Oncology (affiliate graduate school)

Approximately 15% of all human cancers are considered to have a viral etiology, but only six viruses have actually been implicated in their development. Among these the Epstein-Barr virus (EBV), a gamma herpesvirus associated with several malignant diseases, is the main object of our own study. Our research aims are to elucidate the molecular mechanisms of viral proliferation and oncogenesis of EBV and to control EBV positive tumors. Also, we are interested in the studies for proteoglycan and sphingolipids that regulate apoptpsis of cancer cells, leading to the development of novel drugs for cancer treatment.

(1) EBV genome DNA replication. EBV DNA is synthesized by EBV replication machinery in localized sites of infected nuclei, called replication compartments. We have characterized these replication proteins biochemically to develop anti-viral drugs.

(2) Host cellular responses accompanied by EBV replication. We have found that the EBV productive replication elicited activation of ATM-dependent DNA damage signaling. However, p53-downstream signaling was blocked through the interaction between p53 and the BZLF1 protein. Also, chromosomal DNA replication was prevented through the phosphorylation of the MCM complex by EBV encoded protein kinase.

(3) Virus engineering. We have constructed recombinant HCMV and EBV mutants using BAC (bacterial artificial chromosome) system. With these mutants we are studying about the functions of viral proteins and genome, developing attenuated vaccine and applying for virotherapy.

(4) Studies for Proteoglycan and Sphingolipids regulating Cancer cells. We are aimed to develop novel anti-cancer drugs through characterization of Proteoglycan and Sphingolipids.