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YOSHIKAWA YokoGraduate School of Science, Technology and Innovation / Department of Science, Technology and InnovationAssociate Professor
Research activity information
■ Award- Jul. 2019 Asia Pacific Society for Biology and Medical Sciences, Outstanding research achivement and contribution to APSBMS, Ras inhibitors: Potential agents having both anti-proliferative and anti-metastatic properties
- Oct. 2013 神戸大学 新緑会, 第1回新緑会ヤングインベスティゲーターアワード優秀賞, 新規Ras機能阻害剤Kobe0065ファミリー化合物のがん転移抑制メカニズムの解析Others
- Feb. 2008 神戸大学大学院医学系研究科, 神戸大学大学院医学系研究科 優秀賞, 低分子量GTP結合蛋白質Rasを標的とした新規抗癌剤の探索
- Dec. 2006 Kobe University 21th Century COE Program International Symposium, The Best Presentation Award, RA-GEF-2 mediates a crosstalk between small GTPases M-Ras and Rap1 to control integrin-dependent cell adhesion in lymphocytes
- Background: We have shown that phospholipase Cε (PLCε), an effector of Ras and Rap1 small GTPases, plays pivotal roles in inflammation and inflammation-associated carcinogenesis by augmenting proinflammatory cytokine production from epithelial cells of various organs. The purpose of this study is to analyze its role in neutrophilic alveolar inflammation accompanying acute lungBioMed Central, Jan. 2019, Respiratory Research, 20(9) (9), 1 - 12, English, International magazine[Refereed]Scientific journal
- Sep. 2018, Biochemistry, 57(36) (36), 5350 - 5358, EnglishMolecular Basis for Allosteric Inhibition of GTP-Bound H-Ras Protein by a Small-Molecule Compound Carrying a Naphthalene Ring.[Refereed]Scientific journal
- Metastasis stands as the major obstacle for the survival from cancers. Nonetheless most existing anti-cancer drugs inhibit only cell proliferation, and discovery of agents having both anti-proliferative and anti-metastatic properties would be more beneficial. We previously reported the discovery of small-molecule Ras inhibitors, represented by Kobe0065, that displayed anti-proliferative activity on xenografts of human colorectal cancer (CRC) cell line SW480 carrying the K-ras(G12V) gene. Here we show that treatment of cancer cells carrying the activated ras genes with Kobe0065 or a siRNA targeting Ras downregulates the expression of lysyl oxidase (LOX), which has been implicated in metastasis. LOX expression is enhanced by co-expression of Ras(G12V) through activation of phosphatidylinositol 3-kinase (PI3K)/Akt and concomitant accumulation of hypoxia-inducible factor (HIF)-1 alpha. Furthermore, Kobe0065 effectively inhibits not only migration and invasion of cancer cells carrying the activated ras genes but also lung metastasis of human CRC cell line SW620 carrying the K-ras(G12V) gene. Collectively, these results indicate that Kobe0065 prevents metastasis through inhibition of the Ras-P13K-Akt-HIF-1 alpha-LOX signaling and suggest that Ras inhibitors in general might exhibit both anti-proliferative and anti-metastatic properties toward cancer cells carrying the activated ras genes. (C) 2017 Elsevier B.V. All rights reserved.ELSEVIER IRELAND LTD, Dec. 2017, CANCER LETTERS, 410, 82 - 91, English[Refereed]Scientific journal
- Rapgef2 and Rapgef6 define a subfamily of guanine nucleotide exchange factors for Rapl, characterized by possession of the Ras/Rap-associating domains and implicated in the etiology of schizophrenia. We previously found that dorsal telencephalon-specific Rapgef2 conditional knockout mice exhibits severe defects in formation of apical surface adherence junctions (AJs) and localization of radial glial cells (RGCs). In this study, we analyze the underlying molecular mechanism by using primary cultures of RGCs established from the developing cerebral cortex. The results show that Rapgef2-deficient RGCs exhibit a decreased ability of neurosphere formation, morphological changes represented by regression of radial glial (RG) fibers and reduced expression of AJ-constituent proteins such as N-cadherin, zonula occludens1, E-cadherin and beta-catenin. Moreover, siRNA-mediated knockdown of Rapgef2 or RaplA inhibits the AJ protein expression and RG fiber formation while overexpression of Rapgef2, Rapgef6, Rap1A(GI2v) or Rap1B(G12v) in Rapgef2-deficient RGCs restores them. Furthermore, Rapgef2-deficient RGCs exhibit a reduction in phosphorylation of extracellular signal-regulated kinase (ERK) leading to downregulation of the expression of c-jun, which is implicated in the AJ protein expression. These results indicate a crucial role of the Rapgef2-Rap1A-ERK-c-jun pathway in regulation of the AJ formation in RGCs. (C) 2017 Elsevier Inc. All rights reserved.ACADEMIC PRESS INC ELSEVIER SCIENCE, Nov. 2017, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 493(1) (1), 139 - 145, English[Refereed]Scientific journal
- Ras undergoes post-translational modifications including farnesylation, proteolysis, and carboxymethylation at the C terminus, which are necessary for membrane recruitment and effector recognition. Full activation of c-Raf-1 requires cooperative interaction of the farnesylated C terminus and the activator region of Ras with its cysteine-rich domain (CRD). However, the molecular basis for this interaction remains unclear because of difficulties in preparing modified Ras in amounts sufficient for structural studies. Here, we use Sortase A-catalyzed protein ligation to prepare modified Ras in sufficient amounts for NMR and X-ray crystallographic analyses. The results show that the farnesylated C terminus establishes an intramolecular interaction with the catalytic domain and brings the farnesyl moiety to the proximity of the activator region, which may be responsible for their cooperative recognition of c-Raf-1-CRD.WILEY, Aug. 2017, FEBS LETTERS, 591(16) (16), 2470 - 2481, English[Refereed]Scientific journal
- In human genetic studies of schizophrenia, we uncovered copy-number variants in RAPGEF6 and RAPGEF2 genes. To discern the effects of RAPGEF6 deletion in humans, we investigated the behavior and neural functions of a mouse lacking Rapgef6. Rapgef6 deletion resulted in impaired amygdala function measured as reduced fear conditioning and anxiolysis. Hippocampal-dependent spatial memory and prefrontal cortex-dependent working memory tasks were intact. Neural activation measured by cFOS phosphorylation demonstrated a reduction in hippocampal and amygdala activation after fear conditioning, while neural morphology assessment uncovered reduced spine density and primary dendrite number in pyramidal neurons of the CA3 hippocampal region of knockout mice. Electrophysiological analysis showed enhanced long-term potentiation at cortico-amygdala synapses. Rapgef6 deletion mice were most impaired in hippocampal and amygdalar function, brain regions implicated in schizophrenia pathophysiology. The results provide a deeper understanding of the role of the amygdala in schizophrenia and suggest that RAPGEF6 may be a novel therapeutic target in schizophrenia.NATURE PUBLISHING GROUP, Jun. 2015, TRANSLATIONAL PSYCHIATRY, 5(6) (6), English[Refereed]Scientific journal
- Mutational activation of the Ras oncogene products (H-Ras, K-Ras, and N-Ras) is frequently observed in human cancers, making them promising anticancer drug targets. Nonetheless, no effective strategy has been available for the development of Ras inhibitors, partly owing to the absence of well-defined surface pockets suitable for drug binding. Only recently, such pockets have been found in the crystal structures of a unique conformation of Ras center dot GTP. Here we report the successful development of small-molecule Ras inhibitors by an in silico screen targeting a pocket found in the crystal structure of M-Ras center dot GTP carrying an H-Ras-type substitution P40D. The selected compound Kobe0065 and its analog Kobe2602 exhibit inhibitory activity toward H-Ras center dot GTP-c-Raf-1 binding both in vivo and in vitro. They effectively inhibit both anchorage-dependent and -independent growth and induce apoptosis of H-ras(G12V)-transformed NIH 3T3 cells, which is accompanied by down-regulation of downstream molecules such as MEK/ERK, Akt, and RalA as well as an upstream molecule, Son of sevenless. Moreover, they exhibit antitumor activity on a xenograft of human colon carcinoma SW480 cells carrying the K-ras(G12V) gene by oral administration. The NMR structure of a complex of the compound with H-Ras center dot GTP(T35S), exclusively adopting the unique conformation, confirms its insertion into one of the surface pockets and provides a molecular basis for binding inhibition toward multiple Ras center dot GTP-interacting molecules. This study proves the effectiveness of our strategy for structure-based drug design to target Ras center dot GTP, and the resulting Kobe0065-family compounds may serve as a scaffold for the development of Ras inhibitors with higher potency and specificity.NATL ACAD SCIENCES, May 2013, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 110(20) (20), 8182 - 8187, English[Refereed]Scientific journal
- Ras proteins, particularly their active GTP-bound forms (Ras·GTP), were thought "undruggable" owing to the absence of apparent drug-accepting pockets in their crystal structures. Only recently, such pockets have been found in the crystal structures representing a novel Ras·GTP conformation. We have conducted an in silico docking screen targeting a pocket in the crystal structure of M-RasP40D·GTP and obtained Kobe0065, which, along with its analogue Kobe2602, inhibits binding of H-Ras·GTP to c-Raf-1. They inhibit the growth of H-rasG12V-transformed NIH3T3 cells, which are accompanied by downregulation of not only MEK/ERK but also Akt, RalA, and Sos, indicating the blockade of interaction with multiple effectors. Moreover, they exhibit antitumor activity on a xenograft of human colon carcinoma carrying K-rasG12V. The nuclear magnetic resonance structure of a complex of the compound with H-RasT35S·GTP confirms its insertion into the surface pocket. Thus, these compounds may serve as a novel scaffold for the development of Ras inhibitors with higher potency and specificity. © 2013 Elsevier Inc.2013, Enzymes, 34, 1 - 23, English[Refereed]Scientific journal
- Ras small GTPases undergo dynamic equilibrium of two interconverting conformations, state 1 and state 2, in the GTP-bound forms, where state 2 is recognized by effectors, whereas physiological functions of state 1 have been unknown. Limited information, such as static crystal structures and (31)P NMR spectra, was available for the study of the conformational dynamics. Here we determine the solution structure and dynamics of state 1 by multidimensional heteronuclear NMR analysis of an H-RasT35S mutant in complex with guanosine 5'-(beta, gamma-imido)triphosphate (GppNHp). The state 1 structure shows that the switch I loop fluctuates extensively compared with that in state 2 or H-Ras-GDP. Also, backbone (1)H, (15)N signals for state 2 are identified, and their dynamics are studied by utilizing a complex with c-Raf-1. Furthermore, the signals for almost all the residues of H-Ras.GppNHp are identified by measurement at low temperature, and the signals for multiple residues are found split into two peaks corresponding to the signals for state 1 and state 2. Intriguingly, these residues are located not only in the switch regions and their neighbors but also in the rigidly structured regions, suggesting that global structural rearrangements occur during the state interconversion. The backbone dynamics of each state show that the switch loops in state 1 are dynamically mobile on the picosecond to nanosecond time scale, and these mobilities are significantly reduced in state 2. These results suggest that multiconformations existing in state 1 are mostly deselected upon the transition toward state 2 induced by the effector binding.AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, Nov. 2011, JOURNAL OF BIOLOGICAL CHEMISTRY, 286(45) (45), 39644 - 39653, English[Refereed]Scientific journal
- Ras family small GTPases assume two interconverting conformations, "inactive" state 1 and "active" state 2, in their GTP-bound forms. Here, to clarify the mechanism of state transition, we have carried out x-ray crystal structure analyses of a series of mutant H-Ras and M-Ras in complex with guanosine 5'-(beta,gamma-imido) triphosphate (GppNHp), representing various intermediate states of the transition. Crystallization of H-RasT35S-GppNHp enables us to solve the first complete tertiary structure of H-Ras state 1 possessing two surface pockets unseen in the state 2 or H-Ras-GDP structure. Moreover, determination of the two distinct crystal structures of H-RasT35S-GppNHp, showing prominent polysterism in the switch I and switch II regions, reveals a pivotal role of the guanine nucleotide-mediated interaction between the two switch regions and its rearrangement by a nucleotide positional change in the state 2 to state 1 transition. Furthermore, the (31)P NMR spectra and crystal structures of the GppNHp-bound forms of M-Ras mutants, carrying various H-Ras-type amino acid substitutions, also reveal the existence of a surface pocket in state 1 and support a similar mechanism based on the nucleotide-mediated interaction and its rearrangement in the state 1 to state 2 transition. Intriguingly, the conformational changes accompanying the state transition mimic those that occurred upon GDP/GTP exchange, indicating a common mechanistic basis inherent in the high flexibility of the switch regions. Collectively, these results clarify the structural features distinguishing the two states and provide new insights into the molecular basis for the state transition of Ras protein.AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, Jul. 2010, JOURNAL OF BIOLOGICAL CHEMISTRY, 285(29) (29), 22696 - 22705, English[Refereed]Scientific journal
- A multitude of guanine nucleotide exchange factors (GEFs) regulate Rap1 small GTPases, however, their individual functions remain obscure. Here, we investigate the in vivo function of the Rap1 GEF RA-GEF-1. The expression of RA-GEF-1 in wild-type mice starts at embryonic day (E) 8.5, and continues thereafter. RA-GEF-1(-/-) mice appear normal until E7.5, but become grossly abnormal and dead by E9.5. This mid-gestation death appears to be closely associated with severe defects in yolk sac blood vessel formation. RA-GEF-1(-/-) yolk sacs form apparently normal blood islands by E8.5, but the blood islands fail to coalesce into a primary vascular plexus, indicating that vasculogenesis is impaired. Furthermore, RA-GEF-1(-/-) embryos proper show severe defects in the formation of major blood vessels. These results suggest that deficient Rap1 signaling may lead to defective vascular morphogenesis in the yolk sac and embryos proper. (C) 2007 Elsevier Inc. All rights reserved.ACADEMIC PRESS INC ELSEVIER SCIENCE, Nov. 2007, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 363(1) (1), 106 - 112, English[Refereed]Scientific journal
- The Rap1 small GTPase has been implicated in regulation of integrin-mediated leukocyte adhesion downstream of various chemokines and cytokines in many aspects of inflammatory and immune responses. However, the mechanism for Rap1 regulation in the adhesion signaling remains unclear. RA-GEF-2 is a member of the multiple-member family of guanine nucleotide exchange factors (GEFs) for Rap1 and characterized by the possession of a Ras/Rap1-associating domain, interacting with M-Ras-GTP as an effector, in addition to the GEF catalytic domain. Here, we show that RA-GEF-2 is specifically responsible for the activation of Rap1 that mediates tumor necrosis factor-alpha (TNF-alpha)-triggered integrin activation. In BAF3 hematopoietic cells, activated M-Ras potently induced lymphocyte function-associated antigen I (LFA-1)-mediated cell aggregation. This activation was totally abrogated by knockdown of RA-GEF-2 or Rap1. TNF-a treatment activated LFA-1 in a manner dependent on M-Ras, RA-GEF-2, and Rap1 and induced activation of M-Ras and Rap1 in the plasma membrane, which was accompanied by recruitment of RA-GEF-2. Finally, we demonstrated that M-Ras and RA-GEF-2 were indeed involved in TNF-alpha-stimulated and Rapi-mediated LFA-1 activation in splenocytes by using mice deficient in RA-GEF-2. These findings proved a crucial role of the cross-talk between two Ras-family GTPases M-Ras and Rap1, mediated by RA-GEF-2, in adhesion signaling.AMER SOC CELL BIOLOGY, Aug. 2007, MOLECULAR BIOLOGY OF THE CELL, 18(8) (8), 2949 - 2959, English[Refereed]Scientific journal
- Glyoxysomal malate dehydrogenase in pumpkin: Cloning of a cDNA and functional analysis of its presequenceGlyoxysomal malate dehydrogenase (gMDH) is an enzyme of the glyoxylate cycle that participates in degradation of storage oil, We have cloned a cDNA for gMDH from etiolated pumpkin cotyledons that encodes a polypeptide consisting of 356 amino acid residues, The nucleotide and N-terminal amino acid sequences revealed that gMDH is synthesized as a precursor with an N-terminal extrapeptide, The N-terminal presequence of 36 amino acid residues contains two regions homologous to those of other microbody proteins, which are also synthesized as large precursors, To investigate the functions of the N-terminal presequence of gMDH, we generated transgenic Arabidopsis that expressed a chimeric protein consisting of beta-glucuronidase and the N-terminal region of gMDH. Immunological and immunocytochemical studies revealed that the chimeric protein was imported into microbodies such as glyoxysomes and leaf peroxisomes and was then subsequently processed, Site-directed mutagenesis studies showed that the conserved amino acids in the N-terminal presequence, Arg-10 and His-17, function as recognition sites for the targeting to plant microbodies, and Cys-36 in the presequence is responsible for its processing. These results correspond to those from the analyses of glyoxysomal citrate synthase (gCS), which was also synthesized as a large precursor, suggesting that common mechanisms that can recognize the targeting or the processing of gMDH and gCS function in higher plant cells.JAPANESE SOC PLANT PHYSIOLOGISTS, Feb. 1998, PLANT AND CELL PHYSIOLOGY, 39(2) (2), 186 - 195, English[Refereed]Scientific journal
- A cDNA clone encoding the glyoxysomal malate synthase (EC 4.1.3.2) was identified by immunoscreening of a cDNA expression library constructed from poly(A)-rich RNA of etiolated pumpkin cotyledons. Determination of the DNA sequence of the 1979-nucleotide cDNA revealed a 1698-nucleotide open reading frame that encodes a polypeptide of 64632 Da. The identification of the cDNA for malate synthase was confirmed by matching three sequences obtained by peptide-sequence analyses of fragments generated by acid treatment of the purified enzyme. Northern blot analysis revealed that the probe hybridized to a single 2.3-kb species of mRNA species from etiolated pumpkin cotyledons which was not present in green pumpkin cotyledons. In a comparison of deduced amino acid sequences, pumpkin malate synthase was found to exhibit 83% and 48% similarity to the malate synthases from rape and Escherichia coli, respectively. Based on the amino acid sequence similarity and the hydropathy profiles of these malate synthases, the signal for targeting the enzyme to microbodies is discussed.SPRINGER VERLAG, Apr. 1991, EUROPEAN JOURNAL OF BIOCHEMISTRY, 197(2) (2), 331 - 336, English[Refereed]Scientific journal
- Despite the importance of ras as driver genes in many cancers, clinically effective anti-cancer drugs targeting their products, Ras, have been unavailable so far, which was in part ascribable to the apparently 'undruggable' nature of their tertiary structures. Nonetheless, recent studies in academia and industry have identified novel surface pockets accepting small-molecule ligands in both their active GTP-bound and inactive GDP-bound forms (Ras center dot GTP and Ras center dot GDP, respectively), which has led to a surge of investigations into the discovery of Ras-specific inhibitors particularly by utilizing their structural information for structure-based drug design (SBDD). We have been developing Ras inhibitors by SBDD targeting a novel conformation of Ras center dot GTP called state 1, possessing 'druggable' surface pockets, which emerges from the conformational dynamics. In this article, we will survey Ras functions from the structural biological point of view and summarize the current status of the development of Ras inhibitors including our own.OXFORD UNIV PRESS, Aug. 2015, JOURNAL OF BIOCHEMISTRY, 158(2) (2), 91 - 99, English[Refereed]Book review
- 日本放射光学会, 2014, 日本放射光学会誌 放射光, 27(1) (1), 3 - 9, Japaneserasがん遺伝子産物の新規立体構造情報を利用した分子標的がん治療薬の開発[Refereed]Introduction scientific journal
- Joint work, がん分子標的治療, 2015, Japaneseras がん遺伝子産物 Ras を分子標的としたがん治療薬開発の現状General book
- Others, Elsevier Inc., Dec. 2013, EnglishThe Enzymes, Vol. 34, Inhibitors of the Ras superfamily G-proteins, Part B / Discovery of Small-Molecule Ras Inhibitors that Display Antitumor Activity by Interfering with Ras・GTP?Effector InteractionScholarly book
- 第46回日本分子生物学会年会, Dec. 2023, JapaneseGTP加水分解酵素GAPによるRASのState認識機構Poster presentation
- 第96回日本生化学大会, Oct. 2023, Japanese光反応性GTPを用いたRASの不活性化機構の解明Oral presentation
- 第82回日本癌学会学術総会, Sep. 2023, EnglishDiscovery of RAS/RAF-binding inhibitors that allosterically disrupt RAF conformation and exert efficacy against RAS-driven cancersOral presentation
- 第95回日本生化学大会, Nov. 2022, Japanese低分子量Gタンパク質H-Rasのフリーズトラップ結晶構造解析によるGTPase活性分子メカニズムの追跡Poster presentation
- 第95回日本生化学大会, Nov. 2022, JapaneseSACLA/Spring-8/NMRを駆使した低分子量G蛋白質Rasの不活性化機構におけるアロステリック構造変化の解明Poster presentation
- The 42nd Annual Meeting of the Molecular Biology Society of Japan, Dec. 2019, EnglishRole of Ras in triple-negative breast cancerPoster presentation
- APMBMS 2019 Annual Meeting, Jul. 2019, English, International conferenceRas inhibitors : Potential agents having both anti-proliferative and anti-metastatic properties[Invited]Invited oral presentation
- 2018 Keystone Symposia Conference, Feb. 2018, English, Keystone Symposia on Molecular and Cellular Biology, Taos, USA, International conferenceDevelopment of Anti-Cancer and Anti-Inflammatory Drugs Targeting Phospholipase Cε(ポスター発表)Poster presentation
- 2018 Keystone Symposia Conference, Feb. 2018, English, Keystone Symposia on Molecular and Cellular Biology, Taos, USA, International conferenceDevelopment of Anti-Cancer and Anti-Inflammatory Drugs Targeting Phospholipase CεOral presentation
- 2017年度生命科学系学会合同年次大会(第40回日本分子生物学会年会 第90回日本生化学会大会), Dec. 2017, Japanese, 日本分子生物学会日本生化学会, 神戸, Domestic conferenceStructural basis for the intramolecular interaction to assemble the c-Raf-1 recognition site in posttranslationally modified H-Ras•GTPPoster presentation
- 2017年度生命科学系学会合同年次大会(第40回日本分子生物学会年会 第90回日本生化学会大会), Dec. 2017, Japanese, 日本分子生物学会日本生化学会, 神戸, Domestic conferenceAnti-Cancer and anti-inflammatory effect of specific inhibitors for Phospholipase Ce (PLCe)Poster presentation
- 2017年度生命科学系学会合同年次大会(第40回日本分子生物学会年会 第90回日本生化学会大会), Dec. 2017, Japanese, 日本分子生物学会日本生化学会, 神戸, Domestic conferenceNovel effect of Ras inhibitor and its application to cancer therapyPoster presentation
- 第76回 日本癌学会学術総会, Sep. 2017, Japanese, 日本癌学会, 横浜, International conferenceRas inhibitors display anti-metastatic effect toward ras-transformed cancer cells via downregulation of lysyl oxidaseOral presentation
- 75th Annual Meeting of Japanese Society of Radiology (JRC 2017), Apr. 2016, English, Japanese Society of Radiology, 横浜, Domestic conferenceDynamic CE-Perfusion MRI: Influence of Contrast Media Volume for Perfusion and Functional Assessments as Compared with Dynamic CE-Perfusion ADCTOral presentation
- 第72回日本癌学会学術総会, Oct. 2013, English, 日本癌学会, 横浜, Domestic conferenceAnalysis of the mechanism underlying the anti-metastatic action of Ras inhibitors by using a lung metastatic model mousePoster presentation
- American Society of Clinical Oncology 49th ANNUAL MEETING, May 2013, English, American Society of Clinical Oncology, Chicago, America, International conferenceASPAC01:Randomized phase III trial of adjuvant chemotherapy with gemcitabine versus s-1 for patients with resected pancreatic cancer.Others
- 2013 Gastrointestinal Cancers Symposium, Jan. 2013, Japanese, ASC, San Francisco, USA, International conferenceRandomized phase lll trial of adjuvant chemotherapy with gemcitabine versus S-1 for patients with resected pancreatic cancer (JASPAC-01 study).Oral presentation
- 第11回International Congress of the Asian Confederation for Physical Therapy, Oct. 2010, Japanese, International Congress of the Asian Confederation for Physical Therapy, Bali, International conferenceEvaluation of the combined use of ultrasound irradiation and wound dressing on pressure ulcersOral presentation
- 「G蛋白質シグナル」研究班会議, Sep. 2009, Japanese, 文部科学省特定領域研究, 千葉県・南房総市, Domestic conference低分子量GTP結合蛋白質Rasを標的とした新規抗癌剤の探索と展開Public symposium
- Kobe University Global COE Program International Symposium on Integrative Membrane Biology, Dec. 2008, English, グローバルCOE, 神戸, Domestic conferenceScreening for Ras specific inhibitors based on the conformational equilibrium of Ras in complex with GTPPoster presentation
- 特定研究領域「G蛋白質シグナル」研究班会議, Sep. 2008, Japanese, 特定研究領域「G蛋白質シグナル」, 新潟, Domestic conferenceGTP結合型H-Rasの高次構造多型性とエフェクターの新規認識機構Poster presentation
- 第3回グローバルCOE研究討論会 兼グローバルCOE第2回ワークショップ, Jul. 2008, Japanese, グローバルCOE, 淡路, Domestic conferenceNew strategy to develop Ras specific inhibitors based on conformational equilibrium of Ras oncoprotein.Poster presentation
- 第3回グローバルCOE研究討論会 兼グローバルCOE第2回ワークショップ, Jul. 2008, Japanese, グローバルCOE, 淡路, Domestic conferenceNew strategy to develop Ras specific inhibitorsPoster presentation
- 第3回グローバルCOE研究討論会 兼グローバルCOE第2回ワークショップ, Jul. 2008, Japanese, グローバルCOE, 淡路, Domestic conferenceFunctional analysis of Rap1 guanine nucleotide exchange factors RA-GEF-1 and RA-GEF-2Poster presentation
- BMB2007第30回日本分子生物学会年会、第80回日本生化学会大会合同大会, Dec. 2007, Japanese, 日本分子生物学会/日本生化学会, 横浜, Domestic conferenceConformational equilibrium of small GTPases and signal transductionPoster presentation
- Kobe University 21st Century COE Program International Symposium TOR-Signaling Mechanisms in the Cell Growth Regulation, Dec. 2006, English, 神戸大学21世紀COEプログラム「蛋白質のシグナル伝達機能」, 神戸, Domestic conferenceRA-GEF-2 mediates a crosstalk between small GTPases M-Ras and Rap1 to control integrin-dependent cell adhesion in lymphocytesOral presentation
- 日本分子生物学会2006フォーラム「分子生物学の未来」〜コンファレンス&サイエンティフィック・エキジビション〜, Dec. 2006, Japanese, 日本分子生物学会, 名古屋, Domestic conferenceRole of the Rap1 guanine nucleotide exchange factor RA-GEF-2 in M-Ras-mediated cell adhesionPoster presentation
- 第65回日本癌学会学術総会, Sep. 2006, Japanese, 日本癌学会, 横浜, Domestic conferenceRole of the guanine nucleotide exchange factor RA-GEF-2 in M-Ras-mediated cell adhesionPoster presentation
- 神戸大学21世紀COEプログラム「蛋白質のシグナル伝達機能」 平成18年度第1回研究発表会・若手ポスター発表会, Aug. 2006, Japanese, 神戸大学21世紀COEプログラム「蛋白質のシグナル伝達機能」, 神戸, Domestic conferenceRole of the Rap1 guanine nucleotide exchange factor RA-GEF-2 in M-Ras-mediated cell adhesionPoster presentation
■ Research Themes
- ひょうご科学技術協会, Apr. 2022 - Mar. 2025, Principal investigatorSACLAで挑む原子スケールでのがん化シグナル伝達機構の解明
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, Apr. 2022 - Mar. 2025薬剤耐性がんでの新規RAS/RAF結合阻害剤の薬効評価および作用機序の解明
- 学術研究助成基金助成金/基盤研究(C), Apr. 2018 - Mar. 2021, Principal investigatorCompetitive research funding
- 次世代がん医療創生研究事業(P-CREATE), Apr. 2016 - Mar. 2019, Coinvestigatorがん微小環境を制御するRas標的蛋白質PLCεの選択的阻害剤の開発