Ning Zheng Explained

Thesis Title:	A Tale of Two Ligands: Signal Sequence Recognition by E. coli Signal Sequence Recognition Particle with its Indispensable RNA Component (1997)
Doctoral Advisor:	Lila M. Gierach
Work Institutions:	University of Washington

Ning Zheng is an experimental structural biologist and protein biochemist known for his pioneering work in the fields of molecular glues and targeted protein degradation. He is currently a professor in the Department of Pharmacology at the University of Washington School of Medicine and a Howard Hughes Medical Institute (HHMI) Investigator.^{[1] [2]}

Education and training

The son of a Chinese biochemistry professor, Ning Zheng obtained his Ph.D. in 1997 from the University of Texas Southwestern Medical Center.^{[3] [4]}

He completed his postdoctoral studies at the Memorial Sloan-Kettering Cancer Center under the mentorship of Nikola Pavletich, where he published two seminal studies on the atomic structures of prototypical human ubiquitin ligase complexes.^{[5] [6]} These studies laid the foundation for his subsequent research and contributions to structural biology and protein ubiquitination.

Research

Ning Zheng’s research focuses on the molecular and structural mechanisms by which protein-protein interactions regulate eukaryotic biology and human diseases. His laboratory has made significant contributions to understanding the cullin-RING superfamily of E3 ubiquitin ligases, which is implicated in a myriad of cellular functions such as signal transduction, cell cycle regulation, transcriptional control, and DNA repair.^[7]

Zheng's recent studies have expanded to several areas of life sciences, including protein degradation, plant hormone signaling, circadian clock regulation, chromatin modification, and the structure-function relationships of ion channels and transporters. His groundbreaking work on the perception mechanism of the plant hormone auxin led to the introduction of the concept of "molecular glue."^{[8] [9]} This concept describes how monovalent small molecules can promote protein-protein interactions by complementing protein interfaces, facilitating targeted-protein degradation.^[10] This conceptual advance has become instrumental in the development of novel therapeutic compounds for targeting disease-causing proteins considered undruggable.^[11] His laboratory is actively involved in drug discovery programs aimed at treating challenging human diseases, such as cancers and neurodegenerative disorders.

Awards and recognition

Throughout his career, Ning Zheng has received numerous accolades. After joining the faculty of Pharmacology at the University of Washington, he was awarded the Pew Scholar Award and the Burroughs Welcome Investigator Award in Pathogenesis of Infectious Diseases.^{[12] [13]} In 2008, he became a Howard Hughes Medical Institute Investigator.^[2] He was promoted to Professor in 2012.^[14] His significant contributions to science have been recognized through his election as a Fellow of the American Association for the Advancement of Science (AAAS) in 2015 and as a member of the Washington State Academy of Science in 2020.^{[15] [16]}

Selected publications

• Cao, S., Kang, S., Mao, H. et al. Defining molecular glues with a dual-nanobody cannabidiol sensor. Nat Commun 13, 815 (2022). https://doi.org/10.1038/s41467-022-28507-1
• Sheard, L., Tan, X., Mao, H. et al. Jasmonate perception by inositol-phosphate-potentiated COI1–JAZ co-receptor. Nature 468, 400–405 (2010). https://doi.org/10.1038/nature09430
• Tan, X., Calderon-Villalobos, L., Sharon, M. et al. Mechanism of auxin perception by the TIR1 ubiquitin ligase. Nature 446, 640–645 (2007). https://doi.org/10.1038/nature05731
• Angers, S., Li, T., Yi, X. et al. Molecular architecture and assembly of the DDB1–CUL4A ubiquitin ligase machinery. Nature 443, 590–593 (2006). https://doi.org/10.1038/nature05175
• Goldenberg, S.J., Cascio, T.C., Shumway, S.D. et al. Structure of the Cand1-Cul1-Roc1 complex reveals regulatory mechanisms for the assembly of the multisubunit cullin-dependent ubiquitin ligases. Cell, 12;119(4):517-28. (2004). https://doi.org/10.1016/j.cell.2004.10.019
• Zheng, N., Schulman, B., Song, L. et al. Structure of the Cul1–Rbx1–Skp1–F boxSkp2 SCF ubiquitin ligase complex. Nature 416, 703–709 (2002). https://doi.org/10.1038/416703a

External links

• University of Washington faculty page
• Howard Hughes Medical Institute profile
• Lab website

Notes and References

1. Web site: Ning Zheng . 2024-05-24 . UW Pharmacology . en-US.
2. Web site: Ning Zheng, PhD Investigator Profile 2008-Present . 2024-05-24 . www.hhmi.org . en.
3. April 2007 . Ning Zheng : How an e-mail got a structural biologist hooked on plants. . Nature . en . 446 . 7136 . xiii–xiii . 10.1038/7136xiiia . 1476-4687.
4. Web site: Dr. Ning Zheng Bio – Chinese Institute of Engineers (Seattle Chapter) . 2024-06-21 . en-US.
5. Zheng . Ning . Schulman . Brenda A. . Song . Langzhou . Miller . Julie J. . Jeffrey . Philip D. . Wang . Ping . Chu . Claire . Koepp . Deanna M. . Elledge . Stephen J. . Pagano . Michele . Conaway . Ronald C. . Conaway . Joan W. . Harper . J. Wade . Pavletich . Nikola P. . April 2002 . Structure of the Cul1–Rbx1–Skp1–F boxSkp2 SCF ubiquitin ligase complex . Nature . en . 416 . 6882 . 703–709 . 10.1038/416703a . 11961546 . 1476-4687.
6. Goldenberg . Seth J. . Cascio . Thomas C. . Shumway . Stuart D. . Garbutt . Kenneth C. . Liu . Jidong . Xiong . Yue . Zheng . Ning . November 2004 . Structure of the Cand1-Cul1-Roc1 Complex Reveals Regulatory Mechanisms for the Assembly of the Multisubunit Cullin-Dependent Ubiquitin Ligases . Cell . 119 . 4 . 517–528 . 10.1016/j.cell.2004.10.019 . 15537541 . 0092-8674.
7. Web site: Ning Zheng Laboratory at the University of Washington . 2024-05-24 . depts.washington.edu.
8. Tan . Xu . Calderon-Villalobos . Luz Irina A. . Sharon . Michal . Zheng . Changxue . Robinson . Carol V. . Estelle . Mark . Zheng . Ning . 2007-04-05 . Mechanism of auxin perception by the TIR1 ubiquitin ligase . Nature . 446 . 7136 . 640–645 . 10.1038/nature05731 . 1476-4687 . 17410169. 2007Natur.446..640T .
9. Garber . Ken. 2024-03-06 . The glue degraders . Nature Biotechnology . 42 . 4 . 546–550. 10.1038/s41587-024-02164-9 . 38448663 .
10. Molecular glue binds protein degradation experts together . Nature . en.
11. Garber . Ken . 2024-04-01 . The glue degraders . Nature Biotechnology . en . 42 . 4 . 546–550 . 10.1038/s41587-024-02164-9 . 38448663 . 1546-1696.
12. Web site: Pew Biomedical Scholars .
13. Web site: Grant Recipients . 2024-05-24 . Burroughs Wellcome Fund . en-US.
14. Web site: Participating Faculty . 2024-05-25 . UW Biological Physics, Structure and Design . en-US.
15. Web site: AAAS names four UW researchers as fellows . 2024-05-24 . UW News . en.
16. Web site: 7 University of Washington researchers elected to the Washington State Academy of Sciences in 2020 . 2024-05-24 . UW News . en.