Dr. Zhubing Shi received his Ph.D. from Tongji University in 2016. In 2010－2018, as a research assistant, visiting Ph.D. student and research associate, he studied the mechanism of macromolecular complexes involved in tumorigenesis and immune regulation at the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. Then he did his postdoctoral training in Dr. Hongtao Yu lab at the University of Texas Southwestern Medical Center in the United States, where he focused on studying the molecular mechanism of chromosome organization. He joined Westlake University as an Assistant Professor and Principal Investigator in September 2021.

The 3D chromosome structure determines DNA replication, recombination and repair, gene expression, and chromosome segregation. A fundamental question in biology is how a long linear genome, e.g., two meters for haploid human genome, is packaged into a micrometer-sized nucleus. A family of revolutionarily conserved Structural Maintenance of Chromosomes (SMC) proteins play pivotal roles in genome topology and chromosome segregation both in prokaryotic and eukaryotic cells. In eukaryotic cells, the SMC complex cohesin shapes chromosome by loop extrusion in vertebrate interphase nuclei and mediates sister chromatid cohesion by topological entrapment in mitosis. Malfunction of cohesin is tightly associated with developmental disorders and tumorigenesis. During postdoctoral training, Dr. Shi made major contributions to deciphering the mechanism of cohesin in DNA transaction. His work revealed the mechanism of cohesin activation and DNA loading, and testified the loop extrusion model, by which chromatin is compacted to topologically associating domains (TADs) and loops (Science, 2019; Science, 2020).

The chromosome structure and gene expression are tightly coupled. Chromatin domains create a microenvironment to restrain gene transcription within domains but also promote gene expression by facilitating interactions between cis-regulatory elements. Gene transcription, in turn, enhances the contacts within domains and thus drives the formation of high-order structures of genome both locally and globally. Histone, DNA and RNA modifications are also widely involved in genome organization and gene expression regulation. Dr. Shi’s lab applies biochemical, structural, biophysical, and cellular methods to explore the principles and mechanisms of chromosome organization, gene transcription and especially, their interplay. Dysregulation of genome structure and aberration of gene expression will lead to developmental disorders and cancers. The work in Dr. Shi’s lab will help understand the causes of related diseases.

Chromosome structure and gene expression regulation 

(* equal contribution)

1. Zhang H*, Shi Z*, Kim Y, Yu H, Bai X, Finkelstein IJ (2022). CTCF and R-loops are boundaries of cohesin-mediated DNA looping. bioRxiv: 2022.2009.2015.508177.

2. Kaur P, Shi Z, Lu X, Zhang H, Finkelstein IJ, Tao YJ, Yu H, Wang H (2022). DNA capture and loop extrusion dynamics by cohesin-NIPBL. bioRxiv: 2022.2008.2018.504320.

3. Shi Z, Gao H, Bai XC, Yu H (2020). Cryo-EM structure of the human cohesin–NIPBL–DNA complex. Science 368(6498): 1454-1459. (Recommendations in Faculty Opinions)

4. Kim Y*, Shi Z*, Zhang H, Finkelstein IJ, Yu H (2019). Human cohesin compacts DNA by loop extrusion. Science 366(6471): 1345-1349. (Recommendations in Faculty Opinions)

5. Shi Z*, He F*, Chen M, Hua L, Wang W, Jiao S, Zhou Z (2017). DNA-binding mechanism of the Hippo pathway transcription factor TEAD4. Oncogene 36(30): 4362-4369.

6. Shi Z, Jiao S, Zhou Z (2016). STRIPAK complexes in cell signaling and cancer. Oncogene 35(35): 4549-4557. (Review)

7. Hao Q*, Jiao S*, Shi Z*, Li C, Meng X, Zhang Z, Wang Y, Song X, Wang W, Zhang R, Zhao Y, Wong CC, Zhou Z (2015). A non-canonical role of the p97 complex in RIG-I antiviral signaling. EMBO J 34(23): 2903-2920.

8. Shi Z, Zhang Z, Zhang Z, Wang Y, Li C, Wang X, He F, Sun L, Jiao S, Shi W, Zhou Z (2015). Structural insights into mitochondrial antiviral-signaling protein (MAVS)-tumor necrosis factor receptor-associated factor 6 (TRAF6) signaling. J Biol Chem 290(44): 26811-26820.

9. Shi Z, Jiao S, Zhou Z (2015). Structural dissection of Hippo signaling. Acta Biochim Biophys Sin 47(1): 29-38. (Review)

10. Chen C^*, Shi Z^*, Zhang W, Chen M, He F, Zhang Z, Wang Y, Feng M, Wang W, Zhao Y, Brown JH, Jiao S, Zhou Z (2014). Striatins contain a noncanonical coiled coil that binds protein phosphatase 2A A subunit to form a 2:2 heterotetrameric core of striatin-interacting phosphatase and kinase (STRIPAK) complex. J Biol Chem 289(14): 9651-9661.

11. Jiao S*, Wang H*, Shi Z*, Dong A, Zhang W, Song X, He F, Wang Y, Zhang Z, Wang W, Wang X, Guo T, Li P, Zhao Y, Ji H, Zhang L, Zhou Z (2014). A peptide mimicking VGLL4 function acts as a YAP antagonist therapy against gastric cancer. Cancer Cell 25(2): 166-180.

12. Zhang M*, Dong L*, Shi Z*, Jiao S*, Zhang Z, Zhang W, Liu G, Chen C, Feng M, Hao Q, Wang W, Yin M, Zhao Y, Zhang L, Zhou Z (2013). Structural mechanism of CCM3 heterodimerization with GCKIII kinases. Structure 21(4): 680-688.

13. Shi Z*, Jiao S*, Zhang Z*, Ma M, Zhang Z, Chen C, Wang K, Wang H, Wang W, Zhang L, Zhao Y, Zhou Z (2013). Structure of the MST4 in complex with MO25 provides insights into its activation mechanism. Structure 21(3): 449-461.

14. Wang W*, Shi Z*, Jiao S*, Chen C, Wang H, Liu G, Wang Q, Zhao Y, Greene MI, Zhou Z (2012). Structural insights into SUN-KASH complexes across the nuclear envelope. Cell Res 22(10): 1440-1452.

Full Publication List: https://scholar.google.com/citations?hl=en&user=qNpEU08AAAAJ

shizhubing@westlake.edu.cn