The aims and ongoing research projects in our laboratory are to elucidate molecular mechanisms that underlie the regulation of signal transduction systems, such as “MAP kinase cascades” and “Stress granules”, which are responsible for cell-fate decisions including cell growth, differentiation, and apoptosis.
　The MAPK signaling cascades are well conserved in all eukaryotes and consist of three tiers of protein kinases (MAPKKK-MAPKK-MAPK). In mammals, there are at least three subfamilies of MAPKs, named ERK, JNK and p38. The ERK subfamily members are activated by mitogenic stimuli and are associated with proliferative responses. In contrast, JNK and p38 are activated by environmental stresses (e.g., DNA-damaging reagents, UV irradiation, or osmotic shock) and by cytokines (e.g., TNFα), and are associated with inflammation, reparative, and/or apoptotic responses.
　Stress granules are recently discovered cytoplasmic punctate foci (composed of mRNA and proteins) that appear when the cell is under stress. We have recently identified a novel role of stress granules in the regulation of apoptotic cell death. Formation of stress granules suppresses the activation of p38 and JNK pathways, thereby inhibiting stress-induced apoptosis. However, the precise function of stress-granule formation, particularly its role in the regulation of cellular stress responses, remains to be elucidated.
　Perturbation of these critical signaling systems is involved in a variety of life-threatening diseases, including cancer, autoimmune diseases, neurodegenerative disorders and type 2 diabetes. Therefore, these signaling systems are of clinical importance. Our laboratory also aims to develop new diagnostic and therapeutic tools for currently intractable disorders in which these pathways are involved. Techniques employed in our lab include: molecular and cell biology, biochemistry and genetic engineering (including knockout mice and yeast). For more details regarding our laboratory, please visit our Web site: http://www.ims.u-tokyo.ac.jp/dcsmm/DCSMM/Top-E.html