Xiang Chen, Ph.D.
- Center for Cancer Research
- National Cancer Institute
- Bldg. 538, Room 166
- Frederick, MD 21702-1201
- 301-846-7396
- xiang.chen@nih.gov
RESEARCH SUMMARY
My research has focused on the regulated destruction of proteins by the ubiquitin–proteasome pathway. As a structural biologist, I have been working on exploring the ubiquitin–proteasome system at the atomic level by using biophysical techniques such as NMR. I have solved the structures of ubiquitin receptors complex with various ubiquitin species or their preferred shuttle factors. I’m also directing my research interest towards expanding my skillset to study larger proteasome complexes that may not be tractable by NMR, by merging my protein chemistry and NMR skills with new skills. One of my jobs is to training and assisting my co-workers by sharing my skill set.
Areas of Expertise
Xiang Chen, Ph.D.
Research
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.
Publications
Structures of Rpn1 T1:Rad23UBL and hRpn13Pru:hLIC2UBL reveal distinct binding mechanisms between substrate receptors and shuttle factors of the proteasome
Rpn1 provides adjacent receptor sites for substrate binding and deubiquitination by the proteasome
Structure of Proteasome Ubiquitin Receptor hRpn13 and its Activation by the Scaffolding Protein hRpn2
Prokaryotic Ubiquitin-Like Protein Pup Is Intrinsically Disordered
Ubiquitin docking at the proteasome via a novel PH domain interaction
Biography
Xiang Chen, Ph.D.
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.