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Our research interests lie on elucidating how membrane proteins are synthesized, matured, processed and undergo degradation, and what cellular components mediate these processes in the eukaryotic cell. In particular, we investigate these phenomena in cellular systems using S. cerevisiase as a model organism and in the cultured human cells. Currently, our research focuses on studying the roles, actions and regulations of signal peptidase complex (SPC) in biogenesis, quality control and degradation of membrane proteins.     

Secretory and membrane proteins destined for the secretory pathway have N-terminal cleavable signal peptides (SPs) or uncleavable signal-anchor sequences (SAs) that guides them to the Sec61 translocons in the endoplasmic reticulum (ER) membrane in eukaryotes. Upon targeting, both types of signal sequences help initiate co- or post-translational protein translocation across the membrane. While translocons recognize both SPs and SAs, the membrane signal peptidase complex (SPC) recognizes and cleaves off SPs but not SAs. An uncleaved SA sequence becomes a transmembrane segment, thus a protein becomes a membrane protein (Figure, top). Therefore, depending on the action of SPC, the fate and localization of secretory proteins can change. SPC also processes some transmembrane segments of membranes proteins and viral polyproteins, illustrating its role in biogenesis and degradation of membrane and viral proteins (Figure, bottom). However, how SPC selects and distinguish varying types of substrates and how these processes are regulated remain poorly understood, and we attempt to answer to these questions.