Details of a Researcher - Moriwaki, Yasuhiro

Moriwaki, Yasuhiro

写真a

Affiliation: Faculty of Pharmacy, Department of Pharmacy 薬学教育研究センター (Shiba-Kyoritsu)

Position: Assistant Professor/Senior Assistant Professor

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Career 【 Display / hide 】

2002.04

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2003.03

大阪府立成人病センター研究所, 日本学術振興会特別研究員
2003.04

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2003.08

理化学研究所　脳科学総合研究センター, 日本学術振興会特別研究員
2003.09

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2005.03

理化学研究所　脳科学総合研究センター, 研究員
2005.04

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2007.03

共立薬科大学, 助手
2007.04

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2008.03

共立薬科大学, 助教

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Academic Background 【 Display / hide 】

2000.04

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2003.03

Nara Institute of Science and Technology, Graduate School, Division of Biological Science

Graduate School, Completed, Doctoral course

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Academic Degrees 【 Display / hide 】

博士（バイオサイエンス）, 奈良先端科学技術大学院大学, Coursework, 2003.03

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Licenses and Qualifications 【 Display / hide 】

第一種放射線取扱主任者（選任）, 2022.04

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Papers 【 Display / hide 】

IgG-Binding Peptidomimetic Mixed-Charge Polymer-Modified Resins for Chromatographic Purification of Antibodies.

Deura K, Sakama A, Moriwaki Y, Citterio D, Hiruta Y.

ACS Appl Mater Interfaces. (American Chemical Society (United States)) 2024.11

Research paper (scientific journal), Joint Work, Accepted, ISSN 19448244

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The process of antibody purification using Fc affinity ligands such as protein A, G, and L faces several challenges including high cost, low stability, and loss of antibody activity due to harsh elution conditions. Here, we describe a chromatographic purification of antibodies utilizing a pH-responsive mixed-charge polymer that mimics the IgG-binding peptide (Z34C) derived from the B domain of protein A. The protein A mimetic resins were prepared by modifying the surface of a TOYOPEARL, methacrylate resin with a polymer that mimics the amino acid sequence of Z34C and the functions of histidine and acidic and neutral amino acids using histamine methacrylamide (HisMA), methacrylic acid, and neutral monomers. The therapeutic monoclonal antibody (mAb), rituximab, was retained on the column at pH 7 and eluted under mildly acidic conditions at pH 5 using a protein A mimetic resin (HisMA20-EEMA) optimized for antibody interaction. The injected antibodies were selectively captured on the column by hydrophobic and electrostatic interactions with the protein A mimetic polymer under neutral conditions and eluted by electrostatic repulsion under acidic conditions. The HisMA20-EEMA column successfully purified mAbs from mixtures with BSA, mouse ascites fluid, and hybridoma cell culture supernatant. In addition, the HisMA20-EEMA column consistently achieved 90% antibody recovery in 100 consecutive purifications from cell culture supernatant. The antibody purification method presented in this study is low cost, highly durable, easy to synthesize, and allows for mild elution conditions. The results demonstrate that the approach of mimicking IgG-binding peptides with mixed-charge polymers is useful for the development of column packing materials for antibody purification.
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Suppression of Neuroinflammation by Coffee Component Pyrocatechol via Inhibition of NF-κB in Microglia

Murata T, Tago K, Miyata K, Moriwaki Y, Misawa H, Kobata K, Nakazawa Y, Tamura H, Funakoshi-Tago M.

International Journal of Molecular Sciences (International Journal of Molecular Sciences) 25 ( 1 ) 2023.12

Research paper (scientific journal), Joint Work, Accepted, ISSN 16616596

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According to numerous studies, it has been epidemiologically suggested that habitual coffee intake seems to prevent the onset of neurodegenerative diseases. In this study, we hypothesized that coffee consumption suppresses neuroinflammation, which is closely related to the development of neurodegenerative diseases. Using microglial BV-2 cells, we first found that the inflammatory responses induced by lipopolysaccharide (LPS) stimulation was diminished by both coffee and decaffeinated coffee through the inhibition of an inflammation-related transcription factor, nuclear factor-κB (NF-κB). Pyrocatechol, a component of roasted coffee produced by the thermal decomposition of chlorogenic acid, also exhibited anti-inflammatory activity by inhibiting the LPS-induced activation of NF-κB. Finally, in an inflammation model using mice injected with LPS into the cerebrum, we observed that intake of pyrocatechol as well as coffee decoctions drastically suppressed the accumulation of microglia and the expression of interleukin-6 (IL-6), tumor necrosis factor α (TNFα), CCL2, and CXCL1 in the inflammatory brain. These observations strongly encourage us to hypothesize that the anti-inflammatory activity of pyrocatechol as well as coffee decoction would be useful for the suppression of neurodegeneration and the prevention of the onsets of Alzheimer’s (AD) and Perkinson’s diseases (PD).
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GTS-21 Enhances Regulatory T Cell Development from T Cell Receptor-Activated Human CD4<sup>+</sup> T Cells Exhibiting Varied Levels of CHRNA7 and CHRFAM7A Expression

Mashimo M., Fujii T., Ono S., Moriwaki Y., Misawa H., Azami T., Kasahara T., Kawashima K.

International Journal of Molecular Sciences (International Journal of Molecular Sciences) 24 ( 15 ) 2023.07

Research paper (scientific journal), Accepted, ISSN 16616596

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Immune cells such as T cells and macrophages express α7 nicotinic acetylcholine receptors (α7 nAChRs), which contribute to the regulation of immune and inflammatory responses. Earlier findings suggest α7 nAChR activation promotes the development of regulatory T cells (Tregs) in mice. Using human CD4+ T cells, we investigated the mRNA expression of the α7 subunit and the human-specific dupα7 nAChR subunit, which functions as a dominant-negative regulator of ion channel function, under resting conditions and T cell receptor (TCR)-activation. We then explored the effects of the selective α7 nAChR agonist GTS-21 on proliferation of TCR-activated T cells and Treg development. Varied levels of mRNA for both the α7 and dupα7 nAChR subunits were detected in resting human CD4+ T cells. mRNA expression of the α7 nAChR subunit was profoundly suppressed on days 4 and 7 of TCR-activation as compared to day 1, whereas mRNA expression of the dupα7 nAChR subunit remained nearly constant. GTS-21 did not alter CD4+ T cell proliferation but significantly promoted Treg development. These results suggest the potential ex vivo utility of GTS-21 for preparing Tregs for adoptive immunotherapy, even with high expression of the dupα7 subunit.
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Regulation of immune functions by non-neuronal acetylcholine (ACh) via muscarinic and nicotinic ACh receptors.

Mashimo M, Moriwaki Y, Misawa H, Kawashima K, Fujii T.

International Journal of Molecular Sciences (MDPI) 22 ( 13 ) 6818 2021.06

Research paper (scientific journal), Joint Work, Accepted, ISSN 16616596

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Acetylcholine (ACh) is the classical neurotransmitter in the cholinergic nervous system. However, ACh is now known to regulate various immune cell functions. In fact, T cells, B cells, and macrophages all express components of the cholinergic system, including ACh, muscarinic, and nicotinic ACh receptors (mAChRs and nAChRs), choline acetyltransferase, acetylcholinesterase, and choline transporters. In this review, we will discuss the actions of ACh in the immune system. We will first briefly describe the mechanisms by which ACh is stored in and released from immune cells. We will then address Ca2+ signaling pathways activated via mAChRs and nAChRs on T cells and B cells, highlighting the importance of ACh for the function of T cells, B cells, and macrophages, as well as its impact on innate and acquired (cellular and humoral) immunity. Lastly, we will discuss the effects of two peptide ligands, secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related peptide-1 (SLURP-1) and hippocampal cholinergic neurostimulating peptide (HCNP), on cholinergic activity in T cells. Overall, we stress the fact that ACh does not function only as a neurotransmitter; it impacts immunity by exerting diverse effects on immune cells via mAChRs and nAChRs.
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New pathways for the skin´s stress response: the cholinergic neuropeptide SLURP-1 can activate mast cells and alter cytokine production in mice.

Ertle CM, Rommel FR, Tumala S, Moriwaki Y, Klein J, Kruse J, Gieler U, Peters EMJ.

Frontiers in Immunology (Frontiers in Immunology) 12 631881 2021.03

Research paper (scientific journal), Joint Work, Accepted

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Background: The alpha7 nicotinic acetylcholine receptor (Chrna7) plays an essential anti-inflammatory role in immune homeostasis and was recently found on mast cells (MC). Psychosocial stress can trigger MC hyperactivation and increases pro-inflammatory cytokines in target tissues such as the skin. If the cholinergic system (CS) and Chrna7 ligands play a role in these cascades is largely unknown. Objective: To elucidate the role of the CS in the response to psychosocial stress using a mouse-model for stress-triggered cutaneous inflammatory circuits. Methods: Key CS markers (ACh, Ch, SLURP-1, SLURP-2, Lynx1, Chrm3, Chrna7, Chrna9, ChAT, VAChT, Oct3, AChE, and BChE) in skin and its MC (sMC), MC activation, immune parameters (TNFα, IL1β, IL10, TGFβ, HIF1α, and STAT3) and oxidative stress were analyzed in skin from 24 h noise-stressed mice and in cultured MC (cMC) from C57BL/6 or Chrna7-Knockout mice. Results: First, Chrna7 and SLURP-1 mRNA were exclusively upregulated in stressed skin. Second, histomorphometry located Chrna7 and SLURP-1 in nerves and sMC and demonstrated upregulated contacts and increased Chrna7+ sMC in stressed skin, while 5 ng/mL SLURP-1 degranulated cMC. Third, IL1β+ sMC were high in stressed skin, and while SLURP-1 alone had no significant effect on cMC cytokines, it upregulated IL1β in cMC from Chrna7-KO and in IL1β-treated wildtype cMC. In addition, HIF1α+ sMC were high in stressed skin and Chrna7-agonist AR-R 17779 induced ROS in cMC while SLURP-1 upregulated TNFα and IL1β in cMC when HIF1α was blocked. Conclusions: These data infer that the CS plays a role in the regulation of stress-sensitive inflammatory responses but may have a surprising pro-inflammatory effect in healthy skin, driving IL1β expression if SLURP-1 is involved.
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Papers, etc., Registered in KOARA 【 Display / hide 】

Development of a curative treatment for myasthenia gravis using a bispecific antibody drug

Moriwaki, Yasuhiro

科学研究費補助金研究成果報告書 2022
Development of next-generation antibody drugs targeting urothelial carcinoma and myeloma

Moriwaki, Yasuhiro

学事振興資金研究成果実績報告書 (慶應義塾大学) 2022
Development of novel therapeutic strategies for myasthenia gravis.

Moriwaki, Yasuhiro

福澤諭吉記念慶應義塾学事振興基金事業報告集 (福澤基金運営委員会) 2021
Development of novel therapeutic strategies for myasthenia gravis

Moriwaki, Yasuhiro

福澤諭吉記念慶應義塾学事振興基金事業報告集 (福澤基金運営委員会) 2020
Elucidation of the molecular mechanism of HEG1 in controlling proliferation of mesothelioma cell.

Moriwaki, Yasuhiro

学事振興資金研究成果実績報告書 (慶應義塾大学) 2019

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Reviews, Commentaries, etc. 【 Display / hide 】

ニコチン受容体修飾因子SLURP-1による乾癬の新規治療戦略

森脇康博

臨床免疫・アレルギー科 66 ( 1 ) 45 - 49 2016.07

Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media), Single Work
パーキンソン病と小胞体ストレス

森脇康博, 高橋良輔

現代医療 36 ( 4 ) 129 - 134 2004.04

Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media), Joint Work

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Presentations 【 Display / hide 】

ペプチドミメティクス分子設計による抗体精製用合成高分子カラム充填剤の開発

出浦浩一, 坂間亮浩, 森脇康博, チッテリオダニエル, 蛭田勇樹.

日本分析化学会第73年会,

2024.09
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Poster presentation
ニコチン受容体内在性修飾蛋白質Ly6Hの脳内発現部位と生理的機能の解明

森脇康博, 井上直和, 辻祥太郎.

Neuro2024 (福岡) ,

2024.07
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Poster presentation
Antibody purification using synthetic polymer column packing materials with peptidomimetic molecular design

Deura K, Moriwaki Y, Citterio Y, Hiruta Y.

HPLC2024 (Colorad) ,

2024.07
内在性神経毒類似タンパク質によるニコチン受容体の機能変換メカニズムの解明

三澤日出巳, 森﨑祐太, 森脇康博.

第38回令和5年度喫煙科学研究財団助成研究発表会,

2024.07
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Oral presentation (general)
腫瘍マーカータンパク質ファミリー、Ly6 super familyの一つであるLy6Hに対するモノクローナル抗体の作製

森脇康博,井上直和, 辻祥太郎.

第43回日本分子腫瘍マーカー研究会,

2023.09
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Oral presentation (general)

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

革新的バイオセパレーションを実現する機能性高分子修飾ナノ界面の創製

2024.04

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2028.03

文部科学省・日本学術振興会, 基盤研究(B), Coinvestigator(s)
ニコチン受容体機能抑制タンパク質を標的とした認知症治療戦略の構築

2024.04

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2027.03

喫煙科学研究財団, 一般研究, No Setting, Principal investigator
尿路上皮癌を標的としたバイパラトピック抗体医薬品の開発

2024.04

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2025.03

慶應義塾学事振興資金, 個人研究特B, No Setting, Principal investigator
次世代抗体医薬品の開発を加速するRI標識に関する基盤技術開発とRI標識抗体医薬の実用化研究

2023.04

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Present

国立研究開発法人日本医療研究開発機構(AMED), 次世代治療・診断実現のための創薬基盤技術開発事業, Coinvestigator(s)
Physiological and pathological roles of functional inhibitors of memory-related nicotinic receptors on memory.

2023.04

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2026.03

文部科学省・日本学術振興会, 基盤研究(C), Principal investigator

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Awards 【 Display / hide 】

HPLC2024, Best Poster Award

Deura K, Moriwaki Y, Citterio Y, Hiruta Y., 2024.07, HPLC2024, Antibody purification using synthetic polymer column packing materials with peptidomimetic molecular design

Type of Award： Award from international society, conference, symposium, etc., Country： United States
第137回日本薬理学会関東部会　若手優秀発表賞

渡邉みずほ, 森脇康博, 久保那月, 加藤総夫, 三澤日出巳., 2017.10, 内在性神経毒素類似タンパク質Ly6Hによるニコチン受容体調整.

Type of Award： Award from Japanese society, conference, symposium, etc.
第131回日本薬理学会関東部会　若手優秀発表賞

森﨑祐太, 坪田充司, 森脇康博, 山中宏二, 三澤日出巳., 2014.10, 筋萎縮性側索硬化症における運動ニューロン変性とオステオポンチン及びマトリックスメタロプロテアーゼ-9の関連の検討.

Type of Award： Award from Japanese society, conference, symposium, etc.