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.