Details of a Researcher - Kawahara, Ryota

Kawahara, Ryota

写真a

Affiliation: Faculty of Science and Technology, Department of Applied Chemistry ( Yagami )

Position: Assistant Professor (Non-tenured)/Research Associate (Non-tenured)/Instructor (Non-tenured)

E-mail Address

Related Websites

http://www.applc.keio.ac.jp/~simizu/

External Links

https://orcid.org/0000-0003-2692-2065

Scopus Paper Info

Paper Count: 13 Citation Count: 142 h-index: 7

Click to view the Scopus page. The data was downloaded from Scopus API in July 12, 2026, via http://api.elsevier.com and http://www.scopus.com .

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Profile Summary 【 Display / hide 】

We conduct basic research to elucidate the pathogenesis of diseases and to develop therapeutic drugs. In particular, we focus on "vasculogenic mimicry" and "glycosylation," which are biological phenomena closely related to malignant transformation of cancer, and analyze their mechanisms using chemical approaches.

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Career 【 Display / hide 】

2020.04

-

2022.03

JSPS Research Fellowship for Young Scientists DC2
2022.04

-

2024.03

ノバルティスファーマ株式会社
2024.04

-

Present

Keio University, Department of Applied Chemistry, Faculty of Science and Technology, Research associate

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Academic Background 【 Display / hide 】

2013.04

-

2017.03

Keio University, Faculty of Science and Technology, Department of Applied Chemistry
2017.04

-

2019.03

Keio University, 理工学研究科
2019.04

-

2022.03

Keio University, 理工学研究科

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Academic Degrees 【 Display / hide 】

Ph.D., Keio University, Coursework, 2022.03

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Research Areas 【 Display / hide 】

Life Science / Molecular biology
Life Science / Molecular biology
Life Science / Cell biology
Life Science / Cell biology

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Research Keywords 【 Display / hide 】

がん生物学
がん生物学
ケミカルバイオロジー
ケミカルバイオロジー
糖鎖生物学

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Papers 【 Display / hide 】

Limited involvement of MMP2, MMP9 and MMP14 in vasculogenic mimicry formation of human tumor cell lines

Yoshida T., Fukuoka E., Kawahara R., Matsubara T., Simizu S.

Biochimica Et Biophysica Acta General Subjects 1870 ( 7 ) 2026.07

ISSN 03044165

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Vasculogenic mimicry (VM) is a phenomenon in which tumor cells form capillary-like networks without endothelial cells and is associated with tumor progression and poor prognosis. Understanding mechanisms of VM and identifying its reliable biomarkers are critical for developing novel therapeutic strategies. Matrix metalloproteinases (MMPs), which degrade extracellular matrix (ECM) components, have been reported to regulate VM. Indeed, increased expression of MMPs has been reported in VM-positive patients; however, their precise roles in VM formation remain unclear. Therefore, in this study, we investigated the roles of MMPs, particularly MMP2, MMP9, and MMP14, in VM formation and assessed their potential as VM markers. Expression levels of MMP2 and MMP9 in multiple types of cancer cell lines did not correlate with VM-forming ability, and knockout of either gene in HT1080 cells had no significant effect on VM formation. In contrast, MMP14 expression showed a positive correlation with VM formation, although VM structures were still maintained in MMP14-knockout MDA-MB-231 cells. Additionally, treatment with GM6001, a broad-spectrum MMPs inhibitor, had no significant impact on VM formation. Moreover, co-treatment with various known anticancer agents and GM6001 did not synergistically suppress VM. These findings suggest that MMPs inhibition does not give a vulnerability in VM formation. Collectively, our results indicate that MMPs, particularly MMP2, MMP9, and MMP14, are unlikely to play critical roles in VM formation.
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Total Synthesis of Keramaphidin B and Ingenamine

Kurihara Y., Yagi M., Yoshimura S., Ito K., Shimotani Y., Uematsu M., Noguchi T., Yasufuku H., Okita A., Fukaya K., Oishi T., Kawahara R., Simizu S., Chida N., Okamura T., Sato T.

Synthesis Germany (Georg Thieme Verlag KG) 58 ( 8 ) 873 - 888 2026

ISSN 00397881

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The full details of the total synthesis of keramaphidin B and ingenamine are reported herein. The most conspicuous transformation in our total synthesis is the base-catalyzed Diels-Alder reaction using dynamic regioselective crystallization (alternatively referred to as crystallization-induced transformation). The tertiary alcohol, which is used for the base-catalyzed activation in the Diels-Alder reaction, is removed as its p-fluorobenzoate using SmI 2 (HMPA) 4. Double macrocyclic alkylation enables the regioselective construction of two macrocycles in a single step. The developed sequence is highly efficient, achieving the unified total synthesis of keramaphidin B and ingenamine within 13 steps from commercially available compounds. Our biological study elucidated the significant role of the two macrocycles in their antiproliferative effects against human cancer cell lines.
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C-mannosylation promotes ADAMTS1 activation and secretion in human testicular germ cell tumor NEC8 cells

Kobayashi T., Suzuki T., Kawahara R., Harai N., Dohmae N., Simizu S.

FEBS Letters 599 ( 21 ) 3113 - 3123 2025.11

ISSN 00145793

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C-mannosylation is a protein glycosylation that regulates the functions of target proteins. Although it has been reported that a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1), an important spermatogenesis factor, is C-mannosylated, the roles of C-mannosylation in ADAMTS1 in testicular cells are still unclear. In this study, we found that ADAMTS1 is C-mannosylated at Trp<sup>562</sup> and Trp<sup>565</sup> in testis germ NEC8 cells. To determine the roles of C-mannosylation in ADAMTS1, we established cells expressing a C-mannosylation-defective ADAMTS1, in which C-mannosylated tryptophan residues were replaced with phenylalanine residues (ADAMTS1/2WF). Processing and secretion of ADAMTS1/2WF were both inhibited compared to those of wild-type. Moreover, wild-type ADAMTS1 degraded aggrecan, whereas ADAMTS1/2WF could not. These results indicate the impact of C-mannosylation on ADAMTS1 function.
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Total Synthesis of Isodaphlongamine H by Iridium-Catalyzed Reductive [3 + 2] Cycloaddition of N-Hydroxylactam

Iwamoto S., Nakano R., Sasaki K., Kobayashi S., Taira Y., Takei K., Kawakita R., Tokuyama A., Nakamura H., Tomoike M., Kawahara R., Murase A., Simizu S., Chida N., Okamura T., Sato T.

Angewandte Chemie International Edition 64 ( 29 ) 2025

ISSN 14337851

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The total synthesis of isodaphlongamine H based on a lactam strategy, which enables quick access to complex cyclic amines, is described. The strategy begins with alkylation of a chiral lactam and subsequent N-oxidation via an imino ether to afford the N-hydroxylactam. For the key transformation to functionalize the amide carbonyl, an iridium-catalyzed reductive [3 + 2] cycloaddition of the N-hydroxylactam provides a tricyclic isoxazolidine in a one-pot process. After the coupling reaction with an allylic silane fragment, the total synthesis is accomplished through intramolecular Hosomi–Sakurai allylation to construct a pentacyclic core. The deoxygenated pentacyclic intermediate shows higher cytotoxicity against HeLa and U937 cell lines than isodaphlongamine H, and might become a lead compound for further biological study.
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Identification of C-mannosylation in a receptor tyrosine kinase AXL

Mori K., Suzuki T., Waki U., Hayashi S., Kadono S., Kawahara R., Takeuchi M., Mizuta H., Dohmae N., Katayama R., Simizu S.

Glycobiology 34 ( 11 ) 2024.11

ISSN 09596658

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C-mannosylation is a unique type of glycosylation in which a mannose is added to tryptophan in a protein. However, the biological function of C-mannosylation is still largely unknown. AXL is a receptor tyrosine kinase, and its overexpression contributes to tumor malignancy. The role of AXL in cancer cells is broad, including invasion, drug resistance, and vasculogenic mimicry formation. Although Trp320 of AXL was predicted to be C-mannosylated, it has not been confirmed. Here, we demonstrated that Trp320 of AXL is C-mannosylated, measured by mass spectrometry of recombinant AXL purified from various cancer cells. Furthermore, re-expression of C-mannosylation-deficient AXL in human breast cancer MDA-MB-231 cells lacking AXL by the CRISPR/Cas9 system resulted in reduction of vasculogenic mimicry formation. Interestingly, phosphorylation levels of AKT in C-mannosylation-deficient AXL re-expressing cells were comparable to those of parental and wild-type AXL re-expressing cells. These results represent the first discovery of C-mannosylation in a receptor tyrosine kinase and the possibility that C-mannosylation may affect AXL function, distinct from its downstream signaling in cancer cells.
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Papers, etc., Registered in KOARA 【 Display / hide 】

Analysis of cell surface receptors in vasculogenic mimicry of human cancer cells

Kawahara, Ryōta

(慶應義塾大学大学院理工学研究科) 2021
Analysis of cell surface receptors in vasculogenic mimicry of human cancer cells

Kawahara, Ryōta

(慶應義塾大学大学院理工学研究科) 2021
Analysis of cell surface receptors in vasculogenic mimicry of human cancer cells

Kawahara, Ryōta

(慶應義塾大学大学院理工学研究科) 2021

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

がん細胞の血管擬態におけるマーカータンパク質の同定

2020.04

-

2022.03

Grants-in-Aid for Scientific Research, 川原遼太, Grant-in-Aid for JSPS Fellows, No Setting

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本研究の概要は、がん悪性化に寄与する血管擬態について、その存在や進行度の指標となるマーカータンパク質を同定することである。血管擬態とは、がん細胞自身が血管のように擬態することで腫瘍内血管を作り出し、腫瘍成長のエネルギー源となる血液の循環を促す現象である。そのため、血管擬態形成時に特異的に発現するタンパク質を同定し、それをバイオマーカーとして応用できれば、がんの予後診断や治療法選択を改善させられることが期待できる。本研究では、培養細胞を用いた実験により血管擬態のマーカータンパク質を同定することを目指す。
がん細胞の血管擬態におけるマーカータンパク質を探索するため、3つの遺伝子に焦点を当て、それらが血管擬態形成を制御し得るか否かを調べた。
ErbB4は、がん遺伝子として有名なEGFRやHER2と同じファミリーに属する遺伝子である。しかし、ErbB4とがんの関係については明確でないのが現状である。そこで、ヒト乳がん細胞株を用いて解析を行った結果、ErbB4が血管擬態形成を抑制することが明らかになった。一方で、リガンド刺激や遺伝子変異によりErbB4を活性化させると、血管擬態形成を促進させることが示された。さらに、EGFR阻害剤として知られているアファチニブを細胞に処理することで、ErbB4を介した血管擬態形成が効果的に抑制できることを示した。これらの結果により、ErbB4は血管擬態を正負に調節することでがんの進行に関与することが明らかになった。
MetAP2は血管新生に寄与する遺伝子として知られているが、血管擬態における役割は分かっていない。そこで、阻害剤処理や遺伝子ノックアウトにより解析した結果、MetAP2の阻害によりヒトがん細胞の血管擬態が著しく抑制されることが明らかになった。
Tyrosinaseはメラニン産生において必要不可欠な酵素であるが、メラノーマにおける役割はほとんど分かっていない。そこで、メラノーマ細胞においてtyrosinase遺伝子を欠損させた結果、血管擬態形成が促進した。また、色素欠乏症で報告されたアミノ酸変異が、tyrosinaseの血管擬態制御能に影響を与えることを示した。
以上のように、がん細胞の種類によって血管擬態を制御する遺伝子が異なり、各々の遺伝子は血管擬態のマーカーとして有望である可能性が示された。また、これらの遺伝子は既に阻害剤も開発されているため、がんの治療標的としても有望である。
令和3年度が最終年度であるため、記入しない。
令和3年度が最終年度であるため、記入しない。