Our research focuses on diverse cellular processes, including endocytic pathway, intracellular trafficking of proteins and membranes, membrane organization, nanomaterial traffic, and nanomaterial-mediated global gene expression pattern changes.
Intracellular trafficking pathways are imperative and dysregulation of these traffics are directly associated with multiple human disorders. It has been known that suboptimal endocytosis of LDL (Low Density Lipoprotein-bad cholesterol) or an inefficient recycling of LDL receptor is implicated in atherosclerosis. Inappropriate transport or trafficking of membrane components, including lipids and proteins, between membrane-bound organelles are associated with onset of Alzheimer’s disease and other human diseases. Understanding these trafficking processes has been a major focus of cell biology for several decades. Accordingly, the Nobel Prize in Physiology and Medicine in 2014 was awarded to Dr. James E. Rothman, Dr. Randy W. Schekman and Dr. Thomas C. Südhof for their ground-breaking research concerning the regulation of inner cell protein/membrane traffic in eukaryotic cells.
The budding yeast, Saccharomyces cerevisiae, is a eukaryotic unicellular organism that harbors conserved traffic pathways. Its reproduction cycle is completed within 2 hours, and therefore many researchers have used yeast as their experimental organism for the study of intracellular trafficking. Results obtained from yeast are broadly applicable to higher eukaryotic systems.
Dynamin, which is a GTPase implicated in membrane-pinching off activity and is essential for membrane trafficking of endocytosis and secretory pathways. Our lab has found yeast dynamin-like protein Vps1 plays roles in those traffics, and recently we characterized that Vps1 physically interacts with a recycling factor and a late endosome marker, as well as with a membrane coat protein. We are currently working on the physiological significance of these interactions in recycling and endocytic degradation traffics. We will further elucidate a regulatory role of Vps1 on coat protein assembly at the Golgi.
We also recently found that lipid imbalance in the cell leads to a defect in protein recycling. It appears that proper lipid levels are required for maintenance of intact actin cytoskeleton highway system along which protein trafficking occurs. We are interested in identifying and characterizing motor proteins that carry protein cargo-laden vesicles, moving along the actin system.
The plasma membrane of a cell plays essential roles in protecting and organizing cells. Lines of evidence suggest that the membrane is compartmentalized into microdomains, each of which consists of different protein and lipid composition. The spatiotemporal organization and physiological functions of these microdomains is a hot topic in cell biology. The current paradigm in this field focuses on interdependency between microdomains. Accordingly, studies of functional connection between different microdomains via protein-protein have become standard in this field. My research interest focuses on MCC (Microdomain Containing Can1), which associates with a cytosolic protein complex called eisosome, whose primary organizer is Pil1. Eisosome was introduced in 2006 and its physiological roles are poorly understood, and so we are quite interested in identifying and characterizing Pil1 binding proteins using yeast two hybrid library system, hoping to find out some factors associated with other microdomains.
Finally, we have been testing the potential cytotoxicity of nanoparticles (carbon nanotubes, sliver, and cadmium) on fungal cells. We have recently worked on the effects of these nanoparticles on gene expression pattern, using a high-end DNA sequencer. We plan to measure relative abundance of mRNA sequences in nanoparticle-treated cells and validate the data with qPCR in the near future.