Dr. Michael M. C. Lai, Professor

Genomics Research Center, Academia Sinica
Phone: 886-2-
E-mail:
Education@Research@Publications


Education

1973, Ph.D.@Molecular Biology
@@@@@@ University of California, Berkeley, USA


Research

@The primary research interests of our laboratory are the studies of the mechanisms of replication and pathogenesis of several medically important RNA viruses. Our current interest is on three different viruses:

1. Coronavirus: This virus family includes the SARS coronavirus, which causes severe acute respiratory syndrome. This virus contains the largest genome among RNA viruses. Our laboratory has previously performed many pioneering studies on the structure and replication of this virus, particularly viral RNA synthesis. We discovered the phenomenon of high-frequency RNA recombination in this virus. We are focusing on understanding the viral and cellular factors involved in the viral RNA replication. In the immediate future, we will focus on studying the properties of gene products and mechanism of pathogenesis of the SARS coronavirus.

2. Hepatitis C virus (HCV): This virus is one of the most common causes of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Our laboratory is interested in understanding the mechanism of viral RNA replication. Currently we are focusing on studying the structure and mechanism of formation of the viral RNA replication complex. We are also investigating the properties of the various viral gene products in order to identify the potential targets for developing antiviral agents. Finally, my laboratory has developed an in vitro cell culture system for this virus based on the in vivo association of HCV with B-cell lymphoma. This culture system allows for the first time the study of the biology of HCV infection. We have found that HCV infection induces DNA breaks and enhances DNA mutation frequencies, thus explaining the mechanism of oncogenesis of this RNA virus. We are further exploring the detailed mechanisms of these virus-induced effects.

3. Hepatitis delta virus (HDV): This virus contains a small (1.7 kb) circular RNA genome, which is unique among animal viruses. It replicates by an RNA-dependent RNA replication mechanism, which is carried out by a cellular enzyme. The dilemma is that the mammalian cells do not have RNA-dependent RNA polymerases. It appears that the cellular DNA-dependent polymerase II and possibly other polymerases, together with a unique viral protein hepatitis delta antigen, are involved in this process. This is a novel aspect of cellular machinery. We are further investigating the precise mechanisms of such a process.

Publications

1. Taylor, D.R., Shi, S. T., Romano, P. R., Barber, G. N. and Lai, M. M. C. (1999). Inhibition of the interferon-inducible protein kinase PKR by hepatitis C virus E2 protein. Science 285:107-110.

2. Sung, V. M.-H., Shimodaira, S., Doughty, A.L., Picchio, G.R., Can, H., Yen, T.-S. B., Lindsay, K.L., Levine, A.M., and Lai, M.M.C. (2003). Establishment of B-cell lymphoma cell lines persistently infected with hepatitis C virus in vivo and in vitro: The apoptotic effects of virus infection. J. Virol. 77:2134-2146.

3. Oh, J.-W., Sheu, G.-T., and Lai, M. M. C. (2000). Template requirement and initiation site selection by hepatitis C virus polymerase on a minimal viral RNA template. J. Biol. Chem. 275:17710-17717.

4. Modahl, L. E., Macnaughton, T. B., Zhu, N., Johnson, D. L. and Lai, M. M. C. (2000). RNA-dependent replication and transcription of hepatitis delta virus RNA involve distinct cellular RNA polymerases. Mol. Cell. Biol. 20:6030-6039.

5. Shi, S. T., Huang, P. Y., Li, H.-P. and Lai, M. M. C., (2000). Heterogeneous nuclear ribonucleoprotein A1 regulates RNA synthesis of a cytoplasmic RNA virus. EMBO J. 19, 4701-4711.

6. Machida, K., Cheng, K., Shimodaira, S., Sung, V. M.-H., Lindsay, K. L., Levine, A. M., Lai, M. Y. and Lai, M. M. C., (2004). Hepatitis C virus induces a mutator phenotype: enhanced mutations of immunoglobulin and proto-oncogenes. Proc. Natl. Acad. Sci. USA 101, 4262-4267.


Members of Laboratory