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Research Projects Publications

(1) Functions of Akt in cell survival and migration

Akt is a serine/threonine kinase whose activation is often associated with malignant cancers. It has been suggested that Akt promotes tumorigenesis via aberrant promotion of cell survival. We have discovered several targets of Akt in the context of cell survival. For example, Akt phosphorylates and activates Mdm2, a ubiquitin ligase for the tumor suppressor p53, resulting in ubiquitination and degradation of p53. Since p53 is responsible for DNA damage-induced apoptosis, Akt activation makes cells resistant to DNA damage. We also found that Akt is prerequisite for growth factor-stimulated migration of fibroblasts, which might also account for the tumorigenic activity of Akt. We are investigating the mechanisms by which Akt regulates cell survival and migration.

(2) Regulation of neural cell death and differentiation

During neural development, a large number of cells undergo programmed cell death (apoptosis) to eliminate damaged cells and developmentally unwanted cells. Caspases, a family of cysteine proteases, play a central role in induction of apoptosis. Gene disruption of caspase-9 results in exencephaly due to a marked increase of neural precursor cells (NPCs), suggesting the cell death/survival regulation of NPCs is critical for neural development. We are now investigating the signaling pathways regulating NPC survival. Some projects in our laboratory also involve the cell fate regulation during early neural development.

(3) Functions of JNK in cell death regulation

JNK is a member of the stress-activated MAP kinase family, and plays a pivotal role in cell death induced by a variety of cellular stresses. We found that JNK promotes mitochondrial translocation of Bax, a key transducer of apoptotic signaling, resulting in Bax-mediated cytochrome c release from mitochondria. Cytochrome c, in turn, activates the caspase cascade leading to apoptosis. We focus on two projects concerning the functions of JNK in cell death regulation; (I) the mechanisms by which JNK promotes Bax translocation to mitochondria, and (II) the roles and mechanisms of JNK-dependent cell death during neural development. We are also investigating other roles of JNK in neural cells.



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