2024/04/03 更新

写真a

イシイ　トモヒロ
石井　智裕
Ishii Tomohiro
所属
先端医学研究所 病態解析学部門 助教
職名
助教
プロフィール
血管は，通常時ではその構造をほとんど変えないが，傷害などをうけると，組織再生のために血管新生が誘導され，損傷部へ向かって血管内皮細胞が動的変化を起こします．血管新生は，血管内皮細胞の伸長，吻合，出芽，蛇行，退縮などの過程を経て，元の構造に戻る現象ですが，その詳細なメカニズムは明らかとなっていません．我々は，成体ゼブラフィッシュの皮膚創傷を血管新生モデルとし，血管新生における各細胞の動態および分子活性をライブイメージングにより解析し，その分子機構の解明を目指しています．
外部リンク

研究キーワード

  • 再生

  • ゼブラフィッシュ

  • 血管新生

  • ライブイメージング

  • ペリサイト

研究分野

  • ライフサイエンス / 病態医化学  / 血管新生

  • ライフサイエンス / 形態、構造  / 血管新生

学歴

  • 慶應義塾大学   薬学研究科   博士課程

    2013年4月 - 2017年9月

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  • 慶應義塾大学   薬学部   薬学科

    2008年4月 - 2013年3月

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  • 共立薬科大学   薬学部   薬学科

    2007年4月 - 2008年3月

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経歴

  • 日本医科大学   先端医学研究所 病態解析学部門 分子細胞構造学分野   助教

    2020年1月 - 現在

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    国名：日本国

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  • 日本医科大学   先端医学研究所 病態解析学部門 分子細胞構造学分野   博士研究員

    2019年5月 - 2019年12月

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  • 慶應義塾大学   薬学部 薬理学講座   共同研究員

    2018年7月 - 現在

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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 神経薬理研究部   流動研究員

    2018年7月 - 2019年4月

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  • 慶應義塾大学   薬学部 薬理学講座   研究員

    2017年9月 - 2018年6月

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所属学協会

  • 日本血管生物医学会

    2019年8月 - 現在

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  • 日本生理学会

    2023年11月 - 現在

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  • 日本神経科学学会

    2015年2月 - 現在

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論文

  • Endothelial cells regulate alveolar morphogenesis by constructing basement membranes acting as a scaffold for myofibroblasts. 国際誌

    Haruko Watanabe-Takano, Katsuhiro Kato, Eri Oguri-Nakamura, Tomohiro Ishii, Koji Kobayashi, Takahisa Murata, Koichiro Tsujikawa, Takaki Miyata, Yoshiaki Kubota, Yasuyuki Hanada, Koichi Nishiyama, Tetsuro Watabe, Reinhard Fässler, Hirotaka Ishii, Naoki Mochizuki, Shigetomo Fukuhara

    Nature communications   15 ( 1 )   1622 - 1622   2024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）  

    Alveologenesis is a spatially coordinated morphogenetic event, during which alveolar myofibroblasts surround the terminal sacs constructed by epithelial cells and endothelial cells (ECs), then contract to form secondary septa to generate alveoli in the lungs. Recent studies have demonstrated the important role of alveolar ECs in this morphogenetic event. However, the mechanisms underlying EC-mediated alveologenesis remain unknown. Herein, we show that ECs regulate alveologenesis by constructing basement membranes (BMs) acting as a scaffold for myofibroblasts to induce septa formation through activating mechanical signaling. Rap1, a small GTPase of the Ras superfamily, is known to stimulate integrin-mediated cell adhesions. EC-specific Rap1-deficient (Rap1iECKO) mice exhibit impaired septa formation and hypo-alveolarization due to the decreased mechanical signaling in myofibroblasts. In Rap1iECKO mice, ECs fail to stimulate integrin β1 to recruit Collagen type IV (Col-4) into BMs required for myofibroblast-mediated septa formation. Consistently, EC-specific integrin β1-deficient mice show hypo-alveolarization, defective mechanical signaling in myofibroblasts, and disorganized BMs. These data demonstrate that alveolar ECs promote integrin β1-mediated Col-4 recruitment in a Rap1-dependent manner, thereby constructing BMs acting as a scaffold for myofibroblasts to induce mechanical signal-mediated alveologenesis. Thus, this study unveils a mechanism of organ morphogenesis mediated by ECs through intrinsic functions.

    DOI： 10.1038/s41467-024-45910-y

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  • Rap1 small GTPase is essential for maintaining pulmonary endothelial barrier function in mice. 国際誌

    Kiyotake Yamamoto, Haruko Watanabe-Takano, Eri Oguri-Nakamura, Hitomi Matsuno, Daiki Horikami, Tomohiro Ishii, Ryuji Ohashi, Yoshiaki Kubota, Koichi Nishiyama, Takahisa Murata, Naoki Mochizuki, Shigetomo Fukuhara

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology   37 ( 12 )   e23310   2023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）  

    Vascular permeability is dynamically but tightly controlled by vascular endothelial (VE)-cadherin-mediated endothelial cell-cell junctions to maintain homeostasis. Thus, impairments of VE-cadherin-mediated cell adhesions lead to hyperpermeability, promoting the development and progression of various disease processes. Notably, the lungs are a highly vulnerable organ wherein pulmonary inflammation and infection result in vascular leakage. Herein, we showed that Rap1, a small GTPase, plays an essential role for maintaining pulmonary endothelial barrier function in mice. Endothelial cell-specific Rap1a/Rap1b double knockout mice exhibited severe pulmonary edema. They also showed vascular leakage in the hearts, but not in the brains. En face analyses of the pulmonary arteries and 3D-immunofluorescence analyses of the lungs revealed that Rap1 potentiates VE-cadherin-mediated endothelial cell-cell junctions through dynamic actin cytoskeleton reorganization. Rap1 inhibits formation of cytoplasmic actin bundles perpendicularly binding VE-cadherin adhesions through inhibition of a Rho-ROCK pathway-induced activation of cytoplasmic nonmuscle myosin II (NM-II). Simultaneously, Rap1 induces junctional NM-II activation to create circumferential actin bundles, which anchor and stabilize VE-cadherin at cell-cell junctions. We also showed that the mice carrying only one allele of either Rap1a or Rap1b out of the two Rap1 genes are more vulnerable to lipopolysaccharide (LPS)-induced pulmonary vascular leakage than wild-type mice, while activation of Rap1 by administration of 007, an activator for Epac, attenuates LPS-induced increase in pulmonary endothelial permeability in wild-type mice. Thus, we demonstrate that Rap1 plays an essential role for maintaining pulmonary endothelial barrier functions under physiological conditions and provides protection against inflammation-induced pulmonary vascular leakage.

    DOI： 10.1096/fj.202300830RR

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  • Novel regulatory mechanisms underlying angiogenesis during wound healing revealed by fluorescence-based live-imaging in zebrafish. 国際誌

    Shinya Yuge, Tomohiro Ishii, Chikage Noishiki, Shigetomo Fukuhara

    Journal of biochemistry   2023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）  

    Angiogenesis is a dynamic morphogenetic process that refers to the growth of new blood vessels from the pre-existing vessels and is critical for tissue repair during wound healing. In adult normal tissues, quiescent endothelial cells and pericytes maintain vascular integrity, whereas angiogenesis is immediately induced upon tissue injury, thereby forming neovascular networks to maintain homeostasis. However, impaired angiogenesis results in development of chronic and non-healing wounds in various diseases such as diabetes and peripheral artery diseases. Zebrafish are a vertebrate model organism widely used for studying many medical and life science fields. Indeed, the molecular and cellular mechanisms underlying regulation of wound angiogenesis have recently been studied by performing fluorescence-based live-imaging of adult zebrafish. In this review, we describe how endothelial cells and pericytes establish neovascular networks during wound angiogenesis and also introduce a novel role of blood flow-driven intraluminal pressure in regulating angiogenesis during wound healing.

    DOI： 10.1093/jb/mvad024

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  • Mechanical loading of intraluminal pressure mediates wound angiogenesis by regulating the TOCA family of F-BAR proteins 査読 国際誌

    Shinya Yuge, Koichi Nishiyama, Yuichiro Arima, Yasuyuki Hanada, Eri Oguri-Nakamura, Sanshiro Hanada, Tomohiro Ishii, Yuki Wakayama, Urara Hasegawa, Kazuya Tsujita, Ryuji Yokokawa, Takashi Miura, Toshiki Itoh, Kenichi Tsujita, Naoki Mochizuki, Shigetomo Fukuhara

    Nature Communications   13 ( 1 )   2594 - 2594   2022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）   出版者・発行元：Springer Science and Business Media LLC  

    Abstract

    Angiogenesis is regulated in coordinated fashion by chemical and mechanical cues acting on endothelial cells (ECs). However, the mechanobiological mechanisms of angiogenesis remain unknown. Herein, we demonstrate a crucial role of blood flow-driven intraluminal pressure (IP) in regulating wound angiogenesis. During wound angiogenesis, blood flow-driven IP loading inhibits elongation of injured blood vessels located at sites upstream from blood flow, while downstream injured vessels actively elongate. In downstream injured vessels, F-BAR proteins, TOCA1 and CIP4, localize at leading edge of ECs to promote N-WASP-dependent Arp2/3 complex-mediated actin polymerization and front-rear polarization for vessel elongation. In contrast, IP loading expands upstream injured vessels and stretches ECs, preventing leading edge localization of TOCA1 and CIP4 to inhibit directed EC migration and vessel elongation. These data indicate that the TOCA family of F-BAR proteins are key actin regulatory proteins required for directed EC migration and sense mechanical cell stretching to regulate wound angiogenesis.

    DOI： 10.1038/s41467-022-30197-8

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    その他リンク： https://www.nature.com/articles/s41467-022-30197-8

  • Blood Flow Regulates Glomerular Capillary Formation in Zebrafish Pronephros 査読

    Yusuke Nishimura, Tomohiro Ishii, Koji Ando, Shinya Yuge, Hiroyuki Nakajima, Weibin Zhou, Naoki Mochizuki, Shigetomo Fukuhara

    Kidney360   3 ( 4 )   700 - 713   2022年4月

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    担当区分：筆頭著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：American Society of Nephrology (ASN)  

    Background

    <p>The renal glomerulus is a tuft of capillaries in Bowman’s capsule and functions as a blood-filtration unit in the kidney. The unique glomerular capillary tuft structure is relatively conserved through vertebrate species. However, the morphogenetic mechanism governing glomerular capillary tuft formation remains elusive.

    </p>Methods

    <p>To clarify how glomerular capillaries develop, we analyzed glomerular capillary formation in the zebrafish pronephros by exploiting fluorescence-based bio-imaging technology.

    </p>Results

    <p>During glomerular capillary formation in the zebrafish pronephros, endothelial cells initially sprouted from the dorsal aorta and formed the capillaries surrounding the bilateral glomerular primordia in response to podocyte progenitor-derived vascular endothelial growth factor-A. After formation, blood flow immediately occurred in the glomerular primordia-associated capillaries, while in the absence of blood flow, they were transformed into sheet-like structures enveloping the glomerular primordia. Subsequently, blood flow induced formation of Bowman’s space at the lateral sides of the bilateral glomerular primordia. Concomitantly, podocyte progenitors enveloped their surrounding capillaries while moving toward and coalescing at the midline. These capillaries then underwent extensive expansion and remodeling to establish a functional glomerular capillary tuft. However, stopping blood flow inhibited the remodeling of bilateral glomerular primordia, which therefore remained unvascularized but covered by the vascular sheets.

    </p>Conclusions

    <p>We delineated the morphogenetic processes governing glomerular capillary tuft formation in the zebrafish pronephros and demonstrated crucial roles of blood flow in its formation. Blood flow maintains tubular structures of the capillaries surrounding the glomerular primordia and promotes glomerular incorporation of these vessels by inducing the remodeling of glomerular primordia.

    </p>

    DOI： 10.34067/kid.0005962021

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  • ライブイメージングにより血管新生におけるペリサイトの真の機能を解明する

    石井 智裕, 弓削 進弥, 安藤 康史, 福原 茂朋

    日本医科大学医学会雑誌   18 ( 1 )   70 - 71   2022年2月

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  • Zebrafish Vascular Mural Cell Biology: Recent Advances, Development, and Functions. 査読 国際誌

    Koji Ando, Tomohiro Ishii, Shigetomo Fukuhara

    Life (Basel, Switzerland)   11 ( 10 )   2021年10月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Recruitment of mural cells to the vascular wall is essential for forming the vasculature as well as maintaining proper vascular functions. In recent years, zebrafish genetic tools for mural cell biology have improved substantially. Fluorescently labeled zebrafish mural cell reporter lines enable us to study, with higher spatiotemporal resolution than ever, the processes of mural cell development from their progenitors. Furthermore, recent phenotypic analysis of platelet-derived growth factor beta mutant zebrafish revealed well-conserved organotypic mural cell development and functions in vertebrates with the unique features of zebrafish. However, comprehensive reviews of zebrafish mural cells are lacking. Therefore, herein, we highlight recent advances in zebrafish mural cell tools. We also summarize the fundamental features of zebrafish mural cell development, especially at early stages, and functions.

    DOI： 10.3390/life11101041

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  • 脈管のメカノバイオロジー 創傷治癒過程の血管新生における内腔圧の新たな役割の解明

    福原 茂朋, 弓削 進弥, 有馬 勇一郎, 花田 保之, 花田 三四郎, 石井 智裕, 若山 勇紀, 横川 隆司, 三浦 岳, 望月 直樹, 西山 功一

    脈管学   60 ( Suppl. )   S113 - S114   2020年10月

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    記述言語：日本語   出版者・発行元：(一社)日本脈管学会  

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  • SIMPLE binds specifically to PI4P through SIMPLE-like domain and participates in protein trafficking in the trans-Golgi network and/or recycling endosomes. 査読 国際誌

    Moriwaki Y, Ohno Y, Ishii T, Takamura Y, Kita Y, Watabe K, Sango K, Tsuji S, Misawa H

    PLoS One   13 ( 6 )   e0199829   2018年6月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    DOI： 10.1371/journal.pone.0199829

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  • L-leucine and SPNS1 coordinately ameliorate dysfunction of autophagy in mouse and human Niemann-Pick type C disease 査読

    Hiroko Yanagisawa, Tomohiro Ishii, Kentaro Endo, Emiko Kawakami, Kazuaki Nagao, Toshiyuki Miyashita, Keiko Akiyama, Kazuhiko Watabe, Masaaki Komatsu, Daisuke Yamamoto, Yoshikatsu Eto

    SCIENTIFIC REPORTS   7 ( 1 )   15944   2017年11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：NATURE PUBLISHING GROUP  

    Lysosomal storage disorders are characterized by progressive accumulation of undigested macromolecules within the cell due to lysosomal dysfunction. 573C10 is a Schwann cell line derived from a mouse model of Niemann-Pick type C disease-1, NPC (-/-). Under serum-starved conditions, NPC (-/-) cells manifested impaired autophagy accompanied by an increase in the amount of p62 and lysosome enlargement. Addition of L-leucine to serum-starved NPC (-/-) cells ameliorated the enlargement of lysosomes and the p62 accumulation. Similar autophagy defects were observed in NPC (-/-) cells even without serum starvation upon the knockdown of Spinster-like 1 (SPNS1), a putative transporter protein thought to function in lysosomal recycling. Conversely, SPNS1 overexpression impeded the enlargement of lysosomes, p62 accumulation and mislocalization of the phosphorylated form of the mechanistic Target of rapamycin in NPC (-/-) cells. In addition, we found a reduction in endogenous SPNS1 expression in fibroblasts derived from NPC-1 patients compared with normal fibroblasts. We propose that SPNS1-dependent L-leucine export across the lysosomal membrane is a key step for triggering autophagy, and that this mechanism is impaired in NPC-1.

    DOI： 10.1038/s41598-017-15305-9

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  • Myelinating cocultures of rodent stem cell line-derived neurons and immortalized Schwann cells 査読

    Tomohiro Ishii, Emiko Kawakami, Kentaro Endo, Hidemi Misawa, Kazuhiko Watabe

    NEUROPATHOLOGY   37 ( 5 )   475 - 481   2017年10月

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    担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

    Myelination is one of the most remarkable biological events in the neuron-glia interactions for the development of the mammalian nervous system. To elucidate molecular mechanisms of cell-to-cell interactions in myelin synthesis in vitro, establishment of the myelinating system in cocultures of continuous neuronal and glial cell lines are desirable. In the present study, we performed co-culture experiments using rat neural stem cell-derived neurons or mouse embryonic stem (ES) cell-derived motoneurons with immortalized rat IFRS1 Schwann cells to establish myelinating cultures between these cell lines. Differentiated neurons derived from an adult rat neural stem cell line 1464R or motoneurons derived from a mouse ES cell line NCH4.3, were mixed with IFRS1 Schwann cells, plated, and maintained in serum-free F12 medium with B27 supplement, ascorbic acid, and glial cell line-derived neurotrophic factor. Myelin formation was demonstrated by electron microscopy at 4weeks in cocultures of 1464R-derived neurons or NCH4.3-derived motoneurons with IFRS1 Schwann cells. These in vitro coculture systems utilizing the rodent stable stem and Schwann cell lines can be useful in studies of peripheral nerve development and regeneration.

    DOI： 10.1111/neup.12397

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  • Formation and spreading of TDP-43 aggregates in cultured neuronal and glial cells demonstrated by time-lapse imaging 査読

    Tomohiro Ishii, Emiko Kawakami, Kentaro Endo, Hidemi Misawa, Kazuhiko Watabe

    PLOS ONE   12 ( 6 )   e0179375   2017年6月

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    担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

    TAR DNA-binding protein 43 (TDP-43) is a main constituent of cytoplasmic aggregates in neuronal and glial cells in cases of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. We have previously demonstrated that adenovirus-transduced artificial TDP-43 cytoplasmic aggregates formation is enhanced by proteasome inhibition in vitro and in vivo. However, the relationship between cytoplasmic aggregate formation and cell death remains unclear. In the present study, rat neural stem cell lines stably transfected with EGFP- or Sirius-expression vectors under the control of tubulin beta III, glial fibrillary acidic protein, or 2',3'-cyclic nucleotide 3'-phosphodiesterase promoter were differentiated into neurons, astrocytes, and oligodendrocytes, respectively, in the presence of retinoic acid. The differentiated cells were then transduced with adenoviruses expressing DsRed-tagged human wild type and C-terminal fragment TDP-43 under the condition of proteasome inhibition. Time-lapse imaging analyses revealed growing cytoplasmic aggregates in the transduced neuronal and glial cells, followed by collapse of the cell. The aggregates remained insoluble in culture media, consisted of sarkosyl-insoluble granular materials, and contained phosphorylated TDP-43. Moreover, the released aggregates were incorporated into neighboring neuronal cells, suggesting cell-to-cell spreading. The present study provides a novel tool for analyzing the detailed molecular mechanisms of TDP-43 proteinopathy in vitro.

    DOI： 10.1371/journal.pone.0179375

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  • IL-22/STAT3-Induced Increases in SLURP1 Expression within Psoriatic Lesions Exerts Antimicrobial Effects against Staphylococcus aureus 査読

    Yasuhiro Moriwaki, Kiyoko Takada, Toshinori Nagasaki, Natsuki Kubo, Tomohiro Ishii, Kazuaki Kose, Taihei Kageyama, Shoutaro Tsuji, Koichiro Kawashima, Hidemi Misawa

    PLOS ONE   10 ( 10 )   e0140750   2015年10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：PUBLIC LIBRARY SCIENCE  

    Background
    SLURP1 is the causal gene for Mal de Meleda (MDM), an autosomal recessive skin disorder characterized by diffuse palmoplantar keratoderma and transgressive keratosis. Moreover, although SLURP1 likely serves as an important proliferation/differentiation factor in keratinocytes, the possible relation between SLURP1 and other skin diseases, such as psoriasis and atopic dermatitis, has not been studied, and the pathophysiological control of SLURP1 expression in keratinocytes is largely unknown.
    Objectives
    Our aim was to examine the involvement of SLURP1 in the pathophysiology of psoriasis using an imiquimod (IMQ)-induced psoriasis model mice and normal human epidermal keratinocytes (NHEKs).
    Results
    SLURP1 expression was up-regulated in the skin of IMQ-induced psoriasis model mice. In NHEKs stimulated with the inflammatory cytokines IL-17, IL-22 and TNF-alpha, which are reportedly expressed in psoriatic lesions, SLURP1 mRNA expression was significantly up-regulated by IL-22 but not the other two cytokines. The stimulatory effect of IL-22 was completely suppressed in NHEKs treated with a STAT3 inhibitor or transfected with siRNA targeting STAT3. Because IL-22 induces production of antimicrobial proteins in epithelial cells, the antibacterial activity of SLURP1 was assessed against Staphylococcus aureus (S. aureus), which is known to be associated with disease severity in psoriasis. SLURP1 significantly suppressed the growth of S. aureus.
    Conclusions
    These results indicate SLURP1 participates in pathophysiology of psoriasis by regulating keratinocyte proliferation and differentiation, and by suppressing the growth of S. aureus.

    DOI： 10.1371/journal.pone.0140750

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  • Adenoviral expression of TDP-43 and FUS genes and shRNAs for protein degradation pathways in rodent motoneurons in vitro and in vivo 査読

    Kazuhiko Watabe, Keiko Akiyama, Emiko Kawakami, Tomohiro Ishii, Kentaro Endo, Hiroko Yanagisawa, Kazunori Sango, Masami Tsukamoto

    NEUROPATHOLOGY   34 ( 1 )   83 - 98   2014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）   出版者・発行元：WILEY-BLACKWELL  

    Formation of cytoplasmic aggregates in neuronal and glial cells is one of the pathological hallmarks of amyotrophic lateral sclerosis (ALS). Mutations in two genes encoding transactivation response (TAR) DNA-binding protein 43 (TDP-43) and fused in sarcoma (FUS), both of which are main constituents of cytoplasmic aggregates, have been identified in patients with familial and sporadic ALS. Impairment of protein degradation machineries has also been recognized to participate in motoneuron degeneration in ALS. In the present study, we produced recombinant adenovirus vectors encoding wild type and mutant TDP-43 and FUS, and those encoding short hairpin RNAs (shRNAs) for proteasome (PSMC1), autophagy (ATG5), and endosome (VPS24) systems to investigate whether the coupled gene transductions in motoneurons by these adenoviruses elicit ALS pathology. Cultured neurons, astrocytes and oligodendrocytes differentiated from adult rat neural stem cells and motoneurons derived from mouse embryonic stem cells were successfully infected with these adenoviruses showing cytoplasmic aggregate formation. When these adenoviruses were injected into the facial nerves of adult rats, exogenous TDP-43 and FUS proteins were strongly expressed in facial motoneurons by a retrograde axonal transport of the adenoviruses. Co-infections of adenovirus encoding shRNA for PSMC1, ATG5 or VPS24 with TDP-43 or FUS adenovirus enhanced cytoplasmic aggregate formation in facial motoneurons, suggesting that impairment of protein degradation pathways accelerates formation of TDP-43 and FUS-positive aggregates in ALS.

    DOI： 10.1111/neup.12058

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▼全件表示

MISC

  • 造血幹細胞がつくられる新たなしくみ

    福原 茂朋, 盧 承湜, 小栗 エリ, 山本 清威, 石井 智裕

    生体の科学   Vol.71 ( No.4 )   359 - 363   2020年8月

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    記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

    DOI： 10.11477/mf.2425201190

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  • 血流に起因する内腔圧による創傷治癒過程の血管新生の新たな制御機構

    福原茂朋, 弓削進弥, 西山功一, 有馬勇一郎, 花田保之, 花田三四郎, 石井智裕, 若山勇紀, 辻田和也, 横川隆司, 三浦岳, 望月直樹

    日本生化学会大会(Web)   93rd   [3S06m - 01]   2020年

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    記述言語：日本語   出版者・発行元：(公社)日本生化学会  

    J-GLOBAL

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  • 内腔圧の機械的刺激により制御される創傷治癒での血管新生

    弓削進弥, 西山功一, 有馬勇一郎, 花田保之, 花田三四郎, 石井智裕, 若山勇紀, 辻田和也, 横川隆司, 三浦岳, 望月直樹, 福原茂朋

    日本生化学会大会(Web)   93rd   [3S06a - 03]   2020年

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    記述言語：日本語   出版者・発行元：(公社)日本生化学会  

    J-GLOBAL

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  • SPNS1は、ニーマンピック病C型のオートファジー不全と関連している

    柳澤 比呂子, 秋山 けい子, 石井 智裕, 渡部 和彦, 遠藤 堅太郎, 河上 江美子, 小松 雅明, 山元 大輔, 衞藤 義勝

    生命科学系学会合同年次大会   2017年度   [2P - 0305]   2017年12月

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    記述言語：日本語   出版者・発行元：生命科学系学会合同年次大会運営事務局  

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  • ロイシン添加によるオートファジー不全を改善するメカニズムとSpin1との関連

    柳澤 比呂子, 石井 智裕, 河上 江美子, 遠藤 堅太郎, 平岡 由佳, 上野 隆, 山元 大輔, 小松 雅明, 渡部 和彦

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集   88回・38回   [2P0064] - [2P0064]   2015年12月

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    記述言語：日本語   出版者・発行元：(公社)日本生化学会  

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  • Studies on pathomechanisms of demyalination caused by the mutation of SIMPLE, the causative gene for CMT1C

    Tomohiro Ishii, Yasuhiro Moriwaki, Kazuhiko Watabe, Hidemi Misawa

    JOURNAL OF PHARMACOLOGICAL SCIENCES   121   233P - 233P   2013年

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    記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：JAPANESE PHARMACOLOGICAL SOC  

    Web of Science

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  • 組換えウイルスによる成体ラット・マウス運動ニューロンへのALS関連遺伝子導入

    渡部和彦, 秋山けい子, 河上江美子, 石井智裕, 柳澤比呂子, 三五一憲, 塚本雅美, 岡戸晴生, 三輪昭子, 三宅弘一

    日本神経学会学術大会プログラム・抄録集   54th   2013年

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▼全件表示

受賞

  • 優秀賞

    2020年11月   血管生物医学会若手研究会   ペリサイトによる血管新生制御機構の解明

    石井智裕, 弓削進弥, 安藤康史, 福原茂朋

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  • Best Poster Award

    2014年9月   国際神経病理学会   Retrograde axonal delivery of TDP-43 and FUS genes using AAV9 and lentivirus vectors to adult mouse motoneurons.

    Ishii T, Akiyama K, Kawakami E, Yanagisawa H, Sango K, Okado H, Miwa A, Miyake K, Kato S, Kobayashi K, Misawa H, Watabe K

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    受賞区分：国際学会・会議・シンポジウム等の賞  受賞国：ブラジル連邦共和国

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共同研究・競争的資金等の研究課題

  • 生理的および病的な血管新生におけるペリサイトの機能とその制御機構の解明

    研究課題/領域番号：21K15346  2021年4月 - 2024年3月

    日本学術振興会  科学研究費助成事業  若手研究

    石井 智裕

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    配分額：4680000円 （ 直接経費：3600000円 、 間接経費：1080000円 ）

    ペリサイトは内皮細胞を被覆することで安定な血管構造を維持している．組織が創傷などを受けると，血管新生が誘導され，新たな血管網が形成され組織の修復，恒常性維持に寄与する．一方，がんなど病態時では，過剰な血管新生が生じ，逆に病態を悪化させることが知られているが，この病的血管ではペリサイトのない血管ができることが特徴であり，ペリサイトによる血管の被覆が正常な血管新生に重要であることが示唆されるが，血管新生を制御する機能はいまだ明らかとなっていない．本研究では，申請者の所属する研究室で開発した成体ゼブラフィッシュの蛍光ライブイメージング技術を駆使することで，生体内の血管新生を生きたまま観察し，ペリサイトによる血管新生の制御機構を明らかとすることで血管新生が生体にとって相反する効果を発揮するメカニズムの解明を目指す．
    １年目では，生理的条件における血管新生過程のペリサイトの役割を明らかとするために，まず血管内皮細胞とペリサイトを可視化し，かつペリサイトをコンディショナルに除去できる魚の樹立した．次に，この魚が成体となってから任意のタイミングでペリサイトを除去する条件検討を行った．ペリサイトを除去できる条件が確立したため，通常およびペリサイトを除去した成魚の皮膚へ創傷を与え，創傷治癒時の血管新生を誘導し，ライブイメージングにより，血管新生過程を経時的に観察した．現在，イメージングによる解析から，ペリサイトが血管新生のどのプロセスを制御するかについて詳細な解析を行っている．

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