Innate immune response against intracellular pathogen and its relevance to infectious disease

Infection by RNA viruses, such as hepatitis C virus, influenza virus, or MERS-CoV is a severe threat to public health worldwide. Due to the instability of RNA viral genomes, resistant viral strains have frequently arisen, and as a result, it is always big challenge to develop efficient therapeutic drugs or vaccines against them. To overcome this problem, we propose utilization of the host defense machinery against infection.

1)	Mammalian cells install various extracellular, as well as intracellular defense machineries that sense the infection, signal the danger signal to neighboring cells, and block the spreading of pathogens. In addition to specialized immune cells, infected non-immune cells (including epithelial cells and hepatocytes) also play essential roles in the elimination of virus, mainly via production of type I interferons (IFN)s. We are specifically interested in the feedback regulation of cytosolic RIG-I-like Receptor-IFN signaling pathways that sense intracellular virus infection, and the IFN stimulated anti-viral cellular responses that clear infection.
2)	Mitochondria functions as the master controlling center of the intracellular infection. It provides intracellular membranous structure that serves as platform for the assembly of anti-viral signaling complex, and as a major source for danger signal, by generating mtDNA, ROS, and mt-peptide that induce cell-intrinsic danger response. It also physically contacts and communicates with neighboring organelles, like endoplasmic reticulum (ER), to control cellular responses. We aim to understand molecular and physiological aspects of mitochondria and its network with other organelle such as ER-mitochondria, or ER-autophagosome, in the regulation of cellular response against intracellular infection.
3)	Virus infection is initiated by attachment to cell membrane, followed by endocytosis. We are investigating extracellular proteoglycan that functions as an antiviral. Understanding the molecular mechanism of proteoglycan in the regulation of virus infection and development of antivirals utilizing this pathway is currently ongoing in the lab.
4)	Cell senses wide variety of intracellular and extracellular stresses, which are originated from biological, chemical and even physical sources. Among them, mechanical forces at the cell surface can be translated into the chemical signals by cellular machinery controlling mechano-transduction. It regulates variety of cellular process such as proliferation, differentiation and tissue organization. We are currently investigating the molecular mechanism and physiological relevance of mechano-transduction in the regulation of infection and immunity.