2023/04/01 更新

写真a

マスムラ マコト
升村 誠
MASUMURA Makoto
所属
地域創生推進機構 特任教授
職名
特任教授
外部リンク

学位

  • 博士(薬学) ( 2002年7月   東京大学 )

  • 修士(理学) ( 1991年3月   名古屋大学 )

  • 学士(理学) ( 1989年3月   北海道大学 )

研究分野

  • ライフサイエンス / 神経科学一般

  • ライフサイエンス / 病態神経科学

  • ライフサイエンス / 薬理学

経歴(researchmap)

  • 新潟大学   地域創生推進機構   クリエイティブマネージャー   特任教授

    2022年4月 - 現在

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    国名:日本国

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  • 第一三共RDノバーレ株式会社   研究推進部   主幹

    2018年4月 - 2022年3月

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    国名:日本国

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  • 大阪大学   大学院医学系研究科   特任研究員

    2011年4月 - 2014年4月

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    国名:日本国

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  • アスビオファーマ株式会社(株式会社第一サントリー生物医学研究所)   主任研究員

    2005年4月 - 2018年3月

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    国名:日本国

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  • 国立研究開発法人国立精神・神経医療研究センター   神経研究所   客員研究員

    2003年4月 - 2005年3月

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    国名:日本国

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  • 株式会社サントリー生物医学研究所   主任研究員

    2001年1月 - 2003年3月

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    国名:日本国

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  • 国立研究開発法人国立循環器病研究センター内 BF研究所   研究員

    1997年4月 - 2001年3月

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    国名:日本国

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  • サントリー株式会社   生物医学研究所   研究員

    1991年4月 - 1997年3月

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    国名:日本国

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経歴

  • 新潟大学   地域創生推進機構   特任教授

    2022年4月 - 現在

学歴

  • 東京大学   大学院薬学系研究科

    2001年10月 - 2002年7月

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    国名: 日本国

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  • 名古屋大学   大学院理学研究科   生物学専攻

    1989年4月 - 1991年3月

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    国名: 日本国

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  • 北海道大学   理学部   生物学科(動物学専攻)

    1985年4月 - 1989年3月

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    国名: 日本国

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論文

  • Discovery and structure-activity relationships of spiroindolines as novel inducers of oligodendrocyte progenitor cell differentiation. 国際誌

    Katsushi Katayama, Yoshikazu Arai, Kenji Murata, Shoichi Saito, Tsutomu Nagata, Kouhei Takashima, Ayako Yoshida, Makoto Masumura, Shuichi Koda, Hiroyuki Okada, Tsuyoshi Muto

    Bioorganic & medicinal chemistry   28 ( 6 )   115348 - 115348   2020年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A novel series of spiroindoline derivatives was discovered for use as inducers of oligodendrocyte progenitor cell (OPC) differentiation, resulting from optimization of screening hit 1. Exploration of structure-activity relationships led to compound 18, which showed improved potency (rOPC EC50 = 0.0032 μM). Furthermore, oral administration of compound 18 significantly decreased clinical severity in an experimental autoimmune encephalomyelitis (EAE) model.

    DOI: 10.1016/j.bmc.2020.115348

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  • Targeting PTPRZ inhibits stem cell-like properties and tumorigenicity in glioblastoma cells. 国際誌

    Akihiro Fujikawa, Hajime Sugawara, Taisaku Tanaka, Masahito Matsumoto, Kazuya Kuboyama, Ryoko Suzuki, Naomi Tanga, Atsuto Ogata, Makoto Masumura, Masaharu Noda

    Scientific reports   7 ( 1 )   5609 - 5609   2017年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The R5 subfamily of receptor-type protein tyrosine phosphatases (RPTPs) comprises PTPRZ and PTPRG. A recent study on primary human glioblastomas suggested a close association between PTPRZ1 (human PTPRZ) expression and cancer stemness. However, the functional roles of PTPRZ activity in glioma stem cells have remained unclear. In the present study, we found that sphere-forming cells from the rat C6 and human U251 glioblastoma cell lines showed high expression levels of PTPRZ-B, the short receptor isoform of PTPRZ. Stable PTPRZ knockdown altered the expression levels of stem cell transcription factors such as SOX2, OLIG2, and POU3F2 and decreased the sphere-forming abilities of these cells. Suppressive effects on the cancer stem-like properties of the cells were also observed following the knockdown of PTPRG. Here, we identified NAZ2329, a cell-permeable small molecule that allosterically inhibits both PTPRZ and PTPRG. NAZ2329 reduced the expression of SOX2 in C6 and U251 cells and abrogated the sphere-forming abilities of these cells. Tumor growth in the C6 xenograft mouse model was significantly slower with the co-treatment of NAZ2329 with temozolomide, an alkylating agent, than with the individual treatments. These results indicate that pharmacological inhibition of R5 RPTPs is a promising strategy for the treatment of malignant gliomas.

    DOI: 10.1038/s41598-017-05931-8

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  • Small-molecule inhibition of PTPRZ reduces tumor growth in a rat model of glioblastoma. 国際誌

    Akihiro Fujikawa, Asako Nagahira, Hajime Sugawara, Kentaro Ishii, Seiichi Imajo, Masahito Matsumoto, Kazuya Kuboyama, Ryoko Suzuki, Naomi Tanga, Masanori Noda, Susumu Uchiyama, Toshiyuki Tomoo, Atsuto Ogata, Makoto Masumura, Masaharu Noda

    Scientific reports   6   20473 - 20473   2016年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Protein tyrosine phosphatase receptor-type Z (PTPRZ) is aberrantly over-expressed in glioblastoma and a causative factor for its malignancy. However, small molecules that selectively inhibit the catalytic activity of PTPRZ have not been discovered. We herein performed an in vitro screening of a chemical library, and identified SCB4380 as the first potent inhibitor for PTPRZ. The stoichiometric binding of SCB4380 to the catalytic pocket was demonstrated by biochemical and mass spectrometric analyses. We determined the crystal structure of the catalytic domain of PTPRZ, and the structural basis of the binding of SCB4380 elucidated by a molecular docking method was validated by site-directed mutagenesis studies. The intracellular delivery of SCB4380 by liposome carriers inhibited PTPRZ activity in C6 glioblastoma cells, and thereby suppressed their migration and proliferation in vitro and tumor growth in a rat allograft model. Therefore, selective inhibition of PTPRZ represents a promising approach for glioma therapy.

    DOI: 10.1038/srep20473

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  • Protein tyrosine phosphatase receptor type z negatively regulates oligodendrocyte differentiation and myelination. 国際誌

    Kazuya Kuboyama, Akihiro Fujikawa, Makoto Masumura, Ryoko Suzuki, Masahito Matsumoto, Masaharu Noda

    PloS one   7 ( 11 )   e48797   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Fyn tyrosine kinase-mediated down-regulation of Rho activity through activation of p190RhoGAP is crucial for oligodendrocyte differentiation and myelination. Therefore, the loss of function of its counterpart protein tyrosine phosphatase (PTP) may enhance myelination during development and remyelination in demyelinating diseases. To test this hypothesis, we investigated whether Ptprz, a receptor-like PTP (RPTP) expressed abuntantly in oligodendrocyte lineage cells, is involved in this process, because we recently revealed that p190RhoGAP is a physiological substrate for Ptprz. METHODOLOGY/PRINCIPAL FINDINGS: We found an early onset of the expression of myelin basic protein (MBP), a major protein of the myelin sheath, and early initiation of myelination in vivo during development of the Ptprz-deficient mouse, as compared with the wild-type. In addition, oligodendrocytes appeared earlier in primary cultures from Ptprz-deficient mice than wild-type mice. Furthermore, adult Ptprz-deficient mice were less susceptible to experimental autoimmune encephalomyelitis (EAE) induced by active immunization with myelin/oligodendrocyte glycoprotein (MOG) peptide than were wild-type mice. After EAE was induced, the tyrosine phosphorylation of p190RhoGAP increased significantly, and the EAE-induced loss of MBP was markedly suppressed in the white matter of the spinal cord in Ptprz-deficient mice. Here, the number of T-cells and macrophages/microglia infiltrating into the spinal cord did not differ between the two genotypes after MOG immunization. All these findings strongly support the validity of our hypothesis. CONCLUSIONS/SIGNIFICANCE: Ptprz plays a negative role in oligodendrocyte differentiation in early central nervous system (CNS) development and remyelination in demyelinating CNS diseases, through the dephosphorylation of substrates such as p190RhoGAP.

    DOI: 10.1371/journal.pone.0048797

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  • Synthetic glycolipid OCH prevents insulitis and diabetes in NOD mice. 国際誌

    Miho Mizuno, Makoto Masumura, Chiharu Tomi, Asako Chiba, Shinji Oki, Takashi Yamamura, Sachiko Miyake

    Journal of autoimmunity   23 ( 4 )   293 - 300   2004年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Non-obese diabetic (NOD) mice develop diabetes mediated by pathogenic T-helper type 1 (Th1) cells. V alpha 14 Natural killer (NKT) cells are a unique lymphocyte subtype implicated in the regulation of autoimmunity and a good source of protective Th2 cytokines. We recently developed a Th2-skewing NKT cell ligand, OCH. OCH, a sphingosine truncated derivative of alpha-galactosylceramide (alpha-GC), stimulates NKT cells to selectively produce Th2 cytokines. Here we show that OCH prevented the development of diabetes and insulitis in NOD mice. The suppression of insulitis by OCH was more profound compared to alpha-GC. Infiltration of T cells, B cells and macrophages into islets is inhibited in OCH-treated NOD mice. OCH-mediated suppression of diabetes is associated with Th2 bias of anti-islet antigen response and increased IL-10 producing cells among islet-infiltrating leukocytes. Considering the non-polymorphic and well conserved features of the CD1d molecule in mice and humans, these findings not only support the proposed role of NKT cells in the regulation of self-tolerance but also highlight the potential use of OCH for therapeutic intervention in type I diabetes.

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  • Recent Advances in Adenovirus-mediated Gene Therapy for Cerebral Ischemia

    Makoto Masumura, Ryuji Hata

    Current Gene Therapy   3 ( 1 )   43 - 48   2003年2月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Bentham Science Publishers Ltd.  

    DOI: 10.2174/1566523033347516

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  • Characterizing CGI-94 (comparative gene identification-94) which is down-regulated in the hippocampus of early stage Alzheimer's disease brain. 国際誌

    Klaus Heese, Takahiro Nakayama, Ryuji Hata, Makoto Masumura, Hiroyasu Akatsu, Feng Li, Yasuo Nagai, Takayuki Yamamoto, Kenji Kosaka, Takahiro Suemoto, Tohru Sawada

    The European journal of neuroscience   15 ( 1 )   79 - 86   2002年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The treatment of Alzheimer's disease (AD) remains a major challenge because of the incomplete understanding of the triggering events that lead to the selective neurodegeneration characteristic of AD brains. Here we describe a new protein, CGI-94, that is down-regulated at the mRNA level in the hippocampus of early stage AD brain. Transfection experiments with CGI-94 as a green fluorescent protein (GFP)-fusion-protein show that this protein is translocated into the nucleus of the cell. The finding that this protein, which has a bipartite nuclear localization signal, is also observed in the cytoplasm and extracellular space points to a multifunctional protein. Immunohistochemical analyses reveal that CGI-94 is mainly expressed in neurons of the hippocampal formation and the cortex but not in the cerebellar nucleus. In conclusion, the expression of the nucleolar phosphoprotein CGI-94 appears to be disturbed in early processes of neuronal degeneration.

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  • In Vivo Gene Transfer to Cerebral White Matter Lesions with a Recombinant Adenovirus Vector

    Makoto Masumura, Ryuji Hata, Taichi Uetsuki, Isao Nishimura, Yasuo Nagai, Tohru Sawada

    Biochemical and Biophysical Research Communications   287 ( 2 )   440 - 444   2001年9月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1006/bbrc.2001.5609

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  • Up-Regulation of Calcineurin Aβ mRNA in the Alzheimer's Disease Brain: Assessment by cDNA Microarray

    Ryuji Hata, Makoto Masumura, Hiroyasu Akatsu, Feng Li, Hiroko Fujita, Yasuo Nagai, Takayuki Yamamoto, Hidechika Okada, Kenji Kosaka, Masahiro Sakanaka, Tohru Sawada

    Biochemical and Biophysical Research Communications   284 ( 2 )   310 - 316   2001年6月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1006/bbrc.2001.4968

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  • Oligodendroglial cell death with DNA fragmentation in the white matter under chronic cerebral hypoperfusion : comparison between normotensive and spontaneously hypertensive rats

    MASUMURA Makoto, HATA Ryuji, NAGAI Yasuo, SAWADA Tohru

    Neuroscience research : the official journal of the Japan Neuroscience Society   39 ( 4 )   401 - 412   2001年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/s0168-0102(01)00195-x

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  • Increasing in situ nick end labeling of oligodendrocytes in white matter of patients with Binswanger's disease

    Makoto Masumura, Ryuji Hata, Hiroyasu Akatsu, Kenji Kosaka, Takayuki Yamamoto, Yasuo Nagai, Tohru Sawada

    Journal of Stroke and Cerebrovascular Diseases   10 ( 2 )   55 - 62   2001年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:W.B. Saunders  

    Increasing evidence suggests the presence of apoptotic cell death in many neuro-degenerative diseases. However, in Binswanger's disease (BD), no information is available concerning the apoptosis-related pathologic changes that may occur in the white matter. To investigate whether apoptotic cell death is included in the pathophysiology of the white matter changes in BD, autopsied brains from patients with BD (n = 5) were compared with those of non-neurologic controls (n = 5). Terminal deoxynucleotidyl transferase-mediated dUTP in situ nick end labeling (TUNEL) was used as a marker for cell damage with DNA fragmentation. A proteolipid protein (PLP) messenger RNA (mRNA) hybridization signal was also used as a sensitive and specific marker of oligodendrocytes as well as glial fibrillary acidic protein (GFAP) immunoreactivity as a marker of astrocytes. There were frequent TUNEL-positive cells in the rarefied white matter of patients with BD. TUNEL-positive cells were found 15-fold more numerously in BD than in controls (P &lt
    .01). TUNEL-positive cells were presumably oligodendrocytes because of their coexpression with PLP mRNA. The numbers of GFAP-positive astrocytes were significantly decreased in BD compared with those in control subjects. The reduction in numbers of PLP mRNA-positive oligodendrocytes were also seen in BD, but these changes did not reach the level of significance. The pathologic alterations in BD brains include increased TUNEL-positive oligodendrocytes, associated with degradation of myelin. Although TUNEL-positive glial cells did not show typical apoptotic morphologic features, these findings suggest that increase in in situ nick end labeling of oligodendrocytes in white matter may play an important role in the pathophysiology of BD. © 2001 by National Stroke Association.

    DOI: 10.1053/jscd.2001.24660

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  • Caspase-3 activation and inflammatory responses in rat hippocampus inoculated with a recombinant adenovirus expressing the Alzheimer amyloid precursor protein

    Makoto Masumura, Ryuji Hata, Isao Nishimura, Taichi Uetsuki, Tohru Sawada, Kazuaki Yoshikawa

    Molecular Brain Research   80 ( 2 )   219 - 227   2000年9月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/s0169-328x(00)00163-7

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  • Glucose Stimulates the Release of Bombyxin, an Insulin-Related Peptide of the Silkworm Bombyx mori

    Makoto Masumura, Shin'Ichiro Satake, Hironao Saegusa, Akira Mizoguchi

    General and Comparative Endocrinology   118 ( 3 )   393 - 399   2000年6月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1006/gcen.1999.7438

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  • Altered expression of amyloid precursor proteins after traumatic brain injury in rats: In situ hybridization and immunohistochemical study

    Makoto Masumura, Ryuji Hata, Hiroshi Uramoto, Norihito Murayama, Tomochika Ohno, Tohru Sawada

    Journal of Neurotrauma   17 ( 2 )   123 - 134   2000年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Mary Ann Liebert Inc.  

    The expression of alternatively spliced mRNAs for amyloid precursor protein (APP) isoforms and their translation products were examined in the rat cerebral cortex 1, 3, 6, and 12 h and 1, 3, and 7 days (n = 4-5 in each group) after fluid-percussion brain injury. In situ hybridization studies demonstrated that the expression of APP695 mRNA decreased in and around the damaged area of the cerebral cortex exposed to fluid-percussion injury 1 h after the insult. On the other hand, APP751/770 mRNAs were increased in the regions surrounding the damaged cortical areas 1 day after the injury. An increase of immunoreactive APP was detected in the regions around the damaged cortical areas 3 h after traumatic injury and maintained for the following 3 days. The APP immunoreactivity in the damaged cortices declined to the level of sham-operated animals by post-experimental day 7. Using an anti-amyloid β (Aβ) protein (17-24) antibody, no deposits of immunoreactive Aβ (17-24) were observed in any of the samples examined in these experiments. These results suggest that the induction of Kunitz-type protease inhibitor (KPI) domain-containing APP mRNAs and the increased accumulation of APP are involved in the physiological and neuropathological responses of brains under various neurodegenerative conditions, including head trauma.

    DOI: 10.1089/neu.2000.17.123

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  • Bombyxin, an insulin-related peptide of insects, reduces the major storage carbohydrates in the silkworm Bombyx mori

    Shin'Ichiro Satake, Makoto Masumura, Hironori Ishizaki, Koji Nagata, Hiroshi Kataoka, Akinori Suzuki, Akira Mizoguchi

    Comparative Biochemistry and Physiology - B Biochemistry and Molecular Biology   118 ( 2 )   349 - 357   1997年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The effects of an insect insulin-related peptide, bombyxin, on carbohydrate metabolism were investigated in the silkworm Bombyx mori. Bombyxin lowered the concentration of the major hemolymph sugar, trehalose, in a dose-dependent manner when injected into neck-ligated larvae. Bombyxin also caused elevated trehalase activity in the midgut and muscle, suggesting that bombyxin induces hypotrehalosemia by promoting the hydrolysis of hemolymph trehalose to glucose anti thereby facilitating its transport into tissues. In addition, bombyxin reduced the glycogen content in the fat body and concurrently raised the percentage of active glycogen phosphorylase in this tissue. Because hemolymph trehalose is also a major storage form of carbohydrate in insects, our results indicate that bombyxin reduces the amount of both principal storage carbohydrates in B. mori larvae. It is therefore suggested that although bombyxin is involved in the control of carbohydrate metabolism like insulin, the physiological role of bombyxin in insects is different from that of insulin in mammals.

    DOI: 10.1016/S0305-0491(97)00166-1

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  • Selective induction of fibroblast growth factor receptor-1 mRNA after transient focal ischemia in the cerebral cortex of rats

    Makoto Masumura, Norihito Murayama, Teruyoshi Inoue, Tomochika Ohno

    Neuroscience Letters   213 ( 2 )   119 - 122   1996年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier Ireland Ltd  

    The expression of the mRNA of four members of the fibroblast growth factor (FGF) receptor family, was examined in rats subjected to temporal middle cerebral artery occlusion using an in situ hybridization technique. Fibroblast growth factor receptor-1 (FGFR-1) mRNA was strongly expressed in neurons of the cerebral cortex, whereas mRNAs of the other 3 subtypes of FGFRs (FGFR-2, -3, and -4) were not expressed. After temporal occlusion of the middle cerebral artery, expression of FGFR-1 mRNA in cerebral cortical neurons markedly increased in association with the progressive neuronal death
    this increase was evident for at least 5 days after the focal ischemia. In view of the neuroprotective activity of basic FGF reported so far, the present results suggest that FGFR-1 induction may subserve to self-protect neurons in the ischemic penumbral field of the cerebral cortex.

    DOI: 10.1016/0304-3940(96)12841-X

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MISC

  • 再発寛解型多発性硬化症における微小脳血管膜蛋白に対する標的抗原分子の同定法の確立

    竹下幸男, 藤川晋, 牧野智宏, 星野将人, 花田雄志, 升村誠, 西原秀昭, 西原秀昭, 清水文崇, 古賀道明, 神田隆

    Neuroimmunology   23 ( 1 )   2018年

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  • 再発・寛解型マウス多発性硬化症モデルにおける再発には血管新生を伴った炎症細胞の浸潤が関与している

    佐々木千恵, 板東良雄, 升村誠, 中村隆一, 幸田修一, 喜田成孝

    日本解剖学会総会・全国学術集会講演プログラム・抄録集   122nd   2017年

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  • 再発・寛解型マウス多発性硬化症モデルにおける脱髄の形態学的解析

    板東良雄, 佐々木千恵, 升村誠, 中村隆一, 幸田修一, 吉田成孝

    日本生物学的精神医学会(Web)   38th   2016年

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  • 再発・寛解型マウス多発性硬化症モデルにおける脱髄の形態学的解析

    佐々木千恵, 板東良雄, 升村誠, 中村隆一, 幸田修一, 暮地本宙己, 渡部剛, 吉田成孝

    日本解剖学会総会・全国学術集会講演プログラム・抄録集   121st   2016年

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  • Ptprz欠損マウスは実験的自己免疫性脳脊髄炎に抵抗性である

    久保山和哉, 藤川顕寛, 升村誠, 鈴木亮子, 松本匡史, 野田昌晴

    日本生化学会大会(Web)   85th   2012年

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  • 自己免疫疾患におけるTh1/Th2免疫バランスを是正する新規糖脂質誘導体の創製

    村田健司, 鳥羽哲也, 中西恭子, 高橋美徳, 竹本尚弘, 赤羽美奈子, 升村誠, 山村隆, 三宅幸子, 案浦洋一

    メディシナルケミストリーシンポジウム講演要旨集   24th   2005年

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  • NKT細胞合成糖脂質リガンドOCHによるNODマウスにおける糖尿病発症の抑制

    三宅幸子, 千葉麻子, 山村隆, 升村誠, 水野美歩

    日本免疫学会総会・学術集会記録   33   2003年

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  • アルツハイマー病初期患者の海馬における遺伝子発現変化 Microarrayによる検討

    秦龍二, 升村誠, 赤津裕康, 山本孝之, 阪中雅広, 小阪憲司, 沢田徹

    臨床神経学   41 ( 11 )   2001年

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  • Binswanger病患者大脳白質におけるTUNEL陽性細胞

    升村誠, 秦龍二, 永井康雄, 沢田徹

    脳循環代謝   13 ( 2 )   2001年

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  • 組換えアデノウイルスを用いたラット脳内APP遺伝子導入によるガスパーゼ3活性化と炎症反応誘導

    升村誠, 秦龍二, 西村伊三男, 植月太一, 沢田徹, 吉川和明

    神経化学   39 ( 3 )   2000年

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  • Binswanger病患者大脳白質におけるTUNEL陽性細胞

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