简单介绍

李丁,2009年由中山大学‘百人计划’引入中山大学药学院担任教授, 博士生导师。1967年出生于山西省阳泉市。1989年北京大学化学系本科毕业,并于1995年在美国明尼苏达大学(University of Minnesota)化学系获博士学位。1995年到2000年在哈佛大学(Harvard University)化学系和德州农工大学(Texas A&M University)化学系担任研究助理和从事博士后研究工作。2000年到2009年在香港城市大学生物化学系先后担任助理教授和副教授。先后主持过十多项科研项目,其中包括2项国家自然科学基金项目、2项香港研究资助局科研项目、以及广东省和广州市科研项目。目前在SCI杂志上发表论文100多篇, 平均影响因子4.7。兼任教育部学位中心学位论文评议专家和广东省药学会药物化学专业委员会委员。曾获评优秀毕业论文指导教师。教授的课程包括化学生物学、药物化学,有机化学等。目前主要从事抗癌领域研究,包括小分子化合物通过调控基因启动子区域特殊DNA二级结构及其结合蛋白进而影响下游癌基因表达的分子机制、以小分子化合物为探针的端粒G-四链体及其结合蛋白Shelterin相互作用机制研究等。另外,还从事心血管疾病和老年痴呆症相关的一些分子机制研究。

研究方向

抗癌领域研究,包括小分子化合物通过调控基因启动子区域特殊DNA二级结构及其结合蛋白进而影响下游癌基因表达的分子机制、以小分子化合物为探针的端粒G-四链体及其结合蛋白Shelterin相互作用机制研究等。另外,还从事心血管疾病和老年痴呆症相关的一些分子机制研究。

教育经历

北京大学 化学系1985.9--1989.8本科毕业

美国明尼苏达大学 化学系1990.9--1995.4博士毕业

 

工作经历

1990--1995 研究和教学助理,美国明尼苏达大学,化学系
1995--1996 研究助理,美国哈佛大学,化学系
1996--2000 博士后美国德州农工大学,化学系
2000--2002 助理教授,香港城市大学,生物化学系
2002--2009 副教授,香港城市大学,生物化学系
2009—现在 教授,博士生导师,中山大学,药学院

教学情况

化学生物学、药物化学,有机化学

社会/学术任职

教育部学位中心学位论文评议专家

广东省药学会药物化学专业委员会委员

科研项目

  1. 香港研资局Competitive Earmarked Research Grant (CERG) 2001-2002, (Project No. 9040660, CityU 1110/01M), 200112-20045, 港币699,600项目负责人;

  2. 香港研资局Competitive Earmarked Research Grant (CERG) 2002-2003, (Project No. 9040756, CityU 1111/02M), 200212-200511, 港币816,000项目负责人;

  3. 中山大学,百人计划,80万人民币,20097-20116月;

  4. 国家自然科学基金,科学部主任基金,项目号36000-4103299G-四链体结构对hnRNP K 的转录和表达调控作用及其对下游基因c-myc 转录水平影响的分子机制研究,项目批准号21242010项目负责人,20131月至201312月,10万人民币。立项日期:20121225

  5. 国家自然科学基金面上项目,启动子G-四链体调控癌基因hnRNP K 及其通过i-motif影响下游c-myc 转录表达的分子机制研究,项目批准号21472252项目负责人,20151月至201812月,80万人民币。立项日期:2014117

  6. 广东省自然科学基金自由申请项目,hnRNP K 蛋白通过i-motif调控癌基因 c-myc 转录表达的分子机制研究,项目批准号2014A030313046项目负责人,20151月至20181月,10万人民币。立项日期:201576

  7. 广州市科技计划项目,转录调控因子hnRNP K通过i-motif调控癌基因 c-myc 转录表达的分子机制及其化学干预的意义,项目批准号201510010047项目负责人,20151月至201712月,20万人民币。立项日期:2015831

  8. 广东省自然科学基金自由申请项目,以小分子化合物为探针的端粒G-四链体及其结合蛋白Shelterin相互作用机制研究,项目批准号2017A030313089项目负责人,20175月至20205月,10万人民币。立项日期:20171225

 

论著专利

部分SCI论文(*通讯作者)

 

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. (杂志影响因子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 Subjects 2017, 1861 (12), 3246-3256(杂志影响因子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 Proteomics 2017, 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. (杂志影响因子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. 201551, 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. 201515 (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 Subjects 20141840, 3123-3130.

8.  “Mechanistic studies for tri-targeted inhibition of enzymes involved in cholesterol biosynthesis by green tea polyphenols” Ge, H.a; Liu, J.a; Zhao, W.; Wang, Y.; He, Q.; Wu, R.; Li, D.*; Xu, J.* Org. Biomol. Chem. 201412, 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 Subjects 20141840, 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 Subjects 20141840, 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 Subjects 20141840, 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 Subjects 201418401051-1062.

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 Subjects 201318304769-4777.

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 Subjects 20131830, 3635-3642. featured online on Global Medical Discovery [ISSN 1929-8536] (http://globalmedicaldiscovery.com)

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. 2012419 (3), 567-572. featured online on Global Medical Discovery [ISSN 1929-8536] (http://globalmedicaldiscovery.com)

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. 201247, 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. 201146, 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. 201046, 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. 200810 (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. 200810 (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. 200810 (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. 20079 (20), 3877-3880.

23.  “Bifunctional inhibitors of mevalonate kinase and mevalonate 5-diphosphate decarboxylase” Qiu, Y.; Li, D.Org. Lett. 20068 (6), 1013-1016.

24.“Intrinsic isomerase activity of medium-chain acyl-CoA dehydrogenase” Zeng, J.; Li, D.Biochemistry 200544 (17), 6715-6722.

25.“Crystal structure of precorrin-8x methyl mutase” Shipman, L.a,*; Li, D.a; Roessner, C.; Scott, A.; Sacchettini, J.* Structure 20019 (7), 587-596. (a. The first two authors contributed equally to this work)(杂志影响因子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. 1999121 (39), 9034-9042. (杂志影响因子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. Soc1998120 (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. Soc1996118 (1), 275-276.

 

总数:118