Dr. Wu is a professor and PhD mentor at the State Key Laboratory of Microbial Technology, Shandong University. He has been awarded the “Young Taishan Scholars” of Shandong Province, “Provincial Outstanding Youth Fund” and "High-level Young Talents" (“New Drug Creation” program) of Ministry of Education. He is a member of the Specialized Committee of Chinese Pharmacological Society and a member of the Young Editorial Board of Acta Pharmaceutica Sinica B. His group is mainly engaged in structural and molecular pharmacology research and drug discovery of transcription factor target proteins, as well as structural analysis and catalytic mechanism research of biosynthesis-related enzymes. Those studies have been published in Nature, Nature Chemical Biology, Nature Communications, PNAS, JACS and other journals.

·  Education Background

1999.9-2003.7, Shandong University, School of Life Sciences, Bachelor of Science in Biotechnology

2003.9-2008.7, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Ph.D in Drug Design

 ·  Working Experiences

2008.8-2011.7, University of California, Davis, USA, Postdoc

2011.8-2016.8, Sanford Burnham Institute for Medical Research, USA, Postdoc

2016.9-Present, State Key Laboratory of Microbial Technology, Shandong University, Professor

 ·  Research Field

Key Words: Molecular Ppharmacology, Structural Biology, Chemical Biology

Our research group focuses on the target proteins related to major diseases. Current research focuses on the "nuclear receptor-like" transcription factors, the bHLH-PAS (basic helix-loop-helix-PER-ARNT-SIM) family, which are closely related to many human diseases and generally contain small-molecule ligand-binding pockets. Therefore, it is the second family of transcription factors after nuclear receptors that can be used as potential drug targets. On one hand, a variety of experimental methods are used to study the structure and function of these proteins, and to reveal the interaction between proteins and ligands, as well as the molecular mechanism of ligand-regulated protein activity. On the other hand, through the design and construction of a variety of compound screening systems, new small-molecule ligands are found, and further through computational simulation and structural modification, new lead compounds with better activity are obtained.

In addition, in the field of synthetic biology, through the cooperation with a number of research groups, we study the key enzymes involved in various microbial synthetic pathways. By analyzing their protein structures, especially the complex structures of the enzymes and substrates, we reveal the catalytic mechanisms such as substrate selectivity, which provides key information for the rational modification of enzymes.

Relevant research results have been published in international academic journals such as Nature, Nature Chemical Biology, Nature Communications (4 papers), PNAS (2 papers), JACS, etc. The Google Scholar h-index value is 30.

·  Research Grants

10. Study on the structural mechanism of aryl hydrocarbon receptor (AHR) regulation by the new psoriasis drug Benvitimod and other ligands, National Natural Science Foundation of China, 2024/1-2027/12

9. Drug discovery and mechanism of agonists targeting hypoxia-inducible factor HIF-2α, Biomedical Joint Fund Project of Shandong Natural Science Foundation, 2023/1-2025/12

8. Identification of novel transcription factor targets and discovery of novel small-molecule ligands, Jinan Innovation Team Project, 2023/1-2025/12

7. Technology of directed culture and rational regulation of functional modules of microbiota, National Key Research and Development Program, 2022/12-2027/11

6. Discovery of hypoxia-inducible factor 3α (HIF-3α) targeting ligands and study of the mechanism of action, National Natural Science Foundation of China, 2022/1-2025/12

5. Research on drug discovery and mechanism of action based on structural biology, Shandong Provincial Natural Science Foundation for Distinguished Young Scholars, 2022/1-2024/12

4. Discovery of novel targeting molecules for "nucleoid receptor" transcription factors, State Key Laboratory of New Drug Research, 2021/5-2022/5

3. Shandong Taishan Scholars Young Experts Program, 2020/1-2024/12

2. Structural and functional studies of the aryl hydrocarbon receptor (AHR), a mediator of microbiota-host communications, NSFC Youth Fund Project, 2018/1-2020/12

1. Discipline Construction Funds for Qilu Young Scholars of Shandong University, 2016/9-2021/9

·  Representative Papers

I. Structure-function studies and drug discovery of transcription factor target proteins

12. Diao X, Shang Q, Guo M, Huang Y, Zhang M, Chen X, Liang Y, Sun X, Zhou F, Zhuang J, Liu SJ, Vogel CFA, Rastinejad F, Wu D. Structural basis for the ligand-dependent activation of heterodimeric AHR-ARNT complex. Nat Commun. 2025, 16: 1282.（sole corresponding author）

11. Zhuang J, Shang Q, Rastinejad F*, Wu D*. Decoding Allosteric Control in Hypoxia-Inducible Factors. J Mol Biol. 2024, 436: 168352.（*co-corresponding author）

10. Li P, Tian Y, Shang Q, Tang C, Hou Z, Li Y, Cao L, Xue S, Bian J, Luo C, Wu D*, Li Z*, Ding H*. Discovery of a highly potent NPAS3 heterodimer inhibitor by covalently modifying ARNT. Bioorg Chem. 2023,139: 106676.（*co-corresponding author）

9. Song W, Zhuang J, Zhang N, Ren X, Xu W, Guo M, Diao X, Liu C, Jin J, Wu D*, Zhang Y*. SAR study of 1,2-benzisothiazole dioxide compounds that agonize HIF-2 stabilization and EPO production. Bioorg Med Chem. 2023, 77: 117041.（*co-corresponding author）

8. Sun X, Jing L, Li F, Zhang M, Diao X, Zhuang J, Rastinejad F, Wu D. Structures of NPAS4-ARNT and NPAS4-ARNT2 heterodimers reveal new dimerization modalities in the bHLH-PAS transcription factor family. Proc Natl Acad Sci USA. 2022, 119: e2208804119.（sole corresponding author）

7. Ren X, Diao X, Zhuang J*, Wu D*. Structural basis for the allosteric inhibition of hypoxia-inducible factor 2 by belzutifan. Mol Pharmacol. 2022, 102: 240-247.（*co-corresponding author）

6. Diao X, Ye F, Zhang M, Ren X, Tian X, Lu J, Sun X, Hou Z, Chen X, Li F, Zhuang J, Ding H, Peng C, Rastinejad F*, Luo C*, Wu D*. Identification of oleoylethanolamide as an endogenous ligand for HIF-3α. Nat Commun. 2022, 13: 2529.（*co-corresponding author）

5. Zhuang J, Liu Q, Wu D*, Tie L*. Current strategies and progress for targeting the "undruggable" transcription factors. Acta Pharmacol Sin. 2022, 43: 2474-2481.（*co-corresponding author）

4. Li F, Song C, Zhang Y, Wu D. Structural overview and perspectives of the nuclear receptors, a major family as the direct targets for small-molecule drugs. Acta Biochim Biophys Sin (Shanghai). 2022, 54: 12-24.（sole corresponding author）[cover story]

3. Wu D*, Su X, Lu J, Li S, Hood BL, Vasile S, Potluri N, Diao X, Kim Y, Khorasanizadeh S, Rastinejad F*. Bidirectional modulation of HIF-2 activity through chemical ligands. Nat Chem Biol. 2019, 15: 367-376. （*co-corresponding author）[F1000Prime recommendation]

2. Smith SH, Jayawickreme C, Rickard DJ, Nicodeme E, Bui T, Simmons C, Coquery CM, Neil J, Pryor WM, Mayhew D, Rajpal DK, Creech K, Furst S, Lee J, Wu D, Rastinejad F, Willson TM, Viviani F, Morris DC, Moore JT, Cote-Sierra J. Tapinarof is a natural AhR agonist that resolves skin inflammation in mice and humans. J Invest Dermatol. 2017, 137: 2110-2119.

1. Wu D, Potluri N, Lu J, Kim Y, Rastinejad F. Structural integration in hypoxia-inducible factors. Nature. 2015, 524: 303-308. [Featured in Nature's concurrent News&Views section，and F1000Prime recommendation]

II.Structure-function studies and drug discovery of other target proteins

5. Li F*, Zhang M, Liu C, Cheng J, Yang Y, Peng X, Li Z, Cai W, Yu H, Wu J, Guo Y, Geng H, Fa Y, Zhang Y, Wu D*, Yin Y*. De novo discovery of a molecular glue-like macrocyclic peptide that induces MCL1 homodimerization. Proc Natl Acad Sci USA. 2025, 122: e2426006122.（*co-corresponding author）

4. Liu J, Sun X, Zhuang J, Liu Z, Xu C, Wu D*, Wu C*. Biphenyl-dihydrothiazole-cyclized peptide libraries for peptide ligand and drug discovery. Sci. China Chem. 2025, 68, https://doi.org/10.1007/s11426-024-2291-x.（*co-corresponding author）

3. Cui J, Liu X, Shang Q, Sun S, Chen S, Dong J, Zhu Y, Liu L, Xia Y, Wang Y, Xiang L, Fan B, Zhan J, Zhou Y, Chen P, Zhao R, Liu X, Xing N*, Wu D*, Shi B*, Zou Y*. Deubiquitination of CDC6 by OTUD6A promotes tumour progression and chemoresistance. Mol Cancer. 2024, 23: 86.（*co-corresponding author）

2. Li F*, Liu J, Liu C, Liu Z, Peng X, Huang Y, Chen X, Sun X, Wang S, Chen W, Xiong D, Diao X, Wang S, Zhuang J, Wu C*,Wu D*. Cyclic peptides discriminate BCL-2 and its clinical mutants from BCL-XL by engaging a single-residue discrepancy. Nat Commun. 2024, 15: 1476.（*co-corresponding author）

1. Xu M, Xu HH, Lin Y, Sun X, Wang LJ, Fang ZP, Su XH, Liang XJ, Hu Y, Liu ZM, Cheng Y, Wei Y, Li J, Li L, Liu HJ, Cheng Z, Tang N, Peng C, Li T, Liu T, Qiao L, Wu D, Ding YQ, Zhou WJ. LECT2, a ligand for Tie1, plays a crucial role in liver fibrogenesis. Cell. 2019, 178: 1478-1492. [F1000Prime recommendation]

III. Structural analysis of biosynthesis-related enzymes and catalytic mechanism research

4. Chen Y, Jing L, Peng M, Cai C, Shi J, Ge W, Liu Y, Shang Z, Ma J*, Wu D*, Ju J*. Enzymatic insights into the unusual formation of benzolactone and benzopyran in the biosynthesis of spiromarmycin. ACS Catal. 2025, 15: 2809-2821.（*co-corresponding author）

3. Chen X, Zhao H, Wang C, Hamed M, Shang Q, Yang Y, Diao X, Sun X, Hu W, Jiang X, Zhang Y, Hirsch AKH, Wu D*, Zhuang J*. Two natural compounds as potential inhibitors against the Helicobacter pylori and Acinetobacter baumannii IspD enzymes. Int J Antimicrob Agents. 2024, 63: 107160.（*co-corresponding author）

2. Wang X, Chen X, Wang ZJ, Zhuang M, Zhong L, Fu C, Garcia R, Müller R, Zhang Y, Yan J*, Wu D*, Huo L*. Discovery and characterization of a myxobacterial lanthipeptide with unique biosynthetic features and anti-inflammatory activity. J Am Chem Soc. 2023, 145: 16924-16937.（*co-corresponding author）

1. Zhong L, Diao X, Zhang N, Li F, Zhou H, Chen H, Bai X, Ren X, Zhang Y*, Wu D*, Bian X*. Engineering and elucidation of the lipoinitiation process in nonribosomal peptide biosynthesis. Nat Commun. 2021, 12: 296.（*co-corresponding author）[Selected as a spotlight paper in the field of "Organic Chemistry and Chemical Biology"]

·  Academic Adjuncts

Young Editorial Member of Acta Pharmaceutica Sinica B

Editorial Board Member, Marine Life Science and Technology

Member, Biochemical and Molecular Pharmacology Committee, Chinese Society of Pharmacology.

Member, Specialized Committee on Pharmacology of Marine Drugs, Chinese Society of Pharmacology

Member, Intelligent Drug Research Committee, Chinese Pharmaceutical Society (CPS)

Member, Microcirculation Drug Research Committee, Chinese Society of Microcirculation (CSMC)

Member, Comparative Physiology Committee, Chinese Physiological Society

 ·  Awards and Honors

 2024 Excellent Doctoral Dissertation Advisor of Shandong Province

2023 "Excellent Graduate Student Supervisor", Shandong University

2022 "Outstanding Communist Party Member", Shandong University

2021 "Young High-level Talents", Ministry of Education

2020 "Star of Research", Institute of Microbial Technology, Shandong University

2019 "Young Taishan Scholars", Shandong Province

 ·  Contact Information

Email: dlwu@sdu.edu.cn

Tel: 0532-58631508

Address: Shandong University, Qingdao Campus