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准教授 下野　洋平
Associate Professor Yohei Shimono

履　　歴

出身／愛知県

1993年3月25日
名古屋大学医学部　卒業
1993年4月1日
名古屋第一赤十字病院　研修医
1995年4月1日
名古屋第一赤十字病院　医員（呼吸器内科）
1997年4月1日
名古屋大学大学院医学系研究科入学
2001年3月26日
名古屋大学大学院医学系研究科修了（医学博士）
2002年4月1日
日本学術振興会　特別研究員（PD）
2005年11月1日
米国スタンフォード大学医学部　幹細胞生物学・再生医学研究所　博士研究員（Michael Clarke教授）
2009年7月1日
米国スタンフォード大学医学部　幹細胞生物学・再生医学研究所　リサーチ・アソシエイト
2010年8月1日
神戸大学大学院医学研究科生化学・分子生物学講座　分子細胞生物学分野　講師
2011年4月1日
神戸大学大学院医学研究科生化学・分子生物学講座　分子細胞生物学分野　准教授
○資格／
日本内科学会総合内科専門医、日本医師会認定産業医
○所属学会等／
日本内科学会、日本癌学会、日本臨床腫瘍学会、日本呼吸器学会、日本分子生物学会、日本サイトメトリー学会

原　　著

  1. Mukohyama J, Iwakiri D, Zen Y, Mukohara T, Minami H, Kakeji Y, Shimono Y*. Evaluation of the risk of lymphomagenesis in xenografts by the PCR-based detection of EBV BamHI W region in patient cancer specimens. Oncotarget, 2016, in press
  2. Mukohyama J, Shimono Y*, Yamashita K, Sumi Y, Mukohara T, Minami H, Kakeji Y. Effect of Xenotransplantation Site on MicroRNA Expression of Human Colon Cancer Stem Cells. Anticancer Research, 36: 3679-86, 2016.
  3. Ijuin T, Takeuchi Y, Shimono Y, Fukumoto M, Tokuda E, Takenawa T. Regulation of CD44 expression and focal adhesion by Golgi phosphatidylinositol 4-phosphate in breast cancer. Cancer Science, 107: 981-90, 2016.
  4. Kitayama M, Mizutani K, Maruoka M, Mandai K, Sakakibara S, Ueda Y, Komori T, Shimono Y, Takai Y. A Novel Nectin-mediated Cell Adhesion Apparatus That Is Implicated in Prolactin Receptor Signaling for Mammary Gland Development. Journal of Biological Chemistry, 291:5817-5831, 2016.
  5. Sakaguchi M, Hisamori S, Oshima N, Sato F, Shimono Y, Sakai Y. miR-137 Regulates the Tumorigenicity of Colon Cancer Stem Cells through the Inhibition of DCLK1. Molecular Cancer Research, 14: 354-62, 2016.
  6. Nobutani K, Shimono Y, Mizutani K, Ueda Y, Suzuki T, Kitayama M, Minami A, Momose K, Miyawaki K, Akashi K, Azuma T, Takai Y. Downregulation of CXCR4 in metastasized breast cancer cells and implication in their dormancy. PLoSOne, 10: e0130032, 2015.
  7. Imamura Y, Mukohara T, Shimono Y, Funakoshi Y, Chayahara N, Toyoda M, Kiyota N, Takao S, Kono S, Nakatsura T, Minami H. Comparison of 2D- and 3D-culture models as drug-testing platforms in breast cancer. Oncology Reports, 33: 1837-1843, 2015.
  8. Isobe T, Hisamori S, Hogan DJ, Zabala M, Hendrickson DG, Dalerba P, Cai S, Scheeren F, Kuo AH, Sikandar SS, Lam JS, Qian D, Dirbas FM, Somlo G, Lao K, Brown PO, Clarke MF, Shimono Y*. miR-142 regulates the tumorigenicity of human breast cancer stem cells through the canonical WNT signaling pathway. eLife, 3: e01977, 2014.
  9. Suzuki T, Mizutani K, Minami A, Nobutani K, Kurita S, Nagino M, Shimono Y*, Takai Y*. (*Corresponding author). Suppression of the TGF-β1-induced protein expression of SNAI1 and N-cadherin by miR-199a. Genes to Cells, 2014, 19: 667-675, 2014.
  10. Nobutani K, Shimono Y, Yoshida M, Mizutani K, Minami A, Kono S, Mukohara T, Yamasaki T, Itoh T, Takao S, Minami H, Azuma T, Takai Y. Absence of primary cilia in the cell cycle-arrested human breast cancer cells. Genes to Cells, 19: 141-152, 2014.
  11. Ekyalongo RC, Mukohara T, Funakoshi Y, Tomioka H, Kataoka Y, Shimono Y, Chayahara N, Toyoda M, Kiyota N, Minami H. TYRO3 as a potential therapeutic target in breast cancer. Anticancer Research, 34: 3337-3345, 2014.
  12. Funakoshi Y, Mukohara T, Ekyalongo RC, Tomioka H, Kataoka Y, Shimono Y, Chayahara N, Toyoda M, Kiyota N, Fujiwara Y, Minami H. Regulation of MET kinase inhibitor resistance by copy number of MET in gastric carcinoma cells. Oncology Research, 21: 287-293, 2013.
  13. Sugiyama H, Mizutani K, Kurita S, Okimoto N, Shimono Y, Takai Y. Interaction of Necl-4/CADM4 with ErbB3 and integrin 6 4 and inhibition of ErbB2/ErbB3 signaling and hemidesmosome disassembly. Genes to Cells, 18: 519-528, 2013.
  14. Momose K, Minami A, Shimono Y, Mizutani K, Nobutani K, Azuma T, Takai Y. miR-214 and hypoxia down-regulate Necl-2/CADM1 and enhance ErbB2/ErbB3 signaling. Genes to Cells, 18: 195-202, 2013.
  15. Minami A, Shimono Y, Mizutani K, Nobutani K, Momose K, Azuma T, Takai Y. Reduction of the ST6 β-galactosamide α-2,6-sialyltransferase 1 (ST6GAL1)-catalyzed sialylation of nectin-like molecule 2/cell adhesion molecule 1 and enhancement of ErbB2/ErbB3 signaling by microRNA-199a. Journal of Biological Chemistry, 288: 11845-11853, 2013.
  16. Yoshida M, Shimono Y, Togashi H, Matsuzaki K, Miyoshi J, Akira Mizoguchi A, Komori T, Takai Y. Periderm cells covering palatal shelves have tight junctions and their desquamation reduces the polarity of palatal shelf epithelial cells in palatogenesis. Genes to Cells, 17: 455-472, 2012.
  17. Dalerba P, Kalisky T, Sahoo D, Rajendran PS, Rothenberg ME, Leyrat AA, Sim S, Okamoto J, Johnston DM, Qian D, Zabala M, Bueno J, Neff NF, Wang J, Shelton AA, Visser B, Hisamori S, Shimono Y, van de Wetering M, Clevers H, Clarke MF, Quake SR. Single-cell dissection of transcriptional heterogeneity in human colon tumors. Nature Biotechnology, 29: 1120-1127, 2011.
  18. Liu H, Patel MR, Prescher JA, Patsialou A, Qian D, Lin J, Wen S, Chang YF, Bachmann MH, Shimono Y, Dalerba P, Adorno M, Lobo N, Bueno J, Dirbas FM, Goswami S, Somlo G, Condeelis J, Contag CH, Gambhir SS, Clarke MF. Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models. Proceedings of the National Academy of Sciences U.S.A. 107: 18115-18120, 2010.
  19. Shimono Y, Zabala M, Cho RW, Lobo N, Dalerba P, Qian D, Diehn M, Liu H, Panula SP, Chiao E, Dirbas FM, Somlo G, Reijo Pera RA, Lao K, Clarke MF. Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell, 138: 592-603, 2009.
  20. Tsukamoto H, Kato T, Enomoto A, Nakamura N, Shimono Y, Jijiwa M, Asai N, Murakumo Y, Shibata K, Kikkawa F, Takahashi M. Expression of Ret finger protein correlates with outcomes in endometrial cancer. Cancer Science, 100: 1895-1901, 2009.
  21. Kato T, Shimono Y, Hasegawa M, Jijiwa M, Enomoto A, Asai N, Murakumo Y, Takahashi M. Characterization of the HDAC1 complex that regulates the sensitivity of cancer cells to oxidative stress. Cancer Research, 69: 3597-3604, 2009.
  22. Li B, Zhou J, Liu P, Hu J, Jin H, Shimono Y, Takahashi M, Xu G. Polycomb protein Cbx4 promotes SUMO modification of de novo DNA methyltransferase Dnmt3a. Biochemical Journal, 405: 369-378, 2007.
  23. Kee HJ, Kim JR, Nam KI, Park HY, Shin S, Kim JC, Shimono Y, Takahashi M, Jeong MH, Kim N, Kim KK, Kook H. Enhancer of polycomb1, a novel homeodomain only protein-binding partner, induces skeletal muscle differentiation. Journal of Biological Chemistry, 282: 7700-7709, 2007.
  24. Uchida M, Enomoto A, Fukuda T, Kurokawa K, Maeda K, Kodama Y, Asai N, Hasegawa T, Shimono Y, Jijiwa M, Ichihara M, Murakumo Y, Takahashi M. Dok-4 regulates GDNF-dependent neurite outgrowth through downstream activation of Rap1 and mitogen-activated protein kinase. Journal of Cell Science, 119: 3067-3077, 2006.
  25. Shimono K#, Shimono Y#, Shimokata K, Ishiguro N, Takahashi M (#equal contribution). Microspherule protein 1, Mi-2 , and RET finger protein associate in the nucleolus and up-regulate ribosomal gene transcription. Journal of Biological Chemistry, 280: 39436-39447, 2005.
  26. Morinaga T, Enomoto A, Shimono Y, Hirose F, Fukuda N, Dambara A, Jijiwa M, Kawai K, Hashimoto K, Ichihara M, Asai N, Murakumo Y, Matsuo S, Takahashi M. GDNF-inducible zinc finger protein 1 is a sequence-specific transcriptional repressor that binds to the HOXA10 gene regulatory region. Nucleic Acids Research, 33: 4191-4201, 2005.
  27. Matsuura T, Shimono Y, Kawai K, Murakami H, Urano T, Niwa Y, Goto H, Takahashi M. PIAS proteins are involved in the SUMO-1 modification, intracellular translocation and transcriptional repressive activity of RET finger protein. Experimental Cell Research, 308: 65-77, 2005.
  28. Kodama Y, Murakumo Y, Ichihara M, Kawai K, Shimono Y, Takahashi M. Induction of CRMP-2 by GDNF and analysis of the CRMP-2 promoter region. Biochemical and Biophysical Research Communications, 320: 108-115, 2004.
  29. Shimono Y, Murakami H, Kawai K, Wade PA, Shimokata K, Takahashi M. Mi-2 associates with BRG1 and RET finger protein at the distinct regions with transcriptional activating and repressing abilities. Journal of Biological Chemistry, 278: 51638-51465, 2003.
  30. Kawai K, Jijiwa M, Shimono Y, Kurokawa K, Murakumo Y, Ichihara M, Takahashi M. Establishment and characterization of mouse mammary carcinoma cell lines expressing RET with a multiple endocrine neoplasia 2A mutation. Cancer Science, 94: 992-997, 2003.
  31. Tezel G, Shimono Y, Murakumo Y, Kawai K, Fukuda T, Iwahashi N, Takahashi M. Role for O-glycosylation of RFP in the interaction with enhancer of polycomb. Biochemical and Biophysical Research Communications, 290: 409-414, 2002.
  32. Tezel G, Nagasaka T, Shimono Y, Takahashi M. Differential expression of RET finger protein in testicular germ cell tumors. Pathology International, 52: 623-627, 2002.
  33. Murakami H, Yamamura Y, Shimono Y, Kawai K, Kurokawa K, Takahashi M. Role of Dok1 in cell signaling mediated by RET tyrosine kinase. Journal of Biological Chemistry, 277: 32781-32790, 2002.
  34. Shimono Y, Murakami H, Hasegawa Y, Takahashi M. RET finger protein is a transcriptional repressor and interacts with enhancer of polycomb that has dual transcriptional functions. Journal of Biological Chemistry, 275: 39411-39419, 2000.
  35. Hayashi H, Ichihara M, Iwashita T, Murakami H, Shimono Y, Kawai K, Kurokawa K, Murakumo Y, Imai T, Funahashi H, Nakao A, Takahashi M. Characterization of intracellular signals via tyrosine 1062 in RET activated by glial cell line-derived neurotrophic factor. Oncogene, 19: 4469-4475, 2000.
  36. Murakami H, Iwashita T, Asai N, Shimono Y, Iwata Y, Kawai K, Takahashi M. Enhanced phosphatidylinositol 3-kinase activity and high phosphorylation state of its downstream signalling molecules mediated by ret with the MEN 2B mutation. Biochemical and Biophysical Research Communications, 262: 68-75, 1999.
  37. Ando M, Minami H, Ando Y, Sakai S, Shimono Y, Sugiura S, Saka H, Shimokata K, Hasegawa Y. Pharmacological analysis of etoposide in elderly patients with lung cancer. Clinical Cancer Research, 1999, 5: 1690-1695, 1999.
  38. Ohara H, Hasegawa Y, Kawabe T, Ichiyama S, Hara T, Shimono Y, Saito H, Shimokata K. Effect of gene transfer of tumor necrosis factor receptors into human lung carcinoma cell line. Japanese Journal of Cancer Research, 89: 589-595,1998.

総　　説

  1. Shimono Y, Mukohyama J, Isobe T, Johnston D, Dalerba P, Suzuki A. Organoid Assay of Human Cancer Stem Cells, In Organoids: Stem Cells, Structure and Function (Kursad Turksen, ed.), Springer, 2016, in press.
  2. Shimono Y, Mukohyama J, Nakamura S, Minami H. MicroRNA Regulation of Human Breast Cancer Stem Cells. Journal of Clinical Medicine, 5;2, 2016.
  3. 下野　洋平．乳がん幹細胞の潜在性臓器転移に関わる分子機構、BIO Clinica、30: 1007-1009、2015.
  4. 下野　洋平．細胞間接着　Eカドヘリンとネクチンのバリア機能への関与、臨床免疫・アレルギー科、64: 15-19、2015.
  5. 向山　順子、下野　洋平．臨床検体を活用した乳がん幹細胞研究、日本臨床、73: 831-835, 2015.
  6. 保仙直毅、下野洋平．実験医学別冊　直伝！フローサイトメトリー　面白いほど使いこなせる！（中内啓光　監、清田　純　編） がん幹細胞のソーティング、羊土社、180～193、2014.
  7. 下野　洋平．ヒト乳癌幹細胞　その提唱から11年のあゆみ、医学のあゆみ、250: 29-34、2014.
  8. 下野 洋平. 幹細胞疾患の分子機構―マイクロRNAとエピジェネティクス―、癌と化学療法、41: 290-293、2014.
  9. Mandai K, Rikitake Y, Shimono Y, Takai Y. Afadin/AF-6 and canoe: Roles in cell adhesion and beyond, In Progress in Molecular Biology and Translational Science (Frans van Roy, ed.), Elsevier, 116: 433-454, 2013.
  10. 鈴木 俊裕、下野 洋平．肺癌の新規診断・治療を目指した基礎研究　肺がん幹細胞、日本臨床 最新肺癌学、71: 263-267、2013.
  11. 下野 洋平．幹細胞異常と内科系疾患、現況と展望 幹細胞疾患とエピジェネティクス、日本内科学会雑誌、102: 2279-2283、2013.
  12. Shimono Y, Rikitake Y, Mandai K, Mori M, Takai Y. Immunoglobulin superfamily receptors and adherens junctions, In Adherens Junctions: From Molecular Mechanisms to Tissue Development and Disease (T. Harris, ed.), Springer, 137-170, 2012.
  13. 百瀬 健次, 下野 洋平．マイクロRNAによるがん幹細胞標的治療、遺伝子医学MOOK、133-138、2012.
  14. 下野　洋平、高井　義美．がん生物学イラストレイテッド（渋谷正史，湯浅保仁　編）
    がんの悪性化：浸潤と転移　上皮間葉転換、羊土社、223～232、2011.
  15. 南晶洋, 下野洋平. 治療標的としてのヒト乳がん幹細胞、BIO Clinica、26: 510-514、2011.
  16. 水谷清人, 下野洋平．上皮間葉転換と癌幹細胞、医薬ジャーナル、47: 2698-2701、2011.
  17. 下野洋平．がん幹細胞理論と肺がん、肺癌、51: 351、2011.
  18. 南　晶洋、下野　洋平．ヒト乳がん幹細胞－特性と幹細胞制御機構、実験医学増刊号、29: 3247-3253、2011.
  19. 下野　洋平、高井　義美．序論　がんの浸潤・転移研究
    信谷　健太郎、　下野　洋平．第15章　がん休眠、
    がんの浸潤・転移（高井義美　編）、南山堂、1～8、141～149、2011.
  20. 下野　洋平．microRNAによる癌幹細胞の"幹細胞性"制御、実験医学、28: 531-538、2010.
  21. Lobo NA, Shimono Y, Qian D, Clarke MF. The biology of cancer stem cells. Annual Review of Cell and Developmental Biology, 23: 675-699, 2007.
  22. 下野　洋平、加藤　琢哉、高橋　雅英．単一遺伝子病とゲノム　遺伝性悪性腫瘍　MEN1,MEN2　多発性内分泌腫瘍症2型(MEN2)、ゲノム医学、5: 601-606、2005.

受　　賞

  1. California Breast Cancer Research Program Postdoctoral Fellowship Award、2006－2009年

シンポジウム・海外発表

国際学会における発表（シンポジウム・口演・ポスター）

  1. Shimono Y, Cancer Stem Cells and Drug Resistance in Human Breast Cancer. Joint Symposium of Universit? de Li?ge and Kobe University, Kobe (Japan), 2015. 5.13.-14.
  2. Imamura Y, Mukohara T, Shimono Y, Funakoshi Y, Chayahara N, Toyoda M, Kiyota N, Takao S, Kono S, Nakatsura T, Minam H. Comparison of 2D- and 3D-culture models as drug-testing platforms in breast cancer. AACR Annual Meeting 2015, Philadelphia (U.S.A.), 2015.4.18.-22.
  3. Shimono Y, MicroRNA-mediated Regulation of the Human Cancer Stem Cells, Modern Aspect of Human Cancer Stem Cell /Cancer-initiating Cell. The 33rd Sapporo International Cancer Symposium, Sapporo (Japan), 2014.6.27.
  4. Shimono Y, Isobe T, Clarke MF, Regulation of the Wnt signaling pathway by microRNA-142 upregulated in human breast cancer stem cells. Keystone Symposium, Banff (Canada), 2014.2.2.-7.
  5. Shimono Y, MicroRNA Regulation of Human Breast Cancer Stem Cells. Session 1: Solid Tumor Stem Cells. The 26th Nagoya International Cancer Treatment Symposium, Nagoya (Japan), 2011.2.11.
  6. Shimono Y, microRNA regulation of human breast cancer stem cells and normal breast stem cells. 2nd ICSCN Symposium for Outstanding Young Researchers, San Francisco, California (U.S.A.), 2010.6.16.
  7. Shimono Y, Downregulation of miR-183 is a shared property of breast cancer stem cells and normal stem cells. 8th Joint Conference of the American Association for Cancer Research and the Japanese Cancer Association, Waikoloa, Hawaii (U.S.A.), 2010.2.8.
  8. Shimono Y, Clarke MF, MiRNA Profile Specific for Human Breast Cancer Stem Cells. Keystone Symposium, Keystone, Colorado (U.S.A.), 2008.3.29.
  9. Shimono Y, Clarke MF, Analysis of MicroRNA Expression in Breast Cancer Stem Cells. California Breast Cancer Research Program Symposium, Los Angeles, California (U.S.A.), 2007.11.19.

国内学会における発表（シンポジウム・ワークショップ）

  1. 下野　洋平、向山　順子、西村　建徳、磯部　大地、向原　徹、鈴木　聡、後藤　典子、南　博信. 臓器への潜在転移に関わるヒト乳がん幹細胞の解析、第26回日本サイトメトリー学会, 福岡, 2016.7.24.
  2. 下野　洋平. マイクロRNA研究の歴史と現状、ゲノム薬理学への応用について.第1回日本ゲノム薬理学会学術集会, 神戸, 2015.2.14.
  3. 下野　洋平. がん幹細胞特異的マイクロＲＮＡによるＷＮＴシグナル伝達系制御機構.日本癌学会シンポジウム / 共同利用・共同研究拠点シンポジウム, 金沢, 2015.1.21.
  4. 下野　洋平. がん幹細胞研究：現状と将来展望, 第11回日本臨床腫瘍学会学術集会教育講演, 仙台, 2013. 8.31.
  5. 下野　洋平.　幹細胞異常と内科系疾患、現況と展望: 幹細胞疾患とエピジェネティクス、日本内科学会講演会, 東京, 2013.4.13.
  6. 下野　洋平.　遺伝子発現解析からみたヒトがん幹細胞の幹細胞性、平成２３年度　文科省がん支援活動・厚労省対がん１０カ年研究合同公開シンポジウム, 東京, 2012.1.30.
  7. 下野　洋平. がん幹細胞理論と肺がん, 第52回日本肺癌学会総会, 大阪, 2011.11.3.
  8. 下野　洋平, MicroRNA Regulation of Human Breast Cancer Stem Cells and Normal Stem Cells.第9回日本臨床腫瘍学会学術集会, 横浜, 2011.7.21.
  9. 下野　洋平, 基礎研究と留学のすすめ. 第4回若手臨床血液学セミナー, 東京, 2011.11.19.
  10. 下野　洋平, 癌幹細胞理論と肺癌. 第26回日本肺癌学会ワークショップ, 名古屋, 2011.7.10.
  11. Yohei Shimono. Mammary hyperproliferation induced by APC-targeting microRNAs aberrantly expressed in human breast cancer stem cells., International Session: Cancer Stem Cells第69回日本癌学会学術総会, 大阪, 2010.9.23.
  12. 下野　洋平, Down-regulation of miRNA-200c Links Breast Cancer Stem Cells with Normal Stem Cells.第2回　NAGOYAグローバルリトリート, 愛知, 2010.2.26.
  13. 下野　洋平, MicroRNA regulation of human breast cancer stem cells: 特別講演関連シンポジウム Stem Cells and Cancer.　第67回日本癌学会学術総会, 名古屋, 2008.10.28.
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