1. DNA和RNA表观遗传去甲基化酶的分子机制研究和先导药物发现；

2. 细菌和哺乳动物细胞内脂肪酸合成途径关键酶的分子机制研究和先导药物发现；

3. 哺乳动物细胞内核苷酸合成途径关键酶的代谢机制研究和先导药物发现；

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，上海市曙光学者，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。团队主要致力于肿瘤相关分子调控机制研究和先导药物发现。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，阐明人体细胞中核酸表观遗传调控（DNA/RNA甲基化-去甲基化）、脂肪酸和核苷酸在细胞内合成过程中关键酶的分子机制，明确其在肿瘤发生发展过程中的作用和调控机制，并建立高通量实体药物筛选体系，筛选靶向性抗肿瘤先导药物。近年来以通讯作者在化学生物学国际旗舰学术刊物(Nature Chemical Biology、Nature Communications、Cell Research、Chemical Science、PNAS、Elife等)上发表一系列SCI论文，获得并转化多项国际/美国/国内技术发明专利。

1. 国家自然科学基金委面上项目，2021/01～2024/12，63万元，主持；

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，主持；

3. 国家自然科学基金委优秀青年科学基金项目，2018/01～2020/12，130万元，主持；

4. 国家自然科学基金委面上项目，2016/01～2019/12，65万元，主持；

5. 上海市2022年度“科技创新行动计划”生物医药科技支撑专项项目，2022/04～2025/03，20万元，主持；

6. 上海市2022年度“科技创新行动计划”生物医药科技支撑专项项目，2020/09～2023/09，20万元，主持；

7. 上海市“曙光计划”项目，2021/01~2024/12，15万元，主持；

8. 上海交通大学海外人才引进项目，2015/01～2019/12，200万，主持；

9. 985新药平台队伍配套，2015/03～2018/12，30万，主持；

1. Y.J. Mu^#, L. Zhang^#, *, J.Y. Hu^#, J.S. Zhou, H.W. Lin, C. He, H.Z. Chen*, and L. Zhang*. A fungal dioxygenase CcTet serves as a eukaryotic 6mA demethylase on duplex DNA. Nat. Chem. Biol., 2022, 18, 733.

2. R.Y. Shang, J. Cui, J.X. Li, X.X. Miao, L. Zhang, D.D. Xie, L. Zhang, H.W. Lin, W.H. Jiao. Nigerin and ochracenes J−L, new sesquiterpenoids from the marine sponge symbiotic fungus Aspergillus niger. Tetrahedron, 2022, 104, 132599.

3. P. Zhang^#, L. Zhang^#, *, Z.Y. Hou, H.W. Lin, H. Gao*, and L. Zhang*. Structural basis for the substrate recognition mechanism of ATP-sulfurylase domain of human PAPS synthase 2. Biochem. Biophys. Res. Commun., 2021, 586, 1.

4. J.S. Zhou^#, L. Zhang^#, L.P. Zeng^#, L. Yu^#, Y.Y. Duan^#, S.Q. Shen^#, J.Y. Hu, P. Zhang, W.Y. Song, X.X. Ruan, J. Jiang, Y.N. Zhang, L. Zhou, J. Jia, X.D. Hang, C.L Tian, H.Z. Chen*, J.E. Cronan*, H.K. Bi*, L. Zhang*. Helicobacter pylori FabX contains a [4Fe-4S] cluster essential for unsaturated fatty acid synthesis. Nat. Commun., 2021, 12, 6932.

5. G.K. Chen^#, J.S. Zhou^#, Y.L. Zuo, W.P. Huo, J. Peng, M. Li, Y.N. Zhang, T.T. Wang, L. Zhang, L. Zhang*, H.H. Liang*. Structural basis for diguanylate cyclase activation by its binding partner in Pseudomonas aeruginosa. Elife. 2021, 10, e67289.

6. S.H. Xiao^#, S.Q. Guo, J. Han, Y.L. Sun, M.C. Wang, Y.T. Chen, X.Y. Fang, F. Yang, Y.J. Mu, L. Zhang, Y.L. Ding, N.X. Zhang, H.L. Jiang, K.X. Chen, K.H. Zhao, C. Luo, S.J. Chen*. High-Throughput-Methyl-Reading (HTMR) assay: a solution based on nucleotide methyl-binding proteins enables large-scale screening for DNA/RNA methyltransferases and demethylases. Nucleic Acids Res., 2021, 50, e9.

7. J.S. Zhou, L. Zhang, L. Zhang*. Advances on Mechanism and Drug Discovery of Type-II Fatty Acid Biosynthesis Pathway. Acta Chimica Sinia, 2020, 78, 1383.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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 (PCT专利).

16. 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 (PCT专利).