1. 核酸表观遗传修饰通路关键酶的分子调控机制研究 新药发现

2. 核酸生物合成与代谢通路关键酶的分子机制研究 新药发现

3. 脂肪酸生物合成与代谢通路关键酶的分子机制研究和新药发现;

张良,博士,研究员,博士生导师,肿瘤化学生物学课题组组长,国家优秀青年科学基金获得者,上海市 高层次 人才 ,上海市曙光计划资助者,上海交通大学唐立新优秀学者奖获得者,上海交通大学基础医学院杰出员工。主要从事癌症相关的核酸与脂肪酸修饰调控分子机制研究和新药发现工作。通过综合运用化学生物学、结构生物学、细胞生物学、代谢组学和药学等技术手段,寻找肿瘤在核酸表观遗传修饰调控、核酸生物合成与代谢、及脂肪酸生物合成与代谢途径中的新靶标,阐明这些酶的分子作用新机制、筛选靶向的抗肿瘤新药物。近年来在国际重要学术刊物 ( Nature Chemical Biology , Natur e Communications , Cell Research , Chemical Science, JACS , PNAS ) 上发表 SCI 论文 4 0 余篇,他引 20 00 余次,获得多项国际 /国内技术专利并成功商业化。

1. 国家自然科学基金委面上项目, 20 21/ 01 20 24 /12 6 0 万,课题负责人

2 . 国家自然科学基金委重大研究计划(培育), 2019/01 2021/12 60 万元, 课题负责人

3. 国家自然科学基金委优秀青年科学基金项目, 2018 / 01 2020 / 12 130 万,课题负责人

4. 国家自然科学基金委面上项目, 2016 / 01 2019/12 65 万,课题负责人

5. 上海市 “曙光计划”项目, 2 021/01~2024/12 15 万,课题负责人

6. 上海市 “创新行动计划”生物医药科技支撑专项, 2 02 0 /0 9 ~202 3 / 09 20 万,课题负责人

7. 上海市高层次人才 2015-01 2017-12 100 万,课题负责人

论文与专著 >>>

1. J.S. Zhou, L. Zhang, L. Zhang* . Mechanism and Drug Discovery of Type-II Fatty Acid Biosynthesis Pathway. Acta Chimica Sinia , 2020, in press.

2. T. R. Fu # , L. P. Liu # , Q. L. Yang # , Y. X. Wang, P. Xu, L. Zhang, S. E. Liu, Q. Dai, Q. J. Ji, G. L. Xu, C. He, C. Luo* and L. Zhang *. Thymine DNA glycosylase recognizes the geometry alteration of minor grooves induced by 5-formylcytosine and 5-carboxylcytosine. Chem. Sci. 2019, 10, 7407.

3. X. Zhang # , L. H. Wei # , Y. X. Wang # , Y. Xiao # , J. Liu, W. Zhang, N. Yan, G. B. Amu, X. J. Tang, L. Zhang * and G. F. Jia*. Structural insights into FTO's catalytic mechanism for the demethylation of multiple RNA substrates. Proc. Natl. Acad. Sci. U.S.A . 2019, 116, 2919.

4. S. Q. Shen # , X. D Hang # , J. J. Zhuang # , L. Zhang*, H. K. Bi* and L. Zhang *. A back-door Phenylalanine coordinates the stepwise hexameric loading of acyl carrier protein by the fatty acid biosynthesis enzyme β-hydroxyacyl-acyl carrier protein dehydratase (FabZ). Int. J. Biol. Macromol . 2019, 128, 5.

5. L. Zhang, J. F. Xiao, J. R. Xu, T. R. Fu, Z. W. Cao, L. Zhu, H. Z. Chen, X. Shen, H. L. Jiang and L. Zhang* . Crystal structure of FabZ-ACP complex reveals a dynamic seesaw-like catalytic mechanism of dehydratase in fatty acid biosynthesis. Cell Res . 2016, 26, 1330.

6. L. Zhang # , W. Z. Chen # , L. M. Iyer, J. Hu, G. Wang, Y. Fu, M. Yu, Q. Dai, L. Aravind and C. He. A TET homologue protein from Coprinopsis cinerea (CcTET) that biochemically converts 5-Methylcytosine to 5-Hydroxymethylcytosine, 5-Formylcytosine, and 5-Carboxylcytosine. J. Am. Chem. Soc . 2014, 136, 4801.

7. L. Zhang # , K. E. Szulwach # , G. C. Hon # , C. X. Song, B. Park, M. Yu, X. Y. Lu, Q. Dai, X. Wang, C. R. Street, H. P. Tan, J. H. Min, B. Ren, P. Jin, C. He. Tet-mediated covalent labelling of 5-methylcytosine for its genome-wide detection and sequencing. Nat. Commun . 2013, 4, 1517.

8. L. Zhang , X. Y. Lu, J. Y. Lu, H. H. Liang, Q. Dai, G. L. Xu, C. Luo, H. L. Jiang, C. He. Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-modified DNA. Nat. Chem. Biol . 2012, 8, 328.

9. C. He, L. Zhang , C. X. Song, M. Yu. Composition and Methods Related to Modification of 5-methylcytosine (5mC). 2012, Publication number: WO WO2012138973 A3.

10. K. Jonas, C. He, T. A. Clark, L. Zhang , X. Y. Lu. Identification of 5-methyl-c in nucleic acid templates. 2013, Publication number: WO2013163207 A1.