Address421 E. Canfield Street, Suite 1146 Detroit, MI 48201
421 E. Canfield Street, Suite 1146
Detroit, MI 48201
• We use both Saccharomyces cerevisiae and mammalian systems to study the pathways that control the degradation of key regulatory proteins.
• We design peptide-based Protacs to target undruggable oncoproteins for proteasomal degradation.
• We develop novel approaches to targeting the proteasome for cancer therapy.
The focus of our research is to understand the molecular mechanisms underlying protein degradation mediated by the ubiquitin-proteasome system (UPS). UPS is the primary intracellular machine responsible for elimination of abnormal proteins and selective destruction of regulatory proteins involved in a wide range of cellular processes including cell cycle control, DNA transcription, replication and repair, and stress response. Dysregulation of UPS is implicated in various human diseases including cancer. Moreover, UPS has now become an important target for anti-cancer therapy. We use both Saccharomyces cerevisiae and mammalian systems to define the pathways that control the degradation of several key regulatory proteins. In addition, we are studying the differential responsees of normal cells and cancer cells to inhibitors of UPS.
Wang H, Ju, D, Kho, D-H, Yang H. Li L, Raz A, Sun F, Xie Y. The ubiquitin specific protease USP34 protects the ubiquitin ligase gp78 from proteasomal degradation. Biochem Biophys Res Commun 2019;509:348-53.
Bao X, Wu J, Xie Y, Kim S, Michelhaugh S, Jiang, J, Mittal S, Sanai N, Li J. Protein expression and functional relevance of efflux and uptake drug transporters at the blood-brain barrier of human brain and glioblastoma. Clin Pharmacol Ther 2019; Oct 30. [Epub ahead of print]
Xia H, Wei, H, Rajagopalan C, Jiang H, Wu T, Zaman K, Xie Y*, Sun F* (Co-Corresponding authors) Dissection of the role of VIMP in endoplasmic reticulum-associated degradation of CFTRΔ508. Scientific Reports 2018;8:4764.
Li J, Wu J, Bao X, Honea N, Xie Y, Kim S, Sparreboom A, Sanai N. Quantitative and mechanistic understanding of AZD1775 penetration across human blood-brain barrier in glioblastoma patients using an IVIVE-PBPK modeling approach. Clin Cancer Res 2017;23:7454-66.
Ha S-W, Ju D, Hao W, Xie Y. Rapidly translated polypeptides are preferred substrates for cotranslational protein degradation. J Biol Chem 2016;291:9827-34.
Xie Y. Feedback regulation of proteasome gene expression and its implications in cancer therapy. Cancer Metastasis Rev 2010;29:687-93.
PhD in Cell Biology (1996): University of Texas, MD Anderson Cancer Center, Houston, Texas
Post-Doc in Biochemistry (1996-2002): California Institute of Technology, Pasadena, California
CB7210 Fundamentals of Cancer Biology (Course Director)
CB7220 Molecular Biology of Cancer Development
CB7300 Special Topics F31 Grant Writing Course