Xiang Chen, Ph.D.

Xiang Chen, Ph.D.
Staff Scientist

Team Member of:

Xiang Chen uses biophysical techniques to study how proteins are targeted for degradation. He has used NMR spectroscopy to solve the structures of the Rpn13:ubiquitin complex and of full-length hRpn13. The hRpn13 ubiquitin- and Uch37-binding domains interact, which weakens hRpn13 affinity for ubiquitin. Binding to the proteasome abrogates this interaction which, in turn, activates hRpn13 for ubiquitin. Xiang has also used NMR and mass spectroscopy to study how small molecules interact with hRpn13 to inhibit proteasome function.

Areas of Expertise
1) NMR spectoscopy, 2) structural biology, 3) computer modeling of protein structures and complexes, 4) protein engineering and isolation

Contact Info

Xiang Chen, Ph.D.
Center for Cancer Research
National Cancer Institute
Advanced Technology Research Facility (ATRF)/B3330
Frederick, MD 21702-1201
Ph: 301-846-7396
xiang.chen@nih.gov
Dr. Chen’s longstanding research interest is studying the mechanism of how the proteasome recognizes and processes its substrate by using various biophysical techniques, including NMR, mass spectroscopy, and computer modeling. The ubiquitin-proteasome pathway is important to human health as this process regulates protein quality control, transcription, apoptosis, DNA repair, immune response and cell cycle control. The malfunction of the ubiquitin-proteasome pathway is associated with neurological disorders, inflammatory processes and cancer. By using NMR, he has contributed to the discovery of Rpn13 and Rpn1 as substrate receptors in the proteasome. Ubiquitin chains of diverse linkage type can be used to signal for protein degradation by the proteasome and he has dissected the ubiquitin chain preferences of these ubiquitin receptors by using pull-down assays. He has solved the structure of each of these ubiquitin receptors in complex with various ubiquitin species or their preferred shuttle factors. Moreover, he has used NMR and mass spectroscopy to study how small molecules interact with hRpn13 to inhibit proteasome function.
 
Scientific Focus Areas:
Structural Biology

Selected Key Publications

  1. Chen X.*, Randles L.*, Shi K., Tarasov, S.G., Aihara, H., Walters K.J. (Co-first author)
    Structure. 24: 1257-1270, 2016. [ Journal Article ]
  2. Shi Y.*, Chen X.*, Elsasser S.*, Stocks B.*, Tian G., Lee B.H., Shi Y.H., Zhang N.X., de Poot S.A.H., Tuebing F., Sun S.W., Vannoy J., Tarasov S.G., Engen J.R., Finley D., Walters K.J. (Co-first author)
    Science. 351: In press, 2016. [ Journal Article ]
  3. Chen X., Lee B.H., Finley D., Walters K.J.
    Mol Cell. 38: 404-415, 2010. [ Journal Article ]
  4. Chen X., Solomon W.C., Kang Y., Cerda-Maira F., Darwin K.H., Walters K.J.
    J Mol Biol. 392: 208-217, 2009. [ Journal Article ]
  5. Schreiner P.*, Chen X.*, Husnjak K.*, Randles L., Zhang N.X., Elsasser S., Finley D., Dikic I., Walters K.J., Groll M. (Co-first author)
    Nature. 453: 548-552, 2008. [ Journal Article ]
Dr. Chen received his Ph. D. from Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences and his graduate work was about the structure/function studies of scorpion toxin peptides. In 2005, he joined Dr. Kylie Walters’ group at University of Minnesota as a postdoctoral associate, and started to study the ubiquitin-proteasome system by using NMR. In 2013 he moved to Maryland and became a research fellow in Protein Processing Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute. In 2016, he was promoted to be a Staff Scientist.