簡(jiǎn)歷
繆澤鴻,博士,中國(guó)科學(xué)院上海藥物研究所研究員、博士生導(dǎo)師、研究組長(zhǎng)。從事抗腫瘤新藥研究研發(fā)及分子細(xì)胞作用機(jī)制研究,著重圍繞腫瘤DNA修復(fù)和耐藥展開(kāi)創(chuàng)新型抗腫瘤藥物發(fā)現(xiàn)及相關(guān)機(jī)制研究。已在SCI學(xué)術(shù)期刊發(fā)表論文80余篇,包括Cancer Res (6篇)、Int J Cancer (3篇)、Cell Death Dis (2篇)、Nat Prod Rep、Trends Pharmacol Sci等藥理學(xué)和腫瘤學(xué)領(lǐng)域的重要期刊;參加編寫(xiě)國(guó)際專(zhuān)著2本、國(guó)內(nèi)專(zhuān)著3本;主持完成具有自主知識(shí)產(chǎn)權(quán)的抗腫瘤1.1類(lèi)新藥鹽酸希明替康獲國(guó)家食品藥品監(jiān)督管理局臨床試驗(yàn)批件2份,正在進(jìn)行I期臨床試驗(yàn);正在主持具有自主知識(shí)產(chǎn)權(quán)的抗腫瘤1.1類(lèi)新藥鹽酸美呋哌瑞和SOMCL-9112的臨床前研究,預(yù)計(jì)年內(nèi)將進(jìn)行臨床試驗(yàn)申報(bào);獲授權(quán)發(fā)明專(zhuān)利13項(xiàng)、申請(qǐng)國(guó)內(nèi)外發(fā)明專(zhuān)利 19 項(xiàng)。先后主持或參與國(guó)家重大新藥創(chuàng)制新藥臨床前研究項(xiàng)目、關(guān)鍵技術(shù)研究項(xiàng)目、國(guó)家重大科學(xué)研究計(jì)劃項(xiàng)目、國(guó)家自然科學(xué)基金面上項(xiàng)目、重點(diǎn)項(xiàng)目、創(chuàng)新群體項(xiàng)目等;入選國(guó)家杰出青年科學(xué)基金(2010)、中國(guó)科學(xué)院“百人計(jì)劃”(2010)、中國(guó)科學(xué)院科技創(chuàng)新交叉與合作團(tuán)隊(duì)(2012)、上海市優(yōu)秀學(xué)術(shù)帶頭人計(jì)劃(2013)及上海市浦江人才計(jì)劃(2008)等人才計(jì)劃;曾獲得國(guó)家自然科學(xué)獎(jiǎng)二等獎(jiǎng)(2009,排名第二)、上海市自然科學(xué)獎(jiǎng)一等獎(jiǎng)(2007,排名第二)、全國(guó)百篇優(yōu)秀博士論文獎(jiǎng)(2005)、中國(guó)科學(xué)院院長(zhǎng)特別獎(jiǎng)(2004)、中國(guó)科學(xué)院優(yōu)秀博士學(xué)位論文(2004)、上海藥學(xué)科技一等獎(jiǎng)(2004,排名第二)及中國(guó)藥理學(xué)會(huì)Servier獎(jiǎng)(2003)。
教育經(jīng)歷
09/2000-07/2003,中國(guó)科學(xué)院上海藥物研究所,理學(xué)博士
09/1993-07/1996,中國(guó)醫(yī)學(xué)科學(xué)院協(xié)和醫(yī)科大學(xué)腫瘤研究所,醫(yī)學(xué)碩士
09/1982-07/1988,華西醫(yī)科大學(xué)醫(yī)學(xué)專(zhuān)業(yè)(六年制),醫(yī)學(xué)學(xué)士
工作經(jīng)歷
08/2009-至今,中國(guó)科學(xué)院上海藥物研究所,腫瘤藥理學(xué)研究員、博士生導(dǎo)師、課題組長(zhǎng)
10/2006-08/2009,中國(guó)科學(xué)院上海藥物研究所,腫瘤藥理學(xué)副研究員、研究員、博士生導(dǎo)師
10/2004-09/2006,美國(guó)國(guó)立衛(wèi)生研究院國(guó)家癌癥研究所(NCI, NIH),分子腫瘤藥理學(xué)Visiting Fellow
07/2003-09/2004,中國(guó)科學(xué)院上海藥物研究所,腫瘤藥理學(xué)副研究員
07/1988-08/2000,四川瀘州醫(yī)學(xué)院藥理教研室,藥理學(xué)助教、講師、副教授、教研室副主任
研究方向
腫瘤藥理學(xué)。從事抗腫瘤新藥研究研發(fā)及抗腫瘤作用機(jī)制研究,著重圍繞腫瘤DNA損傷修復(fù)和腫瘤耐藥展開(kāi)創(chuàng)新型抗腫瘤藥物發(fā)現(xiàn)與研發(fā)以及相關(guān)機(jī)制研究
科研成果
1.抗腫瘤I類(lèi)新藥研究
(1)鹽酸希明替康
(2)鹽酸美呋哌瑞
(3)SOMCL-9112
(4)選擇性PARP1抑制劑與選擇性PARP2抑制劑發(fā)現(xiàn)研究
(5)微管-Top2雙重抑制劑
(6)RIP3抑制劑
(7)具有我國(guó)特色的中藥有效成分的靶點(diǎn)發(fā)現(xiàn)和新藥研究
2.抗腫瘤作用和機(jī)制研究
(1)PARP抑制劑的作用和機(jī)制
(2)抗耐藥抗腫瘤化合物作用與機(jī)制
(3)其它:RIP3及其抑制劑
承擔(dān)科研項(xiàng)目情況
1.新藥研究國(guó)家重點(diǎn)實(shí)驗(yàn)室自主研究課題,針對(duì)PARP和S1P在腫瘤DNA修復(fù)及代謝中的調(diào)控機(jī)制和化學(xué)干預(yù)研究,子課題負(fù)責(zé)人,2014.3-2016.4
2.國(guó)家自然基金面上項(xiàng)目,RIP3:抗腫瘤分子靶點(diǎn)發(fā)現(xiàn)及其化學(xué)干預(yù)研究,項(xiàng)目負(fù)責(zé)人,2014.1-2017.12
3.上海市科委優(yōu)秀學(xué)術(shù)帶頭人計(jì)劃,中藥丹參生物活性成分丹參酮I的抗腫瘤多藥耐藥作用及分子機(jī)制研究,項(xiàng)目負(fù)責(zé)人,2013.7-2015.6
4.上海市科委 “科技創(chuàng)新行動(dòng)計(jì)劃”項(xiàng)目,抗腫瘤PARP1抑制劑SOMCL-9112和SOMCL-9121成藥性研究,項(xiàng)目負(fù)責(zé)人,2012.9-2015.9
5.新藥研究國(guó)家重點(diǎn)實(shí)驗(yàn)室自主研究課題,抗腫瘤新靶點(diǎn)的研究,子課題負(fù)責(zé)人,2012.4-2014.4
6.中國(guó)科學(xué)院科技創(chuàng)新交叉與合作團(tuán)隊(duì)項(xiàng)目,創(chuàng)新型抗腫瘤藥物發(fā)現(xiàn)及相關(guān)基礎(chǔ)研究,項(xiàng)目負(fù)責(zé)人,2012.1-2014.12
7.國(guó)家重大新藥創(chuàng)制重大專(zhuān)項(xiàng)關(guān)鍵技術(shù)研究,抗腫瘤藥物早期成藥性評(píng)價(jià)關(guān)鍵技術(shù)研究,項(xiàng)目負(fù)責(zé)人,2012.1-2015.12
8.國(guó)家重大新藥創(chuàng)制重大專(zhuān)項(xiàng)創(chuàng)新藥物研究開(kāi)發(fā),新型PARP-1抑制劑的設(shè)計(jì)優(yōu)化和成藥性研究,參與,2012.1-2015.12
9.國(guó)家重大科學(xué)研究計(jì)劃項(xiàng)目,新型納米藥物降低肝癌細(xì)胞耐藥性的機(jī)制和藥效學(xué)研究,課題負(fù)責(zé)人,2012.1-2016.8
10.國(guó)家杰出青年科學(xué)基金,抗腫瘤藥物藥理,項(xiàng)目負(fù)責(zé)人,2011.1-2014.12
11.國(guó)家自然基金創(chuàng)新群體科學(xué)基金,針對(duì)分子靶點(diǎn)的抗腫瘤藥物發(fā)現(xiàn)及其機(jī)理研究,參與,2011.1-2016.12
12.國(guó)家自然基金面上項(xiàng)目,新型有絲分裂抑制劑MT7分子靶標(biāo)的發(fā)現(xiàn)、確證及分子機(jī)制研究,項(xiàng)目負(fù)責(zé)人,2009.1-2011.12
代表論著
1. Jia-Xin Li, Jian-Ming Feng, Yan Wang, Xiao-Hua Li, Xu-Xing Chen, Yi Su,Yan-Yan Shen, Yi Chen, Bing Xiong, Chun-Hao Yang, Jian Ding, Ze-Hong Miao*. The B-RafV600E Inhibitor Dabrafenib Selectively Inhibits RIP3 and Alleviates Acetaminophen-Induced Liver Injury. Cell Death Dis. 2014; 5: e1278.
2. Wei Wang, Ying-Qing Wang, Tao Meng, Jun-Mei Yi, Xia-Juan Huan, Lan-Ping Ma, Lin-Jiang Tong, Yi Chen, Jian Ding, Jing-Kang Shen*, Ze-Hong Miao*. MCL-1 Degradation Mediated by JNK Activation via MEKK1/TAK1-MKK4 Contributes to Anticancer Activity of New Tubulin Inhibitor MT189. Mol Cancer Ther. 2014;13; 1480-1491.
3. Lei Xu, Jian-Ming Feng, Jia-Xin Li, Jin-Mei Zhu, Lin-Jiang Tong, Shan-Shan Song, Yi Chen, Fu-Lin Lian, Ya-Ping Li*, Dong-Hai Lin, Jian Ding, Ze-Hong Miao*. Tanshinone-1 induces tumor cell killing, enhanced by inhibition of secondary activation of signaling networks. Cell Death Dis. 2013;4:e905.
4. Na Ye, Chuan-Huizi Chen, Tian-Tian Chen, Zilan Song, Jin-Xue He, Xia-Juan Huan, Shan-Shan Song, Qiufeng Liu, Yi Chen, Jian Ding, Yechun Xu*, Ze-Hong Miao*, Ao Zhang*. Design, synthesis and biological evaluation of a series of benzo[de][1,7]naphthyridin-7(8h)-ones bearing a longer chain as novel PARP1 inhibitors. J Med Chem. 2013; 56:2885u20132903.
5. Zhao-Li Zhou, Ya-Xi Yang, Jian Ding, Yuan-Chao Li*, Ze-Hong Miao*. Triptolide: structural modifications, structure-activity relationships, bioactivities, clinical development and mechanisms. Nat Prod Rep. 2012; 29: 457-475.
6. Stefano Giustino Manzo, Zhao-Li Zhou, Ying-Qing Wang, Jessica Marinello, Jin-Xue He, Yuan-Chao Li, Jian Ding, Giovanni Capranico*, Ze-Hong Miao*. Natural product triptolide mediates cancer cell death by triggering CDK7-dependent degradation of RNA polymerase II. Cancer Res. 2012; 72: 5363-5373.
7. Bing Yu, Mei-Hong Li, Wei Wang, Ying-Qing Wang, Yi Jiang, Sheng-Ping Yang, Jian-Min Yue, Jian Ding*, Ze-Hong Miao*. Pseudolaric acid B-driven phosphorylation of c-Jun impairs its role in stabilizing HIF-1alpha: a novel function-converter model. J Mol Med (Berl). 2012; 90:971u2013981.
8. Zhixiang Zhang, Tao Meng, Na Yang, Wei Wang, Bing Xiong, Yi Chen, Lanping Ma, Jingkang Shen, Ze-Hong Miao*, Jian Ding*. MT119, a new planar-structured compound, targets the colchicine site of tubulin arresting mitosis and inhibiting tumor cell proliferation. Int J Cancer .2011; 129:214-224.
9. Zhao-Li Zhou, Zhi-Guo Luo, Bing Yu, Yi Jiang, Yi Chen, Jian-Ming Feng, Mei Dai, Lin-Jiang Tong, Zheng Li, Yuan-Chao Li, Jian Ding, Ze-Hong Miao*. Increased accumulation of hypoxia-inducible factor-1α with reduced transcriptional activity mediates the antitumor effect of triptolide. Mol Cancer. 2010;9:268pp1-11.
10. Bing Yu, Ze-Hong Miao*, Yi Jiang, Mei-Hong Li, Na Yang, Ting Li, Jian Ding*. c-Jun protects HIF-1 from degradation via its Oxygen-Dependent-Degradation domain in a non-transcriptional manner. Cancer Res. 2009; 69:7704-7712.