Research Projects

　　　　Phospholipase A₂ (PLA₂) is an enzyme that hydrolyzes glycerophospholipid, a major component of the cell membrane, at the sn-2 position and produces lyso phospholipid and free fatty acid. Since a variety of fatty acids, precursors of bioactive lipids and lipid mediators, are esterified at the sn-2 position, PLA₂ is involved in many biological activities. PLA₂ constitutes a superfamily of enzymes, and each PLA₂ plays a specific role depending on its expression, localization, regulation, and substrate specificity. Therefore, understanding the molecular basis of their characteristics is critical for understanding related biological functions and diseases. Recently, our group has been especially interested in the molecular basis of the enzymatic action and regulation of group VI calcium-independent PLA₂ which is the cause of various neurodegeneration disease (GVIA iPLA₂, PLA₂G6, iPLA₂β, or PNPLA9) and its relationship to neuronal diseases. To address our question, we are taking advantage of computational and structural approaches in addition to traditional biological and molecular biological approaches. We believe that our research leads to finding novel therapeutic approaches and creating potent drugable compounds. Our cuurent research interests are as follows.

• The molecular basis of the enzymatic action and regulation of GVIA PLA₂s

• Role of GVIA PLA₂s in neuron cells

• The phisiological role of alternative splicing and post transcriptional modification of GVIA iPLA₂

• Developping specific inhibitor or activator of GVIA PLA₂

　　　　Ribosomal protein SA (RPSA) is a unique bifunctional protein that is not only a component of a small subunit of the ribosome but also a cell surface nonintegrin type laminin receptor. In addition to laminin, green tea polyphenols, sindbis virus, prion protein, and vitamin E are known to be the ligands of RPSA. RPSA expression is correlated to tumor progression and is an attractive therapeutic target. However, how RPSA alternates its function as a component of the ribosome or a receptor is still enigmatic. To address this question, we focused on plant RPSA, which is highly homologous to human RPSA, and its function has not been described. We believe that we can better understand RPSA by crossing humans to plants. Our current research interest is as follows.

• If and How plant and human RPSA localizes at the plasma membrane.

• If plant RPSA binds to green tea polyphenol or vitamin E, the plant-derived molecules, and their biological role in plans.

• If it is possible to separate the function of RPSA as a receptor and a ribosomal protein.

• Designing the antagonist of RPSA by taking advantage of the binding mode of green tea polyphenol or vitamin E.