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个人简介

王长山(Changshan Wang)内蒙古大学生命科学院教授,研究生导师 1973年10月出生,日本国立千叶大学医学博士,日本国立千叶大学医学研究院博士后。2015年7月回国加盟内蒙古大学生命科学院、现兼任日本国立千叶大学医学研究院外国人特别研究员。美国血液学会会员,国际干细胞学会会员,日本血液学会会员。曾经担任过,日本科学技术振兴机构Japan science and technology Agency (JST)研究助手和日本公益财团法人日美共同研究机关·放射线影响研究所Radiation Effects Research Foundation (RERF)协力研究员。 王长山博士长期致力于造血干细胞生物医学基础与转化研究,重心集中在基于动物模型和细胞模型,研究Polycomb group(PcG)蛋白复合体的正常与恶性造血干细胞自我更新、分化、迁移运动中的作用机制,以及与白血病发生发展过程中的调控功能。干细胞的命运决定,即其静息、恶性转化,自我更新或分化状态的选择受到细胞外信号及细胞内基因转录等多重机制的协同调控。其中PcG 蛋白可通过形成两个重要的表观遗传调控因子:PRC1(polycomb repressive complex 1)和PRC2(polycomb repressive complex 2)的蛋白复合物引起不同的染色质修饰来调控干细胞的生命活动。PcG蛋白复合体介导的基因表达调控已成为该领域研究的热点。我们实验室的主要临床转化研究方向包括利用小分子化合物体外扩增脐带血造血干细胞及其临床应用,用高通量筛选方法和药物化学方法筛选和研发肿瘤靶向治疗新类型DNA甲基化转移酶抑制剂。

研究领域

1. 造血干细胞命运决定分子调控机制及其临床转化研究 2. 血液肿瘤表观遗传调控与发病机制研究 3. 肿瘤干细胞干性维持表观遗传调控机制研究(乳腺癌,胃癌)

近期论文

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2016年: Nagisa Hasegawa, Motohiko Oshima, Goro Sashida, Hirotaka Matsui, Shuhei Koide, Atsunori Saraya, Changshan Wang*, Tomoya Muto, Kiyoko Takane, Atsushi Kaneda, Kazuya Shimoda, Chiaki Nakaseko, Koutaro Yokote, and Atsushi Iwama. Impact of combinatorial dysfunctions of Tet2 and Ezh2 on the epigenome in the pathogenesis of myelodysplastic syndrome. Leukemia2016 (IF12.104) Goro Sashida#, Changshan Wang#*, Takahisa Tomioka, Motohiko Oshima, Kazumasa Aoyama, Akinori Kanai, Makiko Mochizuki-Kashio, Hironori Harada, Kazuya Shimoda, and Atsushi Iwama. The loss of Ezh2 drives the pathogenesis of myelofibrosis and sensitizes tumor-initiating cells to bromodomain inhibition. Journal of Experimental Medicine 2016; 213(8): 1459-77. # equal contribution(IF12.515) Motohiko Oshima, Nagisa Hasegawa, Makiko Mochizuki-Kashio, Tomoya Muto, Satoru Miyagi, Shuhei Koide, Shogo Yabata, George Russel Wendt, Atsunori Saraya, Changshan Wang*, Kazuya Shimoda, Yutaka Suzuki, Atsushi Iwama. Ezh2 regulates the Lin28/let-7 pathway to restrict activation of fetal gene signature in adult hematopoietic stem cells. Experimental Hematology.2016 Apr;44(4):282-296.e3.(IF2.475) 2015年 Makiko Mochizuki-Kashio, Kazumasa Aoyama, Goro Sashida, Motohiko Oshima, Takahisa Tomioka, Tomoya Muto, Changshan Wang*, and Atsushi Iwama. Ezh2 loss in hematopoietic stem cells predisposes mice to develop heterogeneous malignanciesin an Ezh1-depenedent manner. Blood2015; 126(10): 1172-83.(IF 11.841) Changshan Wang*, Motohiko Oshima, Goro Sashida, Takahisa Tomioka, Nagisa Hasegawa, Makiko Mochizuki-Kashio, Yaeko Nakajima-Takagi, Yoichiro Kusunoki, Seishi Kyoizumi, Kazue Imai, Kei Nakachi, Atsushi Iwama. Non-Lethal Ionizing Radiation Promotes Aging-Like Phenotypic Changes of Human Hematopoietic Stem and Progenitor Cells in Humanized Mice. PLoS One. 2015 Jul 10;10 (7):e0132041.(IF 3.234) 2014年 YutaMishima#,Changshan Wang #*, Satoru Miyagi #, Atsunori Saraya#, Hiroyuki Hosokawa, Makiko Mochizuki-Kashio, Yaeko Nakajima-Takagi, Shuhei Koide, Masamitsu Negishi, Goro Sashida, Taku Naito, Tomoyuki Ishikura, Atsushi Onodera, Toshinori Nakayama, Daniel G. Tenen, Naoto Yamaguchi, Haruhiko Koseki, Ichiro Taniuchi & Atsushi Iwama. Histone acetylation mediated by Brd1 is crucial for Cd8 gene activation during early thymocyte development. Nature communications. 2014; 5: 5872.# equal contribution (IF 11.47) Changshan Wang*, Goro Sashida, Atsunori Saraya, Reiko Ishiga, Shuhei Koide, Motohiko Oshima, Kyoichi Isono, Haruhiko Koseki, and Atsushi Iwama. Depletion of Sf3b1 impairs proliferative capacity of hematopoietic stem cells but is not sufficient to induce myelodysplasia. Blood.2014;123(21): 3336-43.(IF 11.841) Goro Sashida, Hironori Harada, Hirotaka Matsui, Motohiko Oshima, MakikoYui, Yuka Harada, Satomi Tanaka, Makiko Mochizuki-Kashio, Changshan Wang*, Atsunori Saraya, Tomoya Muto,Yoshihiro Hayashi, Kotaro Suzuki, Hiroshi Nakajima, Toshiya Inaba, Haruhiko Koseki, Gang Huang, Toshio Kitamura & Atsushi Iwama. Ezh2 loss promotes RUNX1 mutant-induced myelodysplastic syndrome in cellintrinsic and extrinsic manners. Nature communications.5:4177. doi: 10.1038/ncomms5177. (IF 11.47) Satoru Miyagi, Shuhei Koide, GeorgeR. Wendt, Motohiko Oshima, Takaaki Konuma, Satoshi Yamazaki, Makiko Mochizuki-Kashio,Yaeko Nakajima-Takagi, Changshan Wang*, Tetsuhiro Chiba, IssayKita bayashi, Hiromitsu Nakauchi, and Atsushi Iwama. The Tif1b -Hp1 system maintains transcriptional integrity of hematopoietic stem cells, Stem Cell Reports.2014 Jan 23;2(2):145-52.(IF 7.023) Yuki Hayashi, Takao Kuroda, Hiroyuki Kishimoto, Changshan Wang*, Atsushi Iwama, Keiji Kimura. Downregulation of rRNA transcription triggers cell differentiation. PLoS ONE 9:e98586, 2014. (IF 3.234) 2007年~2013年 Changshan Wang*, Shunsuke Nakamura, Motohiko Oshima, Makiko Mochizuki-Kashio, Yaeko Nakajima-Takagi, Mitsujiro Osawa ,Yoichiro Kusunoki , Seishi Kyoizumi , Kazue Imai , Kei Nakachi and Atsushi Iwama. Compromised hematopoiesis and increased DNA damage following non-lethal ionizing radiation of a human hematopoietic system reconstituted in immunodeficient mice. International Journal of Radiation Biology 89, 132-137, 2013, Feb. (IF 1.687) Taito Nishino, Changshan Wang*, Makiko Mochizuki-Kashio, Mitsujiro Osawa, Hiromitsu Nakauchi, Atsushi Iwama. Ex vivo expansion of human hematopoietic stem cells by Garcinol, a potent inhibitor of histone acetyltransferase. PLoS ONE 6: e24298, 2011(IF 3.234) Yusuke Takeda, Chiaki Nakaseko, Hiroaki Tanaka, Masahiro Takeuchi, Makiko Yui, Atsunori Saraya, Satoru Miyagi, Changshan Wang*, Satomi Tanaka, Chikako Ohwada, Emiko Sakaida, Naoto Yamaguchi, KoutaroYokote, Lothar Hennighausen and Atsushi Iwama. Direct activation of STAT5 by ETV6-Lyn fusion protein promotes induction of myeloproliferative neoplasm with myelofibrosis. British Journal of Hematology. 153, 589-598, 2011. (IF 4.711) Shunsuke Suzuki, Ryuichi Ono, Takanori Narita, Andrew J. Pask, Geoffrey Shaw, Changshan Wang*, Takashi Kohda, Amber E. Alsop, Jennifer A. Marshall Graves,YujiKohara, Fumitoshi Ishino, Marilyn B. Renfree, Tomoko Kaneko-Ishino. Retrotransposon Silencing by DNA Methylation Can Drive Mammalian Genomic Imprinting. PLOS GENETICS. ( 2007 ) Apr 13;3 (4) (IF 7.528)

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