLOBAL

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Mechanistic analysis for prevention of neuropathic pain development during the disturbance of circadian rhythm

山川稚葉, 安河内冴, 鶴留優也, 牛島健太郎, 鶴田朗人, 松永直哉, 小柳悟, 大戸茂弘

日本薬学会年会要旨集(Web) 142nd 2022 （ ISSN:0918-9823 ）

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J-GLOBAL

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Professional Memberships

日本薬学会
日本薬剤学会
日本臨床薬理学会
日本癌学会
日本薬学会

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日本薬剤学会

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日本臨床薬理学会

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日本癌学会

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Academic Activities

座長

第39回日本薬学会九州山口支部大会 2023.11

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第39回日本薬学会九州山口支部大会

Role(s)： Review, evaluation

2022.11

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Type：Academic society, research group, etc.

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座長

第38回日本薬学会九州山口支部大会（熊本） 2021.11

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Type：Competition, symposium, etc.

Number of participants：500

Research Projects

非天然α-アミノ酸を用いた中分子ペプチド医薬品創成

2023.5

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Authorship：Coinvestigator(s)
腫瘍浸潤T細胞の概日時計機構破綻による腫瘍免疫抑制機構の解明

2023.4 - 2025.3

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Authorship：Principal investigator
腫瘍浸潤T細胞の概日時計機構破綻による腫瘍免疫抑制機構の解明

Grant number：23K14569 2023 - 2024

日本学術振興会科学研究費助成事業若手研究

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Authorship：Principal investigator Grant type：Scientific research funding
腫瘍浸潤T細胞の概日時計機構破綻による腫瘍免疫抑制機構の解明

Grant number：23K14569 2023 - 2024

日本学術振興会科学研究費助成事業若手研究

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Authorship：Principal investigator Grant type：Scientific research funding
ふくおか公衆衛生推進機構　研究奨励賞

2023

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Grant type：Donation
中村奨励金

2021

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Grant type：Donation
腫瘍内に浸潤した免疫細胞中の概日時計機構変容による腫瘍増殖メカニズムの解明

2020.4 - 2023.3

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Authorship：Principal investigator
Tumor immunosuppression by disruption of the circadian clock in tumor-infiltrated immune cells

Grant number：20K16306 2020 - 2022

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Early-Career Scientists

Tsuruta Akito

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Clock genes that control biological clocks are also expressed in immune cells and regulate various immune functions. Alteration of biological clock induces dysregulation of immune functions. In this study, we found that the circadian clock machinery was altered in tumor-associated macrophages (TAMs). This alteration causes the administration-time dependent changes of the effect of immune checkpoint inhibitor (ICI).

CiNii Research
笹川科学研究助成金研究課題：mRNAアセチル化によるWobble塩基対安定化を介したグリオブラストーマ幹細胞性維持機構の解明

2020

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Grant type：Donation
RNAのアセチル化に着目したグリオブラストーマ幹細胞性の制御機構

2019.4 - 2021.3

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Authorship：Principal investigator
RNAのアセチル化に着目したグリオブラストーマ幹細胞性の制御機構

Grant number：19K23891 2019 - 2021

日本学術振興会科学研究費助成事業研究活動スタート支援

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Class subject

薬学基礎実習Ⅳ

2024.6 - 2024.8 Summer quarter
薬学基礎実習IV

2024.4 - 2024.9 First semester
医療薬学演習II

2024.4 - 2024.9 First semester
医療薬学演習I

2024.4 - 2024.9 First semester
薬学基礎実習IV

2024.4 - 2024.9 First semester
薬剤・動態学

2024.4 - 2024.9 First semester
医療薬学演習Ⅱ

2024.4 - 2024.9 First semester
医療薬学演習Ⅰ

2024.4 - 2024.9 First semester
薬剤・動態学

2024.4 - 2024.6 Spring quarter
医療薬学演習II

2023.4 - 2023.9 First semester
医療薬学演習I

2023.4 - 2023.9 First semester
薬学基礎実習Ⅳ

2024.6 - 2024.8 Summer quarter
医療薬学演習Ⅱ

2024.4 - 2024.9 First semester
医療薬学演習Ⅰ

2024.4 - 2024.9 First semester
薬剤・動態学

2024.4 - 2024.6 Spring quarter

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