中國(guó)工程院院士、教授、博士生導(dǎo)師

中國(guó)協(xié)和醫(yī)科大學(xué)研究生畢業(yè)(1987)，美國(guó)匹茲堡大學(xué)醫(yī)學(xué)院終身教職副教授(2002)、分子腫瘤學(xué)國(guó)家重點(diǎn)實(shí)驗(yàn)室主任(2002-)、中國(guó)醫(yī)學(xué)科學(xué)院副院長(zhǎng)(2005-)?，F(xiàn)任北京大學(xué)醫(yī)學(xué)部主任、北京大學(xué)腫瘤醫(yī)院/研究所教授(2016-)。教育部長(zhǎng)江學(xué)者，國(guó)家杰出青年基金獲得者，新世紀(jì)百千萬(wàn)人才工程國(guó)家級(jí)人選，國(guó)家自然科學(xué)基金委創(chuàng)新群體首席專家，國(guó)家973重大基礎(chǔ)研究項(xiàng)目首席科學(xué)家，享受?chē)?guó)務(wù)院政府特殊津貼。先后兼任中國(guó)微循環(huán)學(xué)會(huì)理事長(zhǎng)、中國(guó)抗癌協(xié)會(huì)副理事長(zhǎng)、國(guó)家生物醫(yī)藥技術(shù)戰(zhàn)略發(fā)展規(guī)劃專家組組長(zhǎng)國(guó)家新藥創(chuàng)制重大專項(xiàng)生物藥專家組組長(zhǎng)、《中國(guó)生化藥物》雜志主編、《科學(xué)通報(bào)》和《中華腫瘤雜志》副主編、《J Biol Chem》、《Carcinogenesis》、《Cancer Biol and Ther》、《Mol Oncol》等雜志編委。在《Nature》、《Cell》、《Science》、《J Clin Invest》等刊物上發(fā)表SCI論文200余篇，SCI他引12000多次。獲教育部自然科學(xué)一等獎(jiǎng)、華夏醫(yī)學(xué)科技一等獎(jiǎng)、中華醫(yī)學(xué)科技二等獎(jiǎng)和科技部“十一五”國(guó)家科技計(jì)劃執(zhí)行突出貢獻(xiàn)獎(jiǎng)。

電話：8819 6988(辦公室)

郵箱：qiminzhan@vip.163.com

主要研究領(lǐng)域

長(zhǎng)期致力于腫瘤分子生物學(xué)和腫瘤轉(zhuǎn)化醫(yī)學(xué)研究。系統(tǒng)揭示了多個(gè)細(xì)胞周期監(jiān)測(cè)點(diǎn)關(guān)鍵蛋白的作用和機(jī)制及其在細(xì)胞癌變和腫瘤診斷與個(gè)體化治療中的作用。近年系統(tǒng)研究了食管鱗癌的遺傳突變背景，發(fā)現(xiàn)了一批參與細(xì)胞周期調(diào)控、腫瘤發(fā)生及轉(zhuǎn)移相關(guān)的lncRNA，并對(duì)其功能和作用機(jī)制進(jìn)行了深入研究。

代表性研究成果

1、食管鱗癌基因組學(xué)變異研究

通過(guò)應(yīng)用高通量測(cè)序和比較基因組雜交芯片技術(shù)，利用基因組學(xué)、生物信息學(xué)、分子生物學(xué)、臨床病理學(xué)理論和技術(shù)完成了人類(lèi)食管鱗癌基因組變異的分析，發(fā)現(xiàn)158例食管鱗癌組織中存在8個(gè)明顯的基因變異，包括7個(gè)已知的腫瘤相關(guān)基因(TP53、RB1、CDKN2A、PIK3CA、NOTCH1、1NFE2L2、ADAM29)、1個(gè)以前從未報(bào)道過(guò)的腫瘤基因FAM135B。進(jìn)一步研究發(fā)現(xiàn)，F(xiàn)AM135B是一種能夠增加食管鱗癌細(xì)胞惡性程度的促癌基因。此外，研究還揭示了11q13.3-13.4擴(kuò)增區(qū)域(MIR548K),組蛋白調(diào)節(jié)基因突變(MLL2、ASHL1L、MLL3、SETD1B、CREBBP/EP300);發(fā)現(xiàn)PI3K等潛在藥靶;確定了Wnt、Cell cycle、Akt、Notch、RTK-Ras等食管癌發(fā)生發(fā)展相關(guān)重要通路等，該結(jié)果已于2014年發(fā)表于《Nature》上。

2、非編碼RNA的生物學(xué)功能和分子機(jī)制研究

GADD7是一個(gè)長(zhǎng)度為754nt的帶有Poly(A)尾的lncRNA，生長(zhǎng)阻滯和DNA損傷誘導(dǎo)其表達(dá)。我們研究發(fā)現(xiàn)GADD7特異性結(jié)合于TDP-43蛋白。同時(shí)TDP-43還可以與CDK6 mRNA的3’-UTR區(qū)域結(jié)合，從而增加CDK6 mRNA穩(wěn)定性。然而UV誘導(dǎo)下，GADD7表達(dá)增加，與TDP-43結(jié)合后有效抑制TDP-43與CDK6 mRNA的結(jié)合，從而導(dǎo)致CDK6 mRNA降解，最終參與調(diào)控細(xì)胞G1/S 檢驗(yàn)點(diǎn)。該結(jié)果已于2012年發(fā)表于《EMBO J》上。

3、腫瘤惡性進(jìn)展的分子生物學(xué)機(jī)制研究

通過(guò)對(duì)大量食管鱗癌(ESCC)及其它惡性腫瘤的臨床標(biāo)本進(jìn)行分析，以及在細(xì)胞和動(dòng)物水平的進(jìn)一步驗(yàn)證，確立了多種癌基因與ESCC及其它惡性腫瘤進(jìn)展的相關(guān)性，其中血小板活化因子受體PAFR誘導(dǎo)ESCC進(jìn)展的研究成果于2015年發(fā)表《Oncogene》上。機(jī)制研究顯示，PAFR能夠與黏著斑激酶FAK結(jié)合，誘導(dǎo)其激活PI3K/Akt/NF-κB信號(hào)通路，進(jìn)而調(diào)控下游多種促癌基因的表達(dá)，促進(jìn)食管鱗癌的惡性增殖，侵襲及誘導(dǎo)內(nèi)皮細(xì)胞血管新生的能力，闡明了PAFR誘導(dǎo)食管鱗癌進(jìn)展的機(jī)制。此外，通過(guò)使用具有成藥性的膽固醇包被的PAFR siRNA抑制小鼠荷瘤模型中食管鱗癌進(jìn)展及促癌基因的表達(dá)，進(jìn)一步為開(kāi)發(fā)以PAFR為靶點(diǎn)的信號(hào)通路抑制劑提供了理論依據(jù)。在非小細(xì)胞肺癌中的研究顯示，PAF/PAFR信號(hào)軸能夠通過(guò)激活小G蛋白，誘導(dǎo)JAK2/Src/STAT3信號(hào)通路的活性，而激活的STAT3能夠轉(zhuǎn)錄性激活PAFR表達(dá)并形成正反饋環(huán)，進(jìn)而介導(dǎo)PAFR調(diào)控的非小細(xì)胞肺癌上皮-間質(zhì)轉(zhuǎn)化及侵襲轉(zhuǎn)移。相關(guān)研究成果于2015年發(fā)表于《Cancer Research》上。

近五年代表性論文

1. Cheng C, Zhou Y, Li H, Xiong T, Li S, Bi Y, Kong P, Wang F, Cui H, Li Y, Fang X, Yan T, Li Y, Wang J, Yang B, Zhang L, Jia Z, Song B, Hu X, Yang J, Qiu H, Zhang G, Liu J, Xu E, Shi R, Zhang Y, Liu H, He C, Zhao Z, Qian Y, Rong R, Han Z, Zhang Y, Luo W, Wang J, Peng S, Yang X, Li X, Li L, Fang H, Liu X, Ma L, Chen Y, Guo S, Chen X, Xi Y, Li G, Liang J, Yang X, Guo J, Jia J, Li Q, Cheng X, Zhan Q*, Cui Y* (2016) Whole-Genome Sequencing Reveals Diverse Models of Structural Variations in Esophageal Squamous Cell Carcinoma. Am J Hum Genet 98(2): 256-74.

2. Dongdong Zhang, Weimin Zhang, Dan Li, Ming Fu, Runsheng Chen, and Qimin Zhan* (2015) GADD45A Inhibits autophagy by regulating the Interaction between BECN1 and PIK3C3. Autophagy 11(12): 2247-58.

3. Ling Zhang, Yong Zhou, Caixia Cheng, Heyang Cui, Le Cheng, Pengzhou Kong, Jiaqian Wang, Yin Li, Wenliang Chen, Bin Song, Fang Wang, Zhiwu Jia, Lin Li, Yaoping Li, Bin Yang, Jing Liu, Ruyi Shi, Yanghui Bi, Yanyan Zhang, Juan Wang, Zhenxiang Zhao, Xiaoling Hu, Jie Yang, Hongyi Li, Zhibo Gao, Gang Chen, Xuanlin Huang, Xukui Yang, Shengqing Wan, Chao Chen, Bin Li, Yongkai Tan, Longyun Chen, Minghui He, Sha Xie, Xiangchun Li, Xuehan Zhuang, Mengyao Wang, Zhi Xia, Longhai Luo, Jie Ma, Bing Dong, Jiuzhou Zhao, Yongmei Song, Yunwei Ou, Enming Li, Liyan Xu, Jinfen Wang, Yanfeng Xi, Guodong Li, Enwei Xu, Jianfang Liang, Xiaofeng Yang, Jiansheng Guo, Xing Chen, Yanbo Zhang, Qingshan Li, Lixin Liu, Yingrui Li, Xiuqing Zhang, Huanming Yang, Dongxin Lin, Xiaolong Cheng, Yongjun Guo, Jun Wang, Qimin Zhan*, and Yongping Cui* (2015) Genomic Analyses Reveal Mutational Signatures and Frequently Altered Genes in Esophageal SquamousCell Carcinoma. Am J Hum Genet 96(4): 597-611.

4. Jie Chen, Tian Lan, Weimin Zhang, Lijia Dong, Nan Kang, Shumin Zhang, Ming Fu, Bing Liu, Kangtai Liu, and Qimin Zhan* (2015) Feed-Forward Reciprocal Activation of PAFR and STAT3 Regulates Epithelial-Mesenchymal Transition in Non-Small Cell Lung Cancer. Cancer Res 75(19): 4198-210.

5. J Chen, T Lan, W Zhang, L Dong, N Kang, S Zhang, M Fu, B Liu, K Liu, C Zhang, J Hou and Q Zhan* (2015) Platelet-activating factor receptor-mediated PI3K/AKT activation contributes to the malignant development of esophageal squamous cell carcinoma. Oncogene 34(40): 5114-27.

6. Li D, Kang N, Ji J, Zhan Q* (2015) BRCA1 regulates transforming growth factor-β (TGF-β1) signaling through Gadd45a by enhancing the protein stability of Smad4. Mol Oncol 9(8):1655-66.

7. Jian Liu, Haijuan Wang, Fei Ma, Dongkui Xu, Yanan Chang, Jinlong Zhang, Jia Wang, Mei Zhao, Chen Lin, Changzhi Huang*, Haili Qian*, Qimin Zhan* (2015) MTA1 regulates higher-order chromatin structure and histone H1-chromatin. Mol Oncol 9(1): 218-35.

8. Dong Y, Zhao Q, Ma X, Ma G, Liu C, Chen Z, Yu L, Liu X, Zhang Y, Shao S, Xiao J, Li J, Zhang W, Fu M, Dong L, Yang X, Guo X, Xue L, Fang F, Zhan Q*, Zhang L* (2015) Establishment of a new OSCC cell line derived from OLK and identification of malignant transformation-related proteins by differential proteomics approach. Sci Rep 5: 12668.

9. Yongmei Song, Lin Li, Yunwei Ou, Zhibo Gao, Enmin Li, Xiangchun Li, Weimin Zhang, Jiaqian Wang, Liyan Xu, Yong Zhou, Xiaojuan Ma, Lingyan Liu, Zitong Zhao, Xuanlin Huang, Jing Fan, Lijia Dong, Gang Chen, Liying Ma,Jia Yang, Longyun Chen, Minghui He, Miao Li, Xuehan Zhuang, Kai Huang, Kunlong Qiu, Guangliang Yin, Guangwu Guo, Qiang Feng, Peishan Chen, Zhiyong Wu, Jianyi Wu, Ling Ma, Jinyang Zhao, Longhai Luo, Ming Fu, Bainan Xu, Bo Chen, Yingrui Li, Tong Tong, Mingrong Wang, Zhihua Liu, Dongxin Lin, Xiuqing Zhang, Huanming Yang, Jun Wang & Qimin Zhan* (2014) Identification of genomic alterations in oesophageal squamous cell cancer. Nature 509(7498): 91-5.

10. Jianzhong Cao, Yongmei Song, Nan Bi, Jie Shen, Wenyang Liu, Jing Fan, Guogui Sun, Tong Tong, Jie He, Yuankai Shi, Xun Zhang, Ning Lu, Yinghua He, Hongyu Zhang, KelongMa, Xiaoying Luo, Lei Lv, Hui Deng, Jing Cheng, Jingde Zhu, Luhua Wang, and Qimin Zhan* (2013) DNA Methylation-Mediated Repression of miR-886-3p Predicts Poor Outcome of Human Small Cell Lung Cancer. Cancer Res 73(11): 3326-35.

11. Xuefeng Liu, Dan Li, Weimin Zhang, Mingzhou Guo and Qimin Zhan* (2012) Long non-coding RNA gadd7 interacts with TDP-43 and regulates Cdk6 mRNA decay. EMBO J 31(23): 4415-27.

12. Yulin Chen, Dan Li, Dapeng Wang, Xuefeng Liu, Ning Yin, Yongmei Song, Shih Hsin Lu, Zhenyu Ju, and Qimin Zhan* (2012) Quiescence and Attenuated DNA Damage Response Promote Surivival of Esophageal Cancer Stem Cells. J Cell Biol 12:3643-3652.

近五年獲發(fā)明專利授權(quán)

1. 詹啟敏、李丹、宋詠梅、童彤、劉雪峰、付明. HULC siRNA及其在制備治療肝癌的藥物中的用途. ZL201010512412.5.

2. Qimin Zhan; Lühua Wang; Nan Bi; Yongmei Song; Jianzhong Cao; Wenyang Liu. USE OF TWO MICRORNA MOLECULARS IN LUNG CANCER PROGNOSIS AND MEDICINE PREPARATION. US 8,664,191,B2.

3. Qimin Zhan; Lühua Wang; Nan Bi; Yongmei Song; Jianzhong Cao; Wenyang Liu. USE OF TWO MICRORNA MOLECULARS IN LUNG CANCER PROGNOSIS AND MEDICINE PREPARATION. EP 2 462 951 B1.

4. 詹啟敏、王綠化、畢楠、宋詠梅、曹建忠、劉文揚(yáng). 兩個(gè)microRNA分子在肺癌預(yù)后及藥物制備中的用途. 日本 第5546064號(hào).

5. 詹啟敏、王綠化、畢楠、宋詠梅、曹建忠、劉文揚(yáng). 兩個(gè)microRNA分子在肺癌預(yù)后及藥物制備中的用途. ZL200980158671.8.

實(shí)驗(yàn)室成員