Research activity information

• 2007 財団法人阪大微生物病研究会優秀研究奨励賞


• 2007 日本薬学会近畿支部奨励賞


• 2006 日本生殖免疫学会学会賞

• Medullary cavity expansion is mediated by distinct cell populations during fetal bone development.

  Eriko Sumiya, Kohei Saeki, Kenta Nakano, Chie Kikutake, Noriko Kurisaki, Natsuko Nakaima, Mami Kurumata-Shigeto, Yumiko Kitada, Yuka Morioka, Yasuhiro Go, Mikita Suyama, Yuki Yoshimura, Motohito Goto, Mamoru Ito, Manabu Nakayama, Haruhiko Akiyama, Lucie Peduto, Tadashi Okamura, Yuki Matsushita, Shinichiro Sawa

  Bone marrow (BM) is the primary site of postnatal hematopoiesis, yet how it is established during embryogenesis remains poorly understood. BM formation is initiated by the invasion of vascular and mesenchymal cells into a preformed cartilage template, generating the primary ossification center (POC). Here, we identify CD55+CD90+ mesenchymal cells as early regulators of osteoclastogenesis within the POC. These cells share a matrix-degrading transcriptional program with FABP5+ septoclasts that localize to the chondro-osseous interface of developing bone. Fate-mapping analyses reveal that CD55+CD90+ cells transiently give rise to septoclasts during perinatal development, whereas osteoclast-supporting activity is subsequently assumed by LepR+ bone marrow stromal cells (BMSCs). During fracture repair, FABP5+ septoclasts and LepR+ BMSCs are redeployed within the callus, indicating reactivation of a developmental osteogenic program. Together, our findings uncover a conserved mechanism that links skeletal remodeling to the establishment of the BM microenvironment required for hematopoiesis.

  Apr. 2026, Nature communications, 17(1) (1), English, International magazine

  Scientific journal


• Correction: Expression of signal-transducing adaptor protein-1 attenuates experimental autoimmune hepatitis via down-regulating activation and homeostasis of invariant natural killer T cells.

  Jun-Ichi Kashiwakura, Kodai Saitoh, Takeru Ihara, Yuto Sasaki, Kota Kagohashi, Shiyo Enohara, Yuka Morioka, Hiroshi Watarai, Ryuta Muromoto, Yuichi Kitai, Kazuya Iwabuchi, Kenji Oritani, Tadashi Matsuda

  [This corrects the article DOI: 10.1371/journal.pone.0241440.].

  2021, PloS one, 16(4) (4), e0250536, English, International magazine


• Expression of signal-transducing adaptor protein-1 attenuates experimental autoimmune hepatitis via down-regulating activation and homeostasis of invariant natural killer T cells

  Jun-ichi Kashiwakura, Kodai Saitoh, Takeru Ihara, Yuto Sasaki, Kota Kagohashi, Shiyo Enohara, Yuka Morioka, Hiroshi Watarai, Ryuta Muromoto, Yuichi Kitai, Kazuya Iwabuchi, Kenji Oritani, Tadashi Matsuda

  Signal-transducing adaptor protein (STAP) family members function as adaptor molecules and are involved in several events during immune responses. Notably however, the biological functions of STAP-1 in other cells are not known. We aimed to investigate the functions of STAP-1 in invariant natural killer T (iNKT) cells and iNKT cell-dependent hepatitis. We employed concanavalin A (Con A)-induced hepatitis and α-galactosylceramide (α-GalCer)-induced hepatitis mouse models, both are models of iNKT cell-dependent autoimmune hepatitis, and STAP-1 overexpressing 2E10 cells to investigate the role of STAP-1 in iNKT cell activation in vivo an in vitro, respectively. After Con A- or α-GalCer-injection, hepatocyte necrotic areas and plasma alanine aminotransferase elevation were more severe in STAP-1 knockout (S1KO) mice and milder in lymphocyte-specific STAP-1 transgenic (S1Tg) mice, as compared to wild-type (WT) mice. Two events that may be related to Con A-induced and/or α-GalCer-induced hepatitis were influenced by STAP-1 manipulation. One is that iNKT cell populations in the livers and spleens were increased in S1KO mice and were decreased in S1Tg mice. The other is that Con A-induced interleukin-4 and interferon-γ production was attenuated by STAP-1 overexpression. These effects of STAP-1 were confirmed using 2E10 cells overexpressing STAP-1 that showed impairment of interleukin-4 and interferon-γ production as well as phosphorylation of Akt and mitogen-activated protein kinases in response to Con A stimulation. These results conclude that STAP-1 regulates iNKT cell maintenance/activation, and is involved in the pathogenesis of autoimmune hepatitis.

  Public Library of Science (PLoS), Nov. 2020, PLOS ONE, 15(11) (11), e0241440 - e0241440, English, International magazine

  Scientific journal


• Mutant p53-Expressing Cells Undergo Necroptosis via Cell Competition with the Neighboring Normal Epithelial Cells.

  Hirotaka Watanabe, Kojiro Ishibashi, Hiroki Mano, Sho Kitamoto, Nanami Sato, Kazuya Hoshiba, Mugihiko Kato, Fumihiko Matsuzawa, Yasuto Takeuchi, Takanobu Shirai, Susumu Ishikawa, Yuka Morioka, Toshiaki Imagawa, Kazuyasu Sakaguchi, Suguru Yonezawa, Shunsuke Kon, Yasuyuki Fujita

  p53 is a tumor suppressor protein, and its missense mutations are frequently found in human cancers. During the multi-step progression of cancer, p53 mutations generally accumulate at the mid or late stage, but not in the early stage, and the underlying mechanism is still unclear. In this study, using mammalian cell culture and mouse ex vivo systems, we demonstrate that when p53R273H- or p53R175H-expressing cells are surrounded by normal epithelial cells, mutant p53 cells undergo necroptosis and are basally extruded from the epithelial monolayer. When mutant p53 cells alone are present, cell death does not occur, indicating that necroptosis results from cell competition with the surrounding normal cells. Furthermore, when p53R273H mutation occurs within RasV12-transformed epithelia, cell death is strongly suppressed and most of the p53R273H-expressing cells remain intact. These results suggest that the order of oncogenic mutations in cancer development could be dictated by cell competition.

  Jun. 2018, Cell reports, 23(13) (13), 3721 - 3729, English, International magazine

  [Refereed]

  Scientific journal


• Nik-related kinase regulates trophoblast proliferation and placental development by modulating AKT phosphorylation

  Yuka Morioka, Jin-Min Nam, Takashi Ohashi

  Feb. 2017, PLOS ONE, 12(2) (2), e0171503, English

  [Refereed]

  Scientific journal


• Raftlin Controls Lipopolysaccharide-Induced TLR4 Internalization and TICAM-1 Signaling in a Cell Type-Specific Manner

  Megumi Tatematsu, Ryuji Yoshida, Yuka Morioka, Noriko Ishii, Kenji Funami, Ayako Watanabe, Kazuko Saeki, Tsukasa Seya, Misako Matsumoto

  May 2016, JOURNAL OF IMMUNOLOGY, 196(9) (9), 3865 - 3876, English

  [Refereed]

  Scientific journal


• DDX60 Is Involved in RIG-I-Dependent and Independent Antiviral Responses, and Its Function Is Attenuated by Virus-Induced EGFR Activation

  Hiroyuki Oshiumi, Moeko Miyashita, Masaaki Okamoto, Yuka Morioka, Masaru Okabe, Misako Matsumoto, Tsukasa Seya

  May 2015, CELL REPORTS, 11(8) (8), 1193 - 1207, English

  [Refereed]

  Scientific journal


• INAM Plays a Critical Role in IFN-gamma Production by NK Cells Interacting with Polyinosinic-Polycytidylic Acid-Stimulated Accessory Cells

  Jun Kasamatsu, Masahiro Azuma, Hiroyuki Oshiumi, Yuka Morioka, Masaru Okabe, Takashi Ebihara, Misako Matsumoto, Tsukasa Seya

  Nov. 2014, JOURNAL OF IMMUNOLOGY, 193(10) (10), 5199 - 5207, English

  [Refereed]

  Scientific journal


• Generation of Precise Point Mutation Mice by Footprintless Genome Modification

  Yuka Morioka, Yoshitaka Fujihara, Masaru Okabe

  Jan. 2014, GENESIS, 52(1) (1), 68 - 77, English

  [Refereed]

  Scientific journal


• Homologous Recombination in Rat Germline Stem Cells

  Mito Kanatsu-Shinohara, Megumi Kato-Itoh, Masahito Ikawa, Masanori Takehashi, Makoto Sanbo, Yuka Morioka, Takashi Tanaka, Hiroko Morimoto, Masumi Hirabayashi, Takashi Shinohara

  Jul. 2011, BIOLOGY OF REPRODUCTION, 85(1) (1), 208 - 217, English

  [Refereed]

  Scientific journal


• Muscle Fiber Type-Predominant Promoter Activity in Lentiviral-Mediated Transgenic Mouse

  Tomohiro Suga, En Kimura, Yuka Morioka, Masahito Ikawa, Sheng Li, Katsuhisa Uchino, Yuji Uchida, Satoshi Yamashita, Yasushi Maeda, Jeffrey S. Chamberlain, Makoto Uchino

  Mar. 2011, PLOS ONE, 6(3) (3), e16908, English

  [Refereed]

  Scientific journal


• Pravastatin induces placental growth factor (PGF) and ameliorates preeclampsia in a mouse model

  Keiichi Kumasawa, Masahito Ikawa, Hiroyasu Kidoya, Hidetoshi Hasuwa, Tomoko Saito-Fujita, Yuka Morioka, Nobuyuki Takakura, Tadashi Kimura, Masaru Okabe

  Jan. 2011, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 108(4) (4), 1451 - 1455, English

  [Refereed]

  Scientific journal


• Calponin 3 Regulates Actin Cytoskeleton Rearrangement in Trophoblastic Cell Fusion

  Yukinao Shibukawa, Natsuko Yamazaki, Keiichi Kumasawa, Etsuko Daimon, Michiko Tajiri, Yuka Okada, Masahito Ikawa, Yoshinao Wada

  Nov. 2010, MOLECULAR BIOLOGY OF THE CELL, 21(22) (22), 3973 - 3984, English

  [Refereed]

  Scientific journal


• Male Germline and Embryonic Stem Cell Lines from NOD Mice: Efficient Derivation of GS Cells from a Nonpermissive Strain for ES Cell Derivation

  Hiroshi Ohta, Yasuhide Ohinata, Masahito Ikawa, Yuka Morioka, Yuko Sakaide, Mitinori Saitou, Osami Kanagawa, Teruhiko Wakayama

  Dec. 2009, BIOLOGY OF REPRODUCTION, 81(6) (6), 1147 - 1153, English

  [Refereed]

  Scientific journal


• Placenta-Specific Gene Activation and Inactivation Using Integrase-Defective Lentiviral Vectors With the Cre/LoxP System

  Yuka Morioka, Ayako Isotani, Robert G. Oshima, Masaru Kabe, Masahito Ikawa

  Dec. 2009, GENESIS, 47(12) (12), 793 - 798, English

  [Refereed]

  Scientific journal


• Targeted Gene Modification in Mouse ES Cells Using Integrase-Defective Lentiviral Vectors

  Yuka Okada, Yuko Ueshin, Hidetoshi Hasuwa, Kazuhiro Takumi, Masaru Okabe, Masahito Ikawa

  Apr. 2009, GENESIS, 47(4) (4), 217 - 223, English

  [Refereed]

  Scientific journal


• Systemic administration of a PEGylated adenovirus vector with a cancer-specific promoter is effective in a mouse model of metastasis.

  Yao X, Yoshioka Y, Morishige T, Eto Y, Watanabe H, Okada Y, Mizuguchi H, Mukai Y, Okada N, Nakagawa S

  2009, Gene Ther., 2009 Dec;16(12):1395-404

  [Refereed]


• Development and evaluation of a novel placenta-specific gene manipulation method using lentiviral vectors

  Yuka Okada

  Jul. 2008, YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, 128(7) (7), 1007 - 1011, Japanese

  [Refereed]


• TERT promoter-driven adenovirus vector for cancer gene therapy via systemic injection

  Xinglei Yao, Yasuo Yoshioka, Yusuke Eto, Tomohiro Morishige, Yuka Okada, Hiroyuki Mizuguchi, Yohei Mukal, Naoki Okada, Shinsaku Nakagawa

  Oct. 2007, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 362(2) (2), 419 - 424, English

  [Refereed]

  Scientific journal


• Effective tumor targeted gene transfer using PEGylated adenovirus vector via systemic administration

  Jian-Qing Gao, Yusuke Eto, Yasuo Yoshioka, Fumiko Sekiguchi, Shinnosuke Kurachi, Tomohiro Morishige, Xinglei Yao, Hikaru Watanabe, Ratima Asavatanabodee, Fuminori Sakurai, Hiroyuki Mizuguchi, Yuka Okada, Yohei Mukai, Yasuo Tsutsumi, Tadanori Mayumi, Naoki Okada, Shinsaku Nakagawa

  Sep. 2007, JOURNAL OF CONTROLLED RELEASE, 122(1) (1), 102 - 110, English

  [Refereed]

  Scientific journal


• Complementation of placental defects and embryonic lethality by trophoblast-specific lentiviral gene transfer

  Yuka Okada, Yuko Ueshin, Ayako Isotani, Tomoko Saito-Fujita, Hisako Nakashima, Kazushi Kimura, Akira Mizoguchi, Masatsugu Oh-hora, Yoshiko Mori, Masato Ogata, Robert G. Oshima, Masaru Okabe, Masahito Ikawa

  Feb. 2007, NATURE BIOTECHNOLOGY, 25(2) (2), 233 - 237, English

  [Refereed]

  Scientific journal


• Tumor suppressive efficacy through augmentation of tumor-infiltrating immune cells by intratumoral injection of chemokine-expressing adenoviral vector

  N Okada, A Sasaki, M Niwa, Y Okada, Y Hatanaka, Y Tani, H Mizuguchi, S Nakagawa, T Fujita, A Yamamoto

  Apr. 2006, CANCER GENE THERAPY, 13(4) (4), 393 - 405, English

  Scientific journal


• Transcriptional targeting of RGD fiber-mutant adenovirus vectors can improve the safety of suicide gene therapy for murine melanoma

  Y Okada, N Okada, H Mizuguchi, T Hayakawa, S Nakagawa, T Mayumi

  Jul. 2005, CANCER GENE THERAPY, 12(7) (7), 608 - 616, English

  [Refereed]

  Scientific journal


• Augmentation of the migratory ability of DC-based vaccine into regional lymph nodes by efficient CCR7 gene transduction

  N Okada, N Mori, R Koretomo, Y Okada, T Nakayama, O Yoshie, H Mizuguchi, T Hayakawa, S Nakagawa, T Mayumi, T Fujita, A Yamamoto

  Jan. 2005, GENE THERAPY, 12(2) (2), 129 - 139, English

  Scientific journal


• Immunological properties and vaccine efficacy of murine dendritic cells simultaneously expressing melanoma-associated antigen and interleukin-12

  N Okada, S Iiyama, Y Okada, H Mizuguchi, T Hayakawa, S Nakagawa, T Mayumi, T Fujita, A Yamamoto

  Jan. 2005, CANCER GENE THERAPY, 12(1) (1), 72 - 83, English

  [Refereed]

  Scientific journal


• Anti-tumor activity of chemokine is affected by both kinds of tumors and the activation state of the host's immune system: implications for chemokine-based cancer immunotherapy

  N Okada, JQ Gao, A Sasaki, M Niwa, Y Okada, T Nakayama, O Yoshie, H Mizuguchi, T Hayakawa, T Fujita, A Yamamoto, Y Tsutsumi, T Mayumi, S Nakagawa

  Apr. 2004, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 317(1) (1), 68 - 76, English

  Scientific journal


• Anti-tumor activity of chemokine is affected by both kinds of tumors and the activation state of the host's immune system: implications for chemokine-based cancer immunotherapy

  N Okada, JQ Gao, A Sasaki, M Niwa, Y Okada, T Nakayama, O Yoshie, H Mizuguchi, T Hayakawa, T Fujita, A Yamamoto, Y Tsutsumi, T Mayumi, S Nakagawa

  Apr. 2004, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 317(1) (1), 68 - 76, English

  [Refereed]

  Scientific journal


• Optimization of antitumor efficacy and safety of in vivo cytokine gene therapy using RGD fiber-mutant adenovirus vector for preexisting murine melanoma.

  Yuka Okada, Naoki Okada, Hiroyuki Mizuguchi, Koichi Takahashi, Takao Hayakawa, Tadanori Mayumi, Nobuyasu Mizuno

  We previously reported that RGD fiber-mutant adenovirus vector (AdRGD) was a very useful vector system for in vivo cytokine gene therapy for established murine B16BL6 melanoma. However, intratumoral administration of AdRGD expressing tumor necrosis factor alpha (AdRGD-TNFalpha) at high dose revealed not only the dramatic reinforcement of anti-tumor effect but also serious adverse effects, such as body weight reduction and sudden death, caused by high-level TNF-alpha leakage from the tumor into circulation. These results strongly suggested that the determination of 'limiting dose', which demonstrated therapeutic effectiveness without adverse effect, against each vector was important for the development of appropriate cytokine gene therapy. In the present study, we investigated the efficacy and the safety of AdRGD expressing interleukin-12 (AdRGD-IL12) in murine melanoma model, and determined its limiting dose. Moreover, we demonstrated that combination therapy using AdRGD-IL12 and AdRGD-TNFalpha at limiting doses or less could achieve more effective tumor regression without adverse effects. Therefore, we conclude that a combination of multiple AdRGD expressing cytokines having distinct anti-tumor mechanisms can contribute to the establishment of in vivo cytokine gene therapy for melanoma, which possesses both excellent efficacy and high safety.

  3, Feb. 2004, Biochimica et biophysica acta, 1670(3) (3), 172 - 80, English, International magazine

  [Refereed]


• Dendritic cells transduced with gp100 gene by RGD fiber-mutant adenovirus vectors are highly efficacious in generating anti-B16BL6 melanoma immunity in mice

  N Okada, Y Masunaga, Y Okada, H Mizuguchi, S Iiyama, N Mori, A Sasaki, S Nakagawa, T Mayumi, T Hayakawa, T Fujita, A Yamamoto

  Oct. 2003, GENE THERAPY, 10(22) (22), 1891 - 1902, English

  Scientific journal


• Gene transduction efficiency and maturation status in mouse bone marrow-derived dendritic cells infected with conventional or RGD fiber-mutant adenovirus vectors

  N Okada, Y Masunaga, Y Okada, S Iiyama, N Mori, T Tsuda, A Matsubara, H Mizuguchi, T Hayakawa, T Fujita, A Yamamoto

  May 2003, CANCER GENE THERAPY, 10(5) (5), 421 - 431, English

  [Refereed]

  Scientific journal


• An investigation of adverse effects caused by the injection of high-dose TNF alpha-expressing adenovirus vector into established murine melanoma

  Y Okada, N Okada, H Mizuguchi, T Hayakawa, T Mayumi, N Mizuno

  Apr. 2003, GENE THERAPY, 10(8) (8), 700 - 705, English

  Scientific journal


• Tumor necrosis factor alpha-gene therapy for an established murine melanoma using RGD (Arg-Gly-Asp) fiber-mutant adenovirus vectors

  Y Okada, N Okada, S Nakagawa, H Mizuguchi, K Takahashi, N Mizuno, T Fujita, A Yamamoto, T Hayakawa, T Mayumi

  Apr. 2002, JAPANESE JOURNAL OF CANCER RESEARCH, 93(4) (4), 436 - 444, English

  [Refereed]

  Scientific journal


• Fiber-mutant technique can augment gene transduction efficacy and anti-tumor effects against established murine melanoma by cytokine-gene therapy using adenovirus vectors

  Y Okada, N Okada, S Nakagawa, H Mizuguchi, M Kanehira, N Nishino, K Takahashi, N Mizuno, T Hayakawa, T Mayumi

  Mar. 2002, CANCER LETTERS, 177(1) (1), 57 - 63, English

  [Refereed]

  Scientific journal


• Efficient antigen gene transduction using Arg-Gly-Asp fiber-mutant adenovirus vectors can potentiate antitumor vaccine efficacy and maturation of murine dendritic cells

  N Okada, T Saito, Y Masunaga, Y Tsukada, S Nakagawa, H Mizuguchi, K Mori, Y Okada, T Fujita, T Hayakawa, T Mayumi, A Yamamoto

  Nov. 2001, CANCER RESEARCH, 61(21) (21), 7913 - 7919, English

  Scientific journal


• Cytoplasmic gene expression system enhances the efficiency of cationic liposome-mediated in vivo gene transfer into mouse brain

  H Mizuguchi, T Nakagawa, Y Morioka, S Imazu, M Nakanishi, T Kondo, T Hayakawa, T Mayumi

  May 1997, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 234(1) (1), 15 - 18, English

  Scientific journal


• 固形癌遺伝子治療に対する新しい戦略 腫瘍支配動脈内へのTNF-α遺伝子導入による抗腫瘍効果の誘導

  中川 哲彦, 水口 裕之, 今津 進, 森岡 裕香, 中川 晋作, 真弓 忠範, 中西 真人

  (公社)日本薬学会, Mar. 1996, 日本薬学会年会要旨集, 116年会(4) (4), 78 - 78, Japanese

• Muscle fiber type-predominant promoter activity in lentiviral-mediated transgenic mouse

  T. Suga, E. Kimura, Y. Morioka, M. Ikawa, K. Uchino, T. Koide, Y. Uchida, S. Yamashita, Y. Maeda, S. Li, J. S. Chamberlain, M. Uchino

  Oct. 2010, HUMAN GENE THERAPY, 21(10) (10), 1469 - 1469, English

  Summary international conference


• Transductional and transcriptional tumor-targeting using adenoviral vector with PEGylation and TERT promoter on systemic administration into tumor-bearing mice

  Yusuke Eto, Shinnosuke Kurachi, Tomohiro Morishige, Xinglei Yao, Hikaru Watanabe, Yuka Okada, Hiroyuki Mizuguchi, Yasuo Tsutsumi, Naoki Okada, Shinsaku Nakagawa

  Apr. 2006, CANCER RESEARCH, 66(8) (8), English

  Summary international conference


• Erratum: Fiber-mutant technique can augment gene transduction efficacy and anti-tumor effects against established murine melanoma by cytokine-gene therapy using adenovirus vectors (Cancer Letters (2002) 177 (57-63))

  Yuka Okada, Naoki Okada, Shinsaku Nakagawa, Hiroyuki Mizuguchi, Makiko Kanehira, Naoko Nishino, Koichi Takahashi, Nobuyasu Mizuno, Takao Hayakawa, Tadanori Mayumi

  10 Feb. 2004, Cancer Letters, 204, 115 - 116


• Optimization of antitumor efficacy and safety of in vivo cytokine gene therapy using RGD fiber-mutant adenovirus vector for preexisting murine melanoma

  Y Okada, N Okada, H Mizuguchi, K Takahashi, T Hayakawa, T Mayumi, N Mizuno

  Feb. 2004, BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 1670(3) (3), 172 - 180, English


• New strategy for solid cancer gene therapy. Induction of anti-tumor effect by TNF-.ALPHA. gene transfer into tumor control artery.

  中川哲彦, 水口裕之, 今津進, 森岡裕香, 中川晋作, 真弓忠範, 中西真人

  (公社)日本薬学会, Mar. 1996, 日本薬学会年会要旨集, 116th(Pt 4) (Pt 4), 78 - 78, Japanese

• JAPANESE ASSOCIATION FOR LABORATORY ANIMAL SCIENCE


• THE MOLECULAR BIOLOGY SOCIETY OF JAPAN


• 日本生殖免疫学会


• 日本癌学会

• 異種間キメラ動体内で多能性幹細胞由来の子宮を作る研究

  磯谷 綾子, 森岡 裕香, 本多 新, 由利 俊祐

  日本学術振興会, 科学研究費助成事業, 基盤研究(B), 奈良先端科学技術大学院大学, 01 Apr. 2024 - 31 Mar. 2028


• 独自に見出した新規因子が関わる母児間鉄代謝制御機構の解明

  森岡 裕香

  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, 01 Apr. 2023 - 31 Mar. 2026

  
  先行研究において、独自に作製した遺伝子X欠損マウスでは、胎盤と胎仔肝において鉄代謝関連遺伝子Hampの発現が上昇するとともに、胎仔肝に鉄の蓄積が生じることを明らかにし、Xが母児間鉄代謝に関わる新規因子である可能性を見出した。Xの肝臓における発現や鉄代謝への関与は報告されていないが、qPCR解析により胎齢18.5日目の胎仔肝において発現していることが確認された。 そこで、X欠損胎仔肝におけるHamp発現上昇が、他臓器の表現型に起因する二次的な変化であるのか、それとも肝細胞に対する直接的な作用によるものかについて、培養細胞を用いた検証を計画したが、既存の培養肝細胞株ではいずれもX発現が検出できず、解析に使用できなかった。より生体内を反映した細胞を得るために、胎仔肝から初代培養を試みたが、安定的な維持が難しく、また、Xの発現も確認できなかった。今後は、in vivoでの検証が可能な新しい解析モデルの確立に研究計画を修正し、さらなる検討を進める予定である。


• ロイシンセンシングによる腫瘍発生機序の解明と予防法の開発

  星 奈美子, 森岡 裕香

  日本学術振興会, 科学研究費助成事業, 挑戦的研究(萌芽), 神戸大学, 30 Jun. 2023 - 31 Mar. 2025


• 母児間鉄代謝に関わる新規因子の解明

  森岡 裕香

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, Apr. 2020 - Mar. 2023

  ①遺伝子欠損が胎仔肝に与える影響の解析 ： 先行研究により、独自に作製したノックアウトマウスの胎盤では、同腹に存在する野生型マウスの胎盤と比較して、鉄代謝遺伝子の発現が亢進していることを見出した。本年度は、胎仔肝についても解析を行った結果、胎盤と同様に野生型よりもノックアウトの方が、鉄代謝遺伝子の発現が高いことが確認された。妊娠マウスの血中鉄濃度が母体の肝臓のみならず胎盤の鉄代謝因子にも影響を与えることが知られているが、ノックアウト、野生型とも同じ母体血にさらされているため、この発現亢進には遺伝子欠損が直接起因している可能性が示唆された。
  ②母体血中鉄濃度の変化が胎盤・胎仔肝の鉄代謝遺伝子発現に与える影響の解析 ： 「遺伝子を欠損した胎盤でも、母体血中鉄濃度の変化に正しく応答できるのか？」を調べるため、ノックアウトと野生型の仔を妊娠した母マウスに、鉄欠乏または鉄過剰といった鉄調整食を与えて母体血中鉄濃度を変化させた際の、胎盤・胎仔肝の鉄代謝遺伝子発現を解析した。交配の1週間前から全妊娠期間にわたって鉄調整食を与えた結果、胎盤・胎仔肝における鉄代謝遺伝子の発現変動が認められたが、ノックアウト、野生型のいずれも同様の増加・減少パターンを示し、遺伝子を欠損しても母体血中鉄濃度変化に対する反応性は維持されていることが明らかになった。これは、昨年度に得られた、培養胎盤細胞を用いて行った解析の結果とも一致する知見である。


• Analysis of PKX-deficient mice that indicate placental disorder.

  MORIOKA YUKA

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Apr. 2017 - Mar. 2020

  In this study, we confirmed that PKX deficiency resulted in activation of AKT in differentiated trophoblast stem cells (day6-TSC). AKT is known to be comprised three highly homologous isoforms: AKT1, AKT2, and AKT3. All three AKT isoforms were expressed in day6-TSC with almost equivalent levels between wild-type and PKX-null genotypes. However, upregulation of phosphorylation was observed in all three AKT isoforms derived from PKX-null cells compared with wild-type cells. Because PKX deficiency did not influence expression and the activity of the factors which have been already known as a regulation factor of AKT, it was suggested that PKX regulate AKT phosphorylation through unknown mechanism.


• Molecular targets to suppress microenvironment changes and invasive cancer recurrence after radiotherapy

  Nam JinMin, ONODERA Yasuhito

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Hokkaido University, Apr. 2016 - Mar. 2019

  Integrins regulation and microenvironment changes are involved in cancer cell survival, invasion and metastasis. Radiation can remodel the microenvironment by secreted molecules which contribute to radioresistance and enhancing invasive activity in cancer cells. In this study, we focused on microenvironment after radiation treatment, and analyzed molecular mechanisms of invasive recurrence after radiotherapy. We found that intergrin-binding radiation sensitizer decreased cancer cell survival and invasive activity after radiation in breast cancer cells. In addition, our data suggest that lysosomes function and trafficking are involved in invasive activity after radiation treatment.


• Analysis of a novel protein kinase-deficient mice that indicate perinatal disorders.

  Morioka Yuka

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, Apr. 2015 - Mar. 2017

  Nrk is a Ser/Thr kinase and our recent study using Nrk-deficient mice suggested the importance of Nrk in perinatal period including placental development. We demonstrated that differentiated trophoblasts from murine embryonic stem cells endogenously expressed Nrk and that Nrk disruption led to the enhanced proliferation of differentiated trophoblasts. Furthermore, we demonstrated that AKT phosphorylation was upregulated in Nrk-null trophoblasts and that inhibition of AKT phosphorylation cancelled the enhanced proliferation observed in differentiated Nrk-null trophoblasts. These results indicated that the upregulation of AKT phosphorylation was the possible cause of enhanced proliferation observed in Nrk-null trophoblasts. The upregulation of AKT phosphorylation was also confirmed in enlarged Nrk-null placentas in vivo, suggesting that proper regulation of AKT by Nrk was important for normal placental development.


• A search and functional analysis of novel placenta-related genes to overcome recurrent miscarriage.

  MORIOKA YUKA

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Hokkaido University, 2012 - 2014, Principal investigator

  In this study, we searched for novel placenta-related genes from the comprehensive analysis by the microarray using our original cultured cells followed by functional analysis. We obtained eight candidate genes, and two of those showed following interesting phenotypes in mice. The placenta-specific overexpression of candidate gene A caused placental disorder and intrauterine growth retardation. The candidate gene B deficient mice showed multiple abnormalities, placental overgrowth, abnormal delivery and neonatal anemia in the perinatal period. It is expected that these mice are useful as a new recurrent miscarriage model.

  Competitive research funding


• Development and analysis of a novel preeclampsia model using a placenta-specific gene manipulation method.

  MORIOKA Yuka

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Young Scientists (B), Hokkaido University, 2010 - 2011, Principal investigator

  Previously, we established a placenta-specific gene manipulation method. Applying this technology, we expressed soluble VEGF receptor 1(sFLT1) known as an anti-angiogenic factor, specifically in the murine placenta. The mice showed hypertension and proteinuria during pregnancy. These are similar symptoms of human preeclampsia patients. We further showed that pravastatin induced the VEGF-like angiogenic factor placental growth factor(PGF) and ameliorated the symptoms.

  Competitive research funding


• レンチウイルスベクターを利用した胎盤特異的な遺伝子操作法の開発とその応用

  岡田裕香

  文部科学省, 科学研究費補助金(若手研究(B)), 若手研究(B), 大阪大学, 2007 - 2008

  本年度は、マウス個体における胎盤特異的な遺伝子操作技術を確立し、それを応用して胎盤における遺伝子機能の制御を試みるとともに、新規胎盤機能遺伝子の探索に着手した。まず、レポーター遺伝子としてEGFPを搭載したレンチウイルス(LV)ベクターを用いて検討を行った結果、酸性タイロード処理により透明帯を除去しだ胚盤胞を、カプシドタンパクp24濃度1μg/mlのLVベクター溶液中で4〜5時間培養した後、偽妊娠マウスに移植することで、胚の発生率に影響を与えることなく、100%の効率で胎盤特異的に遺伝子導入できることが明らかとなった。EGFPの発現は胎盤全体に観察され、FISH解析の結果、1細胞あたり平均6.6コピーの遺伝子が導入されていた。さらに、この技術の応用として、胎盤異常が原因で胎生10.5日目までに致死となるp38α欠損マウスの胚盤胞にp38aを発現するLVベクターを感染させ、胎盤特異的に欠損している遺伝子を補ったところ、胎盤の構造や機能が回復し、胎児の発生が正常にサポートされた。この結果は、胎生致死マウスの生後解析が可能になる事を示しており、個体レベルでの遺伝子機能解析に大きく貢献できると考えられる。さらに、p38α欠損マウスの胎盤にアイソフォームであるp38βの遺伝子を導入した場合にも同様にノックアウト個体が誕生したことから、「胎盤においてp38βはp38αの機能を相補できる」...

  Competitive research funding


• 腫瘍組織標的化アデノウイルスベクターの創製と癌遺伝子治療への応用

  岡田裕香

  文部科学省, 科学研究費補助金(若手研究(B)), 若手研究(B), 大阪大学, 2005 - 2006

  前年度の検討により、腫瘍特異的プロモーターを搭載したアデノウイルスベクター(Ad)は、有効性と安全性に優れた癌遺伝子治療用ベクターとして有用であることが示された。本年度は、これらを全身性投与可能なベクターに発展させるため、さらなる改良を試みた。まず、TERTプロモーターまたはCMVプロモーターの制御下にレポーター遺伝子を発現するAdのキャプシドを、ポリエチレングリコール(PEG)で修飾(PEG分子量5,000、修飾率95%)したPEG-Ad-TERT/Luc、PEG-Ad-CMV/Lucを構築し、腹部担癌マウスに尾静脈内投与した際のベクター粒子分布および遺伝子発現分布を解析した。その結果、ベクター粒子の分布はプロモーター改変の影響を受けずほぼ同様のパターンを示し、いずれにおいても血中滞留性の向上や腫瘍への集積性が確認された。一方、遺伝子発現については、標的組織である腫瘍における発現と、副作用の主因となる肝臓での発現の比を算出したところ、PEG-Ad-TERT/LucはPEG-Ad-CMV/Lucと比較して、最大10,000倍も高値を示し、標的外の組織では、たとえ感染しても遺伝子発現が抑えられることが判明した。このことから、PEG-Ad-TERTは、PEG修飾による体内動態制御と、プロモーター改変による遺伝子発現制御の両面から腫瘍選択性を増強されており、全身投与型ベクターとして...

  Competitive research funding


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  Competitive research funding


• 非分裂細胞を標的とした遺伝子治療における細胞質内遺伝子発現系の最適化

  岡田 裕香

  日本科学協会, 平成13年度笹川科学研究助成

  Competitive research funding


• メラノーマ遺伝子治療に最適化した改変型アデノウイルスベクターの創製

  岡田 裕香

  日本科学協会, 平成16年度笹川科学研究助成

  Competitive research funding


• BTLAを標的とした新規癌免疫療法の開発

  岡田 裕香

  上原記念生命科学財団, 平成20年度海外留学助成金リサーチフェローシップ

  Competitive research funding


• 生殖補助医療の向上を目指した新規着床・胎盤形成関連因子の探索

  森岡 裕香

  神澤医学研究振興財団, 平成22年度研究助成, Principal investigator

  Competitive research funding


• piggyBacトランスポゾンを利用した標的部位特異的なゲノム改変技術の開発

  森岡 裕香

  倉田記念日立科学技術財団, 平成22年度倉田奨励金, Principal investigator

  Competitive research funding


• X染色体上に存在する新規胎盤関連遺伝子の探索と機能解析

  森岡 裕香

  武田科学振興財団, 2011年度医学系研究奨励（基礎）, Principal investigator

  Competitive research funding


• 理想的な疾患モデル作製に向けたゲノム改変技術の開発

  森岡 裕香

  アステラス病態代謝研究会, 平成23年度（第43回）公益財団法人アステラス病態代謝研究会研究助成金, Principal investigator

  Competitive research funding


• レンチウイルスベクターを利用したin vivoダイレクトジーントラップシステムの開発

  森岡 裕香

  倉田記念日立科学技術財団, 平成23年度倉田奨励金, Principal investigator

  Competitive research funding


• 分娩異常マウスの解析と診断・治療法開発への応用

  森岡 裕香

  金原一郎記念医学医療振興財団, 第28回基礎医学医療研究助成金, Principal investigator

  Competitive research funding


• 独自のモデルマウスを利用した分娩異常メカニズムの解明と診断・治療法開発への応用

  森岡 裕香

  稲盛財団, 2014年度稲盛財団研究助成, Principal investigator

  Competitive research funding


• 遺伝子改変マウスを利用した周産期障害発症メカニズムの解明と診断・治療法開発への応用

  森岡 裕香

  武田科学振興財団, 2016年度医学系研究奨励（基礎）, Principal investigator

  Competitive research funding