Journal of Developing Drugs
Open Access

Zhe Sha

Biography

Dr. ZheSha got his B.S. degree from the department of Biology at Fudan University. He then did his Ph.D. dissertation at Dr. Eric C. Chang’s laboratory at the Department of Molecular and Cellular Biology and the Lester & Sue Smith Breast Center at Baylor College of Medicine. His Ph.D. dissertation focused on identifying the mechanism by which Int6, a breast tumor suppressor gene, maintains protein homeostasis and genetic stability by promoting proper assembly and localization of the 26S proteasome. After graduation, Dr. Sha joined Professor Alfred L. Goldberg’s laboratory at the Department of Cell Biology at Harvard Medical School to conduct further research in the proteasome and cellular proteolysis area. His current research focuses on identifying cell killing mechanisms by proteasome inhibition, and cellular compensatory responses to promote survival.

Research Interest

Proteasome inhibition is toxic, especially to multiple myeloma cells, and the inhibitor, bortezomib/Velcade, has dramatically improved myeloma treatment. Diminished proteasome function also may contribute to neurodegenerative diseases. Consequently, understanding what consequences of proteasome inhibition causes death in various types of cells, and how different cells compensate for loss of protein degradation capacity in order to promote survival, will be very helpful to improve the Bortezomib therapy, and to pharmaceutically upregulate protein degradation capacity for the benefit of treating neurodegenerative diseases. To this end, I am pursuing two directions: (1) How do cells transcriptionally upregulate components of the ubiquitin-proteasome system and the autophagy-lysosomal system to increase protein degradation capacity; (2) How are proteasome composition (especially the abundance of substochiometric proteasome-binding proteins) and proteasome modifications are altered upon proteasome inhibition to modulate proteasome activity and amplify the inhibitory effect of Bortezomib.