Our research focuses on developing and employing novel mass spectrometry-based proteomic strategies for comprehensive analysis of macromolecular protein complexes to define their composition, heterogeneity, modification, interaction and structure. This is one of the major endeavors in advanced proteomics research as most processes in a cell are mediated by large protein assemblies or multi-protein complexes. We aim to generate a molecular framework that enables better understanding of how “protein machines” function in cells and how they are associated with human pathology. The success of our research will lead to not only technological innovations for advancing the study of protein complexes pertinent to biomedical problems, but importantly new discoveries to help design better strategies for disease prevention, diagnostics and treatment.
Specifically, we are interested in protein complexes (e.g. proteasomes) in the ubiquitin-proteasome system (UPS) as it represents the major pathway for regulated degradation of intracellular proteins in eukaryotes. The UPS helps control and integrate numerous essential physiological processes in cells. Disruption of normal proteasomal degradation leads to a variety of human diseases including cancer and neurodegenerative disorders. Modulation of the UPS has shown great promises in various clinical applications, which represents a powerful but poorly understood new class of therapeutics. To facilitate the development of UPS-dependent therapeutics, it is crucial to understand the interplay between the UPS and human pathology.