研究方向
抗癌領域研究,包括小分子化合物通過調控基因啟動子區域特殊DNA二級結構及其結合蛋白進而影響下游癌基因表達的分子機制、以小分子化合物為探針的端粒G-四鏈體及其結合蛋白Shelterin相互作用機制研究等。另外,還從事心血管疾病和老年痴呆症相關的一些分子機制研究。
人物經歷
教育經歷
北京大學 化學系1985.9--1989.8本科畢業
美國明尼蘇達大學 化學系1990.9--1995.4博士畢業
工作經歷
1990--1995 研究和教學助理,美國明尼蘇達大學,化學系
1995--1996 研究助理,美國哈佛大學,化學系
1996--2000 博士後,美國德州農工大學,化學系
2000--2002 助理教授,香港城市大學,生物化學系
2002--2009 副教授,香港城市大學,生物化學系
2009—現在 教授,博士生導師,中山大學,藥學院
教授課程
化學生物學、藥物化學,有機化學。
社會兼職
教育部學位中心學位論文評議專家
廣東省藥學會藥物化學專業委員會委員
學術成果
科研項目
香港研資局Competitive Earmarked Research Grant (CERG) 2001-2002, (Project No. 9040660, CityU 1110/01M), 2001年12月-2004年5月, 港幣699,600,項目負責人;
香港研資局Competitive Earmarked Research Grant (CERG) 2002-2003, (Project No. 9040756, CityU 1111/02M), 2002年12月-2005年11月, 港幣816,000,項目負責人;
中山大學,百人計畫,80萬人民幣,2009年7月-2011年6月;
國家自然科學基金,科學部主任基金,項目號36000-4103299,G-四鏈體結構對hnRNP K 的轉錄和表達調控作用及其對下游基因c-myc 轉錄水平影響的分子機制研究,項目批准號21242010,項目負責人,2013年1月至2013年12月,10萬人民幣。立項日期:2012年12月25日
國家自然科學基金面上項目,啟動子G-四鏈體調控癌基因hnRNP K 及其通過i-motif影響下游c-myc 轉錄表達的分子機制研究,項目批准號21472252,項目負責人,2015年1月至2018年12月,80萬人民幣。立項日期:2014年11月7日
廣東省自然科學基金自由申請項目,hnRNP K 蛋白通過i-motif調控癌基因 c-myc 轉錄表達的分子機制研究,項目批准號2014A030313046,項目負責人,2015年1月至2018年1月,10萬人民幣。立項日期:2015年7月6日
廣州市科技計畫項目,轉錄調控因子hnRNP K通過i-motif調控癌基因 c-myc 轉錄表達的分子機制及其化學干預的意義,項目批准號201510010047,項目負責人,2015年1月至2017年12月,20萬人民幣。立項日期:2015年8月31日
廣東省自然科學基金自由申請項目,以小分子化合物為探針的端粒G-四鏈體及其結合蛋白Shelterin相互作用機制研究,項目批准號2017A030313089,項目負責人,2017年5月至2020年5月,10萬人民幣。立項日期:2017年12月25日
代表性論文
1.“Syntheses and evaluation of new acridone derivatives for selective binding of oncogene c-myc promoter i-motifs in gene transcriptional regulation” Shu, B.; Cao, J.; Kuang, G.; Qiu, J.; Zhang, M.; Zhang, Y.; Wang, M.; Li, X.; Kang, S.; Ou, T.-M.; Tan, J.-H.; Huang, Z.-S.;Li, D.*Chem. Comm.2018,54, 2036-2039.(雜誌影響因子6.319)
2.“Interaction of Quindoline derivative with telomeric repeat-containing RNA induces telomeric DNA-damage response in cancer cells through inhibition of telomeric repeat factor 2”Zhang, Y.; Zeng, D.; Cao, J.; Wang, M.; Shu, B.; Kuang, G.; Ou, T.-M.; Tan, J.-H.; Gu, L.-Q.; Huang, Z.-S.;Li, D.*Biochim. Biophys. Acta - General Subjects2017,1861 (12), 3246-3256.(雜誌影響因子4.702)
3.“Curcusone C induces telomeric DNA-damage response in cancer cells through inhibition of telomeric repeat factor 2” Wang, M.; Cao, J.; Zhu, J.-Y.; Qiu, J.; Zhang, Y.; Shu, B.; Ou, T.-M.; Tan, J.-H.; Gu, L.-Q.; Huang, Z.-S.; Yin, S.;Li, D.*Biochim. Biophys. Acta -Proteins Proteomics2017,1865 (11), 1372-1382.
4. “Role of hairpin-quadruplex DNA secondary structural conversion in the promoter of hnRNP K in gene transcriptional regulation” Qiu, J.; Liu, J.; Chen, S.; Ou, T.-M.; Tan, J.-H.; Gu, L.-Q.; Huang, Z.-S.;Li, D.*Org. Lett.2015,17(18), 4584-4587.(雜誌影響因子6.579)
5.“Cp*Rh(III) and Cp*Ir(III)-catalysed redox-neutral C-H arylation with quinone diazides: quick and facile synthesis of arylated phenols” Zhang, S.-S.; Jiang, C.-Y.; Li, Q.; Huang, Z.-S.;Li, D.;* Wang, H*Chem. Comm.2015,51, 10240-10243.
6.“Biological function and medicinal research significance of G-quadruplex interactive proteins” Qiu, J.; Wang, M.; Zhang, Y.; Zeng, P.; Ou, T.-M.; Tan, J.-H.; Huang, S.-L.; An, L.-K.; Wang, H.; Gu, L.-Q.; Huang, Z.-S.;Li, D.*Curr. Top. Med. Chem.2015,15 (19), 1971-1987.
7.“Mechanistic studies on the anticancer activity of 2,4-disubstituted quinazoline derivative” Su, L.; Zheng, H.; Li, Z.; Qiu, J.; Chen, S.; Liu, J.; Ou, T.-M.; Tan, J.-H.; Gu, L.-Q.; Huang, Z.-S.;Li, D.*Biochim. Biophys. Acta - General Subjects2014,1840, 3123-3130.
8.“Mechanistic studies for tri-targeted inhibition of enzymes involved in cholesterol biosynthesis by green tea polyphenols” Ge, H.;Liu, J.; Zhao, W.; Wang, Y.; He, Q.; Wu, R.;Li, D.*; Xu, J.*Org. Biomol. Chem.2014,12, 4941-4951. (Highlighted by Chemistry World; a. The first two authors contributed equally to this work)
9.“Cellular nucleic acid binding protein suppresses tumor cell metastasis and induces tumor cell death by downregulating heterogeneous ribonucleoprotein K in fibrosarcoma cells” Qiu, J.; Chen, S.; Su, L.; Liu, J.; Xiao, N.; Ou, T.-M.; Tan, J.-H.; Gu, L.-Q.*; Huang, Z.-S.*;Li, D.*Biochim. Biophys. Acta - General Subjects2014,1840, 2244-2252.
10.“G-quadruplex-mediated regulation of telomere binding protein POT1 gene expression” He, Q.; Zeng, P.; Tan, J.-H.; Ou, T.-M.; Gu, L.-Q.; Huang, Z.-S.;Li, D.*Biochim. Biophys. Acta - General Subjects2014,1840, 2222-2233.
11.“Synthesis and characterization of 1H-phenanthro[9,10-d]imidazole derivatives as multifunctional agents for treatment of Alzheimer's disease” Liu, J.; Qiu, J.; Wang, M.; Wang, L.; Su, L.; Gao, J. Gu, Q.; Xu, J.; Huang, S.-L.; Gu, L.-Q.; Huang, Z.-S.*;Li, D.*Biochim. Biophys. Acta - General Subjects2014,1840, 2886-2903.
12.“Syntheses and characterization of non-bisphosphonate quinoline derivatives as new FPPS inhibitors” Liu, J.; Liu, W.; Ge, H.; Gao, J.; He, Q.; Su, L.; Xu, J.; Gu, L.-Q.; Huang, Z.-S.;Li, D.*Biochim. Biophys. Acta - General Subjects2014,1840,1051-1062.
13.“Mechanistic studies for the role of cellular nucleic-acid-binding protein (CNBP) in regulation of c-myc transcription” Chen, S.; Su, L.; Qiu, J.; Xiao, N.; Lin, J.; Tan, J.-H.; Ou, T.-M.; Gu, L.-Q.*; Huang, Z.-S.*;Li, D.*Biochim. Biophys. Acta - General Subjects2013,1830,4769-4777.
14.“Multi-target-directed design, syntheses, and characterization of fluorescent bisphosphonate derivatives as multifunctional enzyme inhibitors in mevalonate pathway” Gao, J.; Liu, J.; Qiu, Y.; Chu, X.; Qiao, Y;Li, D.*Biochim. Biophys. Acta - General Subjects2013,1830, 3635-3642. featured online on Global Medical Discovery [ISSN 1929-8536]
15.“Interaction of berberine derivative with protein POT1 affect telomere function in cancer cells” Xiao, N.; Chen, S.; Ma, Y.; Qiu, J.; Tan, J.-H.; Ou, T.-M.; Gu, L.-Q.; Huang, Z.-S.;Li, D.*Biochem. Biophys. Res. Comm.2012,419 (3), 567-572.(featured online on Global Medical Discovery [ISSN 1929-8536]
16.“Disubstituted quinazoline derivatives as a new type of highly selective ligands for telomeric G-quadruplex DNA” Li, Z.; Tan, J.-H.; He, J.-H.; Long, Y.; Ou, T.-M.;Li, D.*; Gu, L.-Q.; Huang, Z.-S.*Euro. J. Med. Chem.2012,47, 299-311.
17.“Design, synthesis, and characterization of piperazinedione-based dual protein inhibitors for both farnesyltransferase and geranylgeranyltransferase-I” Qiao, Y.; Gao, J.; Qiu, Y.; Wu, L.; Guo, F.; Lo, K.-W.;Li, D.*Euro. J. Med. Chem.2011,46, 2264-2273.
18.“Discovery of potent inhibitor for farnesyl pyrophosphate synthase in mevalonate pathway” Gao, J.; Chu, X.; Qiu, Y.; Wu, L.; Qiao, Y.; Wu, J.;Li, D.*Chem. Comm.2010,46, 5340-5342.
19.“Oct-2-en-4-ynoyl-CoA as a specific inhibitor of acyl-CoA oxidase” Zeng, J.; Wu, L.; Zhang, X.; Liu, Y.; Deng, G.;Li, D.*Org. Lett.2008,10 (19), 4287-4290.
20.“Comparative inhibition studies of enoyl-CoA hydratase 1 and enoyl-CoA hydratase 2 in long-chain fatty acid oxidation” Wu, L.; Lin, S.;Li, D.*Org. Lett.2008,10 (15), 3355-3358.
21.“Oct-2-yn-4-enoyl-CoA as a multifunctional enzyme inhibitor in fatty acid oxidation” Wu, L.; Liu, X.;Li, D.*Org. Lett.2008,10 (11), 2235-2238.
22.“Inactivation of thiolase by 2-alkynoyl-CoA via its intrinsic isomerase activity” Wu, L.; Zeng, J.; Deng, G.; Guo, F.; Li, N.; Liu, X.; Chu, X.;Li, D.*Org. Lett.2007,9(20), 3877-3880.
23.“Bifunctional inhibitors of mevalonate kinase and mevalonate 5-diphosphate decarboxylase” Qiu, Y.;Li, D.*Org. Lett.2006,8(6), 1013-1016.
24.“Intrinsic isomerase activity of medium-chain acyl-CoA dehydrogenase” Zeng, J.;Li, D.*Biochemistry2005,44 (17), 6715-6722.
25.“Crystal structure of precorrin-8x methyl mutase” Shipman, L.*;Li, D.; Roessner, C.; Scott, A.; Sacchettini, J.*Structure2001,9 (7), 587-596. (a. The first two authors contributed equally to this work)(雜誌影響因子4.945)
26.“The toxicity of methylenecyclopropylglycine: studies of the inhibitory effects of (methylenecyclopropyl)formyl-CoA on enzymes involved in fatty acid metabolism and the molecular basis of its inactivation of enoyl-CoA hydratases”Li, D.; Agnihotri, G.; Dakoji, S.; Oh, E.; Lantz, M.; Liu, H.-w.*J. Am. Chem. Soc.1999,121 (39), 9034-9042.(雜誌影響因子13.858)
27.“Spiropentylacetyl-CoA, a mechanism-based inactivator of acyl-CoA dehydrogenases”Li, D.; Zhou, H.-q.; Dakoji, S.; Shin, I.; Oh, E.; Liu, H.-w.*J. Am. Chem. Soc.1998,120 (9), 2008-2017.
28.“Mechanistic studies of the inactivation of crotonase by (methylenecyclopropyl)-formyl-CoA”Li, D.; Guo, Z.; Liu, H-w.*J. Am. Chem. Soc.1996,118 (1), 275-276.