2003.09 - 2008.09
中国科学院上海药物研究所
,药物设计,博士,导师: 蒋华良 院士、沈旭 研究员
1999.09 - 2003.07
复旦大学
,生命科学院,生物科学,学士
2024.02 - 至今
上海交通大学
,化学化工学院,化学生物学系,教授
2014.10 - 2024.01
上海交通大学
,医学院-基础医学院,药理学与
化学生物学系,
研究员
2009.08 - 2014.08
美国芝加哥大学
,化学系,博士后,合作导师: Chuan He 教授
2008.10 - 2009.07
美国德州大学西南医学中心
,药理系,博士后,合作导师: Elliott Ross 教授
团队致力于核酸和蛋白等生物大分子化学修饰酶系的化学生物学研究,开展的方向包括:
-
DNA和RNA表观遗传修饰的化学生物学
发展核酸修饰的高通量检测技术,鉴定新的核酸修饰/去修饰酶系,阐明酶系催化调控机制和
在肿瘤等重大疾病中的致病机制,发展新型靶向药物。
-
蛋白修饰的化学生物学
发展蛋白共价化学修饰技术,阐明酶系的底物精准识别和催化分子机制,基于机制开展酶功能的定向进化,拓展酶催化剂的工业应用。
-
肿瘤代谢调控的化学生物学
发展质谱代谢流检测技术,鉴定新的抗肿瘤药物靶标,揭示
肿瘤发生发展机制,
发展小分子探针进行化学干预。
代表性论文专著
1.
L. Zhang
#
, Y.J. Mu
#
, T.T. Li
#
, J.Y. Hu, H.W. Lin,
L. Zhang*
.
Molecular basis of an atypical dsDNA 5mC/6mA bifunctional dioxygenase CcTet from
Coprinopsis cinerea
in catalyzing dsDNA 5mC demethylation.
Nucleic Acid Res.
2024. In press.
2.
L. Zhang
#
, H.C. Duan
#
, M. Paduch
#
, J.Y. Hu, C. Zhang, Y.J. Mu, H.W. Lin, C. He, A.A. Kossiakoff, G.F. Jia*,
L Zhang
*.
The Molecular Basis of Human ALKBH3 Mediated RNA
N
1
-methyladenosine (m
1
A) Demethylation.
Angew. Chem. Int. Ed.
, 2023, e202313900.
3.
J.S. Zhou
#
, L. Zhang
#
, Y.R. Wang
#
, W.Y. Song
#
, Y.Z. Huang, Y.J. Mu, W. Schmitz, S.Y. Zhang, H.W. Lin, H.Z. Chen, F. Ye,
L Zhang
*. The Molecular Basis of Catalysis by SDR Family Members KetoacylACP Reductase FabG and Enoyl-ACP Reductase FabI in Type-II Fatty Acid Biosynthesis.
Angew. Chem. Int. Ed.
, 2023, 62, 46, e202313109.
4.
L. Zhang
#
, W.Y. Song
#
, T.T. Li, Y.J., Mu, P. Zhang, J.Y. Hu, H.W. Lin, J. Zhang, H. Gao*,
L. Zhang
*. Redox switching mechanism of the Adenosine 5'-phosphosulfate kinase domain (APSK2) of human PAPS synthase 2.
Structure
. 2023, 31, 826-835.
5.
X. Peng, S.l. Zhang, Y.Y. Wang, Z.C Zhou, Z.X. Yu, Z.X. Zhong,
L. Zhang
, Z.S. Chen, F. Claret, M. Elkabets, F. Wang, R. Wang, H.W. Lin, D.X. Kong, H. Liang. Stellettin B sensitizes glioblastoma to DNA-damaging treatments by suppressing PI3K-mediated homologous recombination repair.
Adv. Sci.
, 2022, 10, e2205529.
6.
Y.J. Mu
#
, L. Zhang
#,
*, J.Y. Hu
#
, J.S. Zhou, H.W. Lin, C. He, H.Z. Chen*,
L. Zhang*
. A fungal dioxygenase CcTet serves as a eukaryotic 6mA demethylase on duplex DNA.
Nat. Chem. Biol.
, 2022, 18, 733-741. (Highlighted by
Nat. Chem. Biol.
"Making a 6mA demethylase").
7.
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.
8.
P. Zhang
#
, L. Zhang
#,
*
, Z.Y. Hou, H.W. Lin, H. Gao
*
,
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.
9.
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.
10.
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.
11.
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.
12.
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.
13.
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*,
L. Zhang
*. Thymine DNA glycosylase recognizes the geometry alteration of minor grooves induced by 5-formylcytosine and 5-carboxylcytosine.
Chem. Sci.
2019, 10, 7407.
14.
S.Q. Shen
#
, X.D. Hang
#
, J.J. Zhuang
#
, L. Zhang*, H.K. Bi*,
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.
15.
X. Zhang
#
, L.H. Wei
#
, Y.X. Wang
#
, Y. Xiao
#
, J. Liu, W. Zhang, N. Yan, G.B. Amu, X.J. Tang,
L. Zhang
*, 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.
16.
L. Zhang, J.F. Xiao, J.R. Xu, T.R. Fu, Z.W. Cao, L. Zhu, H.Z. Chen, X. Shen, H.L. Jiang,
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.
招收硕士/博士研究生、博士后及科研助理!