Our laboratory is focusing on the intracellular calcium (Ca2+)- dependent signal transduction system. We are studying the structure and function of protein kinases and developing protein kinase inhibitors. Furthermore, based on the mechanism of the immune system, we have developed new technologies for antibody production.

Introduction to Projects

Structure and Function of Camlodulin-dependent Protein Kinases

Ca2+/calmodulin-dependent protein kinase kinases (CaMKKs) were originally identified as a member of the calmodulin (CaM) kinase (CaMK) family, which phosphorylate and activate AMPK and two multifunctional CaMKs including CaMKI and CaMKIV, constituting Ca2+-dependent kinase cascades named CaMK cascades. We have developed a CaMKK inhibitor, STO-609 to evaluate physiological and pathophysiological function(s) of CaMKK-mediated Ca2+-signal transduction. Now, we knew CaMK cascades are involved in various cellular responses including neuronal activity, metabolic regulation and cancer cell growth.

IDevelopment of in vitro Antibody Generation Systems by Elucidating and Modeling on in vivo Mechanisms

Antibodies, which bind to specific antigens with high affinity, are useful as not only reagents for research and diagnosis but also medicines for diseases. Antibody-producing B cells are activated and differentiated into antibody-secreting plasma cells and memory cells in germinal centers in lymphoid tissues. Evolution of antibodies, which are called antibody affinity maturation, also occurs by mutation of antigen-binding sites in antibodies and selection of higher-affinity clones. We have developed an in vitro cell culture system that enables to reconstitute cell-cell interactions in lymphoid tissues, to elucidate antibody generation mechanisms. On the other hand, we have been developing a novel in vitro antibody generation system that is modeled on in vivo antibody generation mechanisms. Generation and improvement of human antibodies and nonconventional antibodies will be also available using this system.