2023 Fiscal Year Annual Research Report
Project/Area Number |
23H02980
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Allocation Type | Single-year Grants |
Research Institution | Osaka University |
Principal Investigator |
奥崎 大介 大阪大学, 免疫学フロンティア研究センター, 特任准教授(常勤) (00346131)
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Co-Investigator(Kenkyū-buntansha) |
山本 浩文 大阪大学, 大学院医学系研究科, 教授 (30322184)
横山 雄起 大阪大学, 大学院医学系研究科, 助教 (60615714)
森 正樹 東海大学, 医学部, 特任教授 (70190999)
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Project Period (FY) |
2023-04-01 – 2026-03-31
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Keywords | 癌幹細胞 / 癌精巣抗原 |
Outline of Annual Research Achievements |
日本人の死因の第1位は癌である。その中でも大腸癌は、高齢化や食生活の欧米化等により増加傾向にある。本邦における大腸癌の死亡率は男性で第3位、女性で第1位であり、転移や再発を起こすと治療が困難な状況であるため、さらなる対策が急務である。近年、固形癌においても自己複製能と多分化能を有し、半永久的に子孫細胞を作り続けるごく少数の癌幹細胞という概念が注目されている。癌の起点となる癌幹細胞は治療抵抗性であり、癌の根治のためにはCSCの駆除が必要であるが、未だ有効な治療法は実現されていない。本研究では、我々がこれまで開発してきた癌幹細胞遺伝子検出のための複数の実験ツールを利用し、それぞれの癌細胞のRNAseqやシングルセル解析データを比較して、共通項を見出すことで新規の癌幹細胞マーカーを見出すことを目的とした。更に正常組織では精巣以外には発現のない癌精巣抗原 (CTA:Cancer testis antigen) との合致性にも注目して、副作用のない癌幹細胞治療標的分子の同定をめざす。2023年度はCT83はODC-degron導入により作製したCSC細胞株においても高発現しており、かつCTA でもあるCT83遺伝子に着目した。CT83は正常組織では男性において主に微小管構成するチューブリンの制御を介して精子を形成する役割をもち、精巣以外の正常組織では発現がみられない。CT83が乳癌で未だ有効な治療法が確立されていないTNBC (Triple Negative Breast Cancer)細胞株において顕著な発現亢進を示すことから、CT83の乳癌におけるCSCとの関連性について解析を進めている。
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Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
各種解析結果とCTA databaseとの照合によりCSC関連分子候補としてCT83遺伝子に着目し, TNBCでの癌幹細胞性との関わりにおいて有意な結果を得つつある。他方、臨床サンプルとの整合性を担保しつつ、SOX2発現可視化マウスを利用した遺伝子候補から3個のCSC関連遺伝子候補が、ODC degron 導入細胞からも4個のCSC関連遺伝子候補が浮かび上がってきた。
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Strategy for Future Research Activity |
CT83の幹細胞性への寄与を証明すべく、過剰発現、ノックダウンによって、スフェロイド形成能、活性酸素種(ROS)産生、抗癌剤抵抗性、造腫瘍性などについて検討する。新規CSC関連遺伝子についても順次遺伝子発現クローンを作製し、癌細胞性について検証を進めてゆく。
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Research Products
(50 results)
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[Journal Article] d-Alanine Affects the Circadian Clock to Regulate Glucose Metabolism in the Kidney2023
Author(s)
Sakai S, Tanaka Y, Tsukamoto Y, Kimura-Ohba S, Hesaka A, Hamase K, Hsieh CL, Kawakami E, Ono H, Yokote K, Yoshino M, Okuzaki D, Matsumura H, Fukushima A, Mita M, Nakane M, Doi M, Isaka Y, Kimura T.
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Journal Title
Kidney360
Volume: 5
Pages: 237~251
DOI
Peer Reviewed / Open Access
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[Journal Article] Resting phase-administration of lemborexant ameliorates sleep and glucose tolerance in type 2 diabetic mice2023
Author(s)
Tsuneki H, Sugiyama M, Sato K, Ito H, Nagai S, Kon K, Wada T, Kobayashi N, Okada T, Toyooka N, Kawasaki M, Ito T, Otsubo R, Okuzaki D, Yasui T, Sasaoka T.
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Journal Title
European Journal of Pharmacology
Volume: 961
Pages: 176190~176190
DOI
Peer Reviewed / Open Access
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[Journal Article] Dengue virus infection induces selective expansion of Vγ4 and Vγ6TCR γδ T cells in the small intestine and a cytokine storm driving vascular leakage in mice2023
Author(s)
Kurosu T, Okuzaki D, Sakai Y, Kadi MA, Phanthanawiboon S, Ami Y, Shimojima M, Yoshikawa T, Fukushi S, Nagata N, Suzuki T, Kamimura D, Murakami M, Ebihara H, Saijo M.
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Journal Title
PLOS Neglected Tropical Diseases
Volume: 17
Pages: 11743~11743
DOI
Peer Reviewed / Open Access
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[Journal Article] Opposing roles of RUBCN isoforms in autophagy and memory B cell generation2023
Author(s)
Tsai CY, Sakakibara S, Kuan YD, Omori H, El Hussien MA, Okuzaki D, Lu SL, Noda T, Tabata K, Nakamura S, Yoshimori T, Kikutani H.
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Journal Title
Science Signaling
Volume: 16
Pages: -
DOI
Peer Reviewed
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[Journal Article] Single-cell transcriptomics of human cholesteatoma identifies an activin A-producing osteoclastogenic fibroblast subset inducing bone destruction2023
Author(s)
Shimizu K, Kikuta J, Ohta Y, Uchida Y, Miyamoto Y, Morimoto A, Yari S, Sato T, Kamakura T, Oshima K, Imai R, Liu YC, Okuzaki D, Hara T, Motooka D, Emoto N, Inohara H, Ishii M.
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Journal Title
Nature Communications
Volume: 14
Pages: -
DOI
Peer Reviewed / Open Access
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[Journal Article] Combination of HBA1, TTR, and SERPINF2 in plasma defines phenotype correlated with severe burn outcome2023
Author(s)
Onishi S, Matsumoto H, Sugihara F, Ebihara T, Matsuura H, Osuka A, Okuzaki D, Ogura H, Oda J.
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Journal Title
iScience
Volume: 26
Pages: 107271~107271
DOI
Peer Reviewed / Open Access
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[Journal Article] Wnt5a-YAP signaling axis mediates mechanotransduction in cardiac myocytes and contributes to contractile dysfunction induced by pressure overload2023
Author(s)
Kishimoto H, Iwasaki M, Wada K, Horitani K, Tsukamoto O, Kamikubo K, Nomura S, Matsumoto S, Harada T, Motooka D, Okuzaki D, Takashima S, Komuro I, Kikuchi A, Shiojima I.
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Journal Title
iScience
Volume: 26
Pages: 107146~107146
DOI
Peer Reviewed / Open Access
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[Journal Article] Sialylation shapes mucus architecture inhibiting bacterial invasion in the colon2023
Author(s)
Taniguchi M, Okumura R, Matsuzaki T, Nakatani A, Sakaki K, Okamoto S, Ishibashi A, Tani H, Horikiri M, Kobayashi N, Yoshikawa HY, Motooka D, Okuzaki D, Nakamura S, Kida T, Kameyama A, Takeda K.
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Journal Title
Mucosal Immunology
Volume: 16
Pages: 624~641
DOI
Peer Reviewed / Open Access
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[Journal Article] COVID-19 relapse associated with SARS-CoV-2 evasion from CD4+ T-cell recognition in an agammaglobulinemia patient2023
Author(s)
Morita R, Kubota-Koketsu R, Lu X, Sasaki T, Nakayama EE, Liu YC, Okuzaki D, Motooka D, Wing JB, Fujikawa Y, Ichida Y, Amo K, Goto T, Hara J, Shirano M, Yamasaki S, Shioda T.
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Journal Title
iScience
Volume: 26
Pages: 106685~106685
DOI
Peer Reviewed / Open Access
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[Journal Article] Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity2023
Author(s)
Edahiro R, Shirai Y, Takeshima Y, Sakakibara S, Yamaguchi Y, Murakami T, Morita T, Kato Y, Liu YC, Motooka D, Naito Y, Takuwa A, Sugihara F, Tanaka K, Wing JB, Sonehara K, Tomofuji Y; Japan COVID-19 Task Force; Namkoong H, Tanaka H, Lee H, Fukunaga K, Hirata H, Takeda Y, Okuzaki D, Kumanogoh A, Okada Y.
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Journal Title
Nature Genetics
Volume: 55
Pages: 753~767
DOI
Peer Reviewed / Open Access
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[Journal Article] Tumor-suppressive role of the musculoaponeurotic fibrosarcoma gene in colorectal cancer2023
Author(s)
Itakura H, Hata T, Okuzaki D, Takeda K, Iso K, Qian Y, Morimoto Y, Adachi T, Hirose H, Yokoyama Y, Ogino T, Miyoshi N, Takahashi H, Uemura M, Mizushima T, Hinoi T, Mori M, Doki Y, Eguchi H, Yamamoto H.
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Journal Title
iScience
Volume: 26
Pages: 106478~106478
DOI
Peer Reviewed / Open Access
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[Journal Article] Circulating miR-20b-5p and miR-330-3p are novel biomarkers for progression of atrial fibrillation: Intracardiac/extracardiac plasma sample analysis by small RNA sequencing2023
Author(s)
Harada M, Okuzaki D, Yamauchi A, Ishikawa S, Nomura Y, Nishimura A, Motoike Y, Koshikawa M, Hitachi K, Tsuchida K, Amano K, Maekawa A, Takagi Y, Watanabe E, Ozaki Y, Izawa H.
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Journal Title
PLOS ONE
Volume: 18
Pages: 283942~283942
DOI
Peer Reviewed / Open Access
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[Journal Article] Celastrol suppresses humoral immune responses and autoimmunity by targeting the COMMD3/8 complex2023
Author(s)
Shirai T, Nakai A, Ando E, Fujimoto J, Leach S, Arimori T, Higo D, van Eerden FJ, Tulyeu J, Liu YC, Okuzaki D, Murayama MA, Miyata H, Nunomura K, Lin B, Tani A, Kumanogoh A, Ikawa M, Wing JB, Standley DM, Takagi J, Suzuki K.
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Journal Title
Science Immunology
Volume: 8
Pages: -
DOI
Peer Reviewed
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[Journal Article] ONO-1301 enhances post-transplantation survival of human induced pluripotent stem cell-derived cardiac tissue sheet by promoting angiogenesis2023
Author(s)
Qu X, Li J, Liu L, Zhang J, Hua Y, Suzuki K, Harada A, Ishida M, Yoshida N, Okuzaki D, Sakai Y, Sawa Y, Miyagawa S.
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Journal Title
The Journal of Heart and Lung Transplantation
Volume: 42
Pages: 716~729
DOI
Peer Reviewed
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[Journal Article] Single-cell RNA-seq analysis identifies distinct myeloid cells in a case with encephalitis temporally associated with COVID-19 vaccination2023
Author(s)
Ishikawa M, Shimada Y, Ozono T, Matsumoto H, Ogura H, Kihara K, Mochizuki H, Okuno T, Sakakibara S, Kinoshita M, Okuzaki D.
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Journal Title
Frontiers in Immunology
Volume: 14
Pages: -
DOI
Peer Reviewed
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[Journal Article] Cancer-specific tissue-resident memory T-cells express ZNF683 in colorectal cancer2023
Author(s)
Kitakaze M, Uemura M, Hara T, Chijimatsu R, Motooka D, Hirai T, Konno M, Okuzaki D, Sekido Y, Hata T, Ogino T, Takahashi H, Miyoshi N, Ofusa K, Mizushima T, Eguchi H, Doki Y, Ishii H.
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Journal Title
British Journal of Cancer
Volume: 128
Pages: 1828~1837
DOI
Peer Reviewed / Open Access
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[Journal Article] Correction: Multiple knockout mouse and embryonic stem cell models reveal the role of miR-124a in neuronal maturation2023
Author(s)
Chaya T, Maeda Y, Sugimura R, Okuzaki D, Watanabe S, Varner LR, Motooka D, Gyoten D, Yamamoto H, Kato H, Furukawa T.
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Journal Title
Journal of Biological Chemistry
Volume: 299
Pages: 103066~103066
DOI
Peer Reviewed / Open Access
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[Journal Article] Ovarian high-grade serous carcinoma cells with low SMARCA4 expression and high SMARCA2 expression contribute to platinum resistance2023
Author(s)
Kido K, Nojima S, Motooka D, Nomura Y, Kohara M, Sato K, Ohshima K, Tahara S, Kurashige M, Umeda D, Takashima T, Kiyokawa H, Ukon K, Matsui T, Okuzaki D, Morii E.
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Journal Title
The Journal of Pathology
Volume: 260
Pages: 56~70
DOI
Peer Reviewed
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[Journal Article] XCR1+ conventional dendritic cell-induced CD4+ T helper 1 cell activation exacerbates cardiac remodeling after ischemic myocardial injury2023
Author(s)
Inui H, Nishida M, Ichii M, Nakaoka H, Asaji M, Ide S, Saito S, Saga A, Omatsu T, Tanaka K, Kanno K, Chang J, Zhu Y, Okada T, Okuzaki D, Matsui T, Ohama T, Koseki M, Morii E, Hosen N, Yamashita S, Sakata Y.
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Journal Title
Journal of Molecular and Cellular Cardiology
Volume: 176
Pages: 68~83
DOI
Peer Reviewed / Open Access
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[Journal Article] In vivo induction of activin A-producing alveolar macrophages supports the progression of lung cell carcinoma2023
Author(s)
Taniguchi S, Matsui T, Kimura K, Funaki S, Miyamoto Y, Uchida Y, Sudo T, Kikuta J, Hara T, Motooka D, Liu YC, Okuzaki D, Morii E, Emoto N, Shintani Y, Ishii M.
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Journal Title
Nature Communications
Volume: 14
Pages: -
DOI
Peer Reviewed / Open Access
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[Journal Article] Identification of a unique subset of tissue-resident memory CD4+ T cells in Crohn's disease2023
Author(s)
Yokoi T, Murakami M, Kihara T, Seno S, Arase M, Wing JB, Sondergaard JN, Kuwahara R, Minagawa T, Oguro-Igashira E, Motooka D, Okuzaki D, Mori R, Ikeda A, Sekido Y, Amano T, Iijima H, Ozono K, Mizushima T, Hirota S, Ikeuchi H, Takeda K.
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Journal Title
Proceedings of the National Academy of Sciences
Volume: 120
Pages: -
DOI
Peer Reviewed / Open Access
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[Journal Article] Stimulation of interferon-β responses by aberrant SARS-CoV-2 small viral RNAs acting as retinoic acid-inducible gene-I agonists2023
Author(s)
Arai Y, Yamanaka I, Okamoto T, Isobe A, Nakai N, Kamimura N, Suzuki T, Daidoji T, Ono T, Nakaya T, Matsumoto K, Okuzaki D, Watanabe Y.
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Journal Title
iScience
Volume: 26
Pages: 105742~105742
DOI
Peer Reviewed / Open Access
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[Journal Article] Peripheral‐dominant liver fibrosis and tumor distribution in a mouse model of congestive hepatopathy2023
Author(s)
Kawai H, Osawa Y, Tsunoda T, Matsuda M, Okawara M, Sakamoto Y, Shimagaki T, Tsutsui Y, Yoshida Y, Yoshikawa S, Doi H, Mori T, Yamazoe T, Yoshio S, Okamura T, Sugiyama M, Okuzaki D, Komatsu H, Inui A, Yanaga K, Ikegami T, Kanto T.
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Journal Title
Hepatology Research
Volume: 53
Pages: 370~376
DOI
Peer Reviewed
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[Journal Article] Combination of WFDC2, CHI3L1, and KRT19 in Plasma Defines a Clinically Useful Molecular Phenotype Associated with Prognosis in Critically Ill COVID-19 Patients2023
Author(s)
Ebihara T, Matsubara T, Togami Y, Matsumoto H, Tachino J, Matsuura H, Kojima T, Sugihara F, Seno S, Okuzaki D, Hirata H, Ogura H.
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Journal Title
Journal of Clinical Immunology
Volume: 43
Pages: 286~298
DOI
Peer Reviewed / Open Access
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[Journal Article] Smoking enhances the expression of angiotensin‐converting enzyme 2 involved in the efficiency of severe acute respiratory syndrome coronavirus 2 infection2023
Author(s)
Suzuki R, Ono Y, Noshita K, Kim KS, Ito H, Morioka Y, Tamura T, Okuzaki D, Tagawa T, Takenaka T, Yoshizumi T, Shimamura T, Iwami S, Fukuhara T.
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Journal Title
Microbiology and Immunology
Volume: 67
Pages: 22~31
DOI
Peer Reviewed
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