1) Search for the genes regulated by STAT3 transcription factor
Embryonic stem cells (ES cells) have a potential to differentiate into any tissues of the body. ES cell requires a cytokine, LIF (leukemia inhibitory factor) to maintain its traits and to proliferate. Without LIF it starts to differentiate into various tissues. Inhibition of differentiation by LIF is a critical event in the regulation of mammalian differentiation. This signal transduction pathway consists of LIF receptor and gp130 receptor. And STAT (signal transducer and activator of transcription) proteins have interesting roles during this process. STATs have two different roles such as signal transducers which are activated by membrane receptors or Jak kinase, and transcription factors which translocate into nucleus and regulate the transcription of specific genes. Based on these facts, our lab are searching for the genes regulated by STAT3 during early developmental stage using ChIP (chromatin immunoprecipitation) method.
2) cAMP-dependent protein kinase and the signal transduction in cancer cells
It has been known that there are two isozymes of protein kinase A, type I and type II, which are distinguished by the association of different regulatory subunits, RI and RII, to common catalytic subunit. The balance of type I and type II PKA is closely related to proliferation, differentiation, and apoptosis of cells, which is critical events in the development and the maintenance of an organism. Through the research performed in this lab, it was found that RI or type I PKA is related to the cell growth and transformation, and RII or type II PKA is involved in the growth inhibition and differentiation.
Recently, we found that various cancer cells show different response toward the treatment of 8-Cl-cAMP, such as growth retardation, differentiation, and apoptosis. We are focusing on the regulatory mechanism involved in the different response of cancer cells to 8-Cl-cAMP. Especially, 8-Cl-cAMP induces apoptotic cell death in neuroblastoma cells but not in normal neuron cells, showing its potential as a selective cancer therapeutic drug. Currently, we are working on the mechanism of 8-Cl-cAMP-induced apoptosis in relation to cell cycle- and apoptosis-regulating proteins.