Michael M.C. Lai , M.D., Ph.D. Distinguished Emeritus Professor Dr. Lai is a Distinguished Professor of Molecular Microbiology and Immunology at the University of Southern California Keck School of Medicine, Los Angeles. He earned his M.D. degree from National Taiwan University. He studied retroviruses with Peter Duesberg at the University of California, Berkeley, where he earned his Ph.D. degree in molecular biology and continued for postdoctoral work.
Dr. Lai is interested in understanding the molecular basis of neuropathogenesis of murine coronaviruses as a basis for understanding virus-induced demyelination. (Murine coronavirus infection is an animal model for multiple sclerosis. Many virus variants which differ in the ability to cause neurological symptoms have been identified.) Molecular biology approaches are currently being used to determine which viral genes are responsible for the neuropathogenicity of viruses. Studies of the regulation of gene expression, its effects on the virus, and its associated neurological diseases are ongoing. Research Interests
The main interest of our laboratory is the study of the molecular biology and pathogenesis of hepatitis C virus, hepatitis delta virus, and murine coronavirus particularly focusing on the structure and replication of viruses and virus-host interactions with relevance to the mechanism of virus-induced diseases.
Hepatitis C virus. This causes mostly chronic infections and is the most prevalent form of hepatitis in the U.S. We study the regulation of viral RNA replication and translation. We also investigate the mechanism of viral escape from interferon, and the mechanism of viral persisence. We are examining the interaction between viral proteins and cytokines. The eventual goals of these projects are to develop better strategy for HCV therapy.
Hepatitis delta virus. The virus converts cellular polymerases into RNA-dependent polymerases. We are utilizing a novel strategy developed in our laboratory to study this unique mechanism of RNA-dependent RNA transcription and replication. We are also studying the structure and fucntions of ribozymes associated with this viral RNA.
Coronaviruses. Our laboratory has discovered a novel discontinuous RNA transcription mechanism for this virus. We are characterizing the viral and cellular proteins involved in the RNA transcription, particularly focusing on RNA-protein and protein-protein interactions. This virus is being used as a model for understanding the roles of cellular factors in viral RNA synthesis.
Degrees
University of California, Berkeley, Ph.D.:, 1973
National Taiwan University College, M.D., 1968
Fellowships
University of California, Berkeley, 2000 - 1973
Li, H.-P., Zhang, X., Comai, L., Duncan, R., and Lai, M.M.C. (1997) Heterogeneous nuclear ribonucleoprotein A1 binds to the transcription-regulatory region of mouse hepatitis virus RNA. Proc. Natl. Acad. Sci USA 94:9544-9549.
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 HCV E2 protein. Science 285:107-110.
Ito, T., Tahara, S.M., and Lai, M.M.C. (1998) The 3'-untranslated region of hepatitis C virus RNA enhances translation from an internal ribosomal entry site. J. Virol. 72:8789-8796.
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.
Shi, S.T., Huang, P.Y., Li, H.P. and Lai, M.M.C. (2000). Heterogenous nucelar ribonucleoprotein A1 regulates RNA synthesis of a cytoplasmic virus. EMBO J. 19:4701-4711.
Macnaughton TB, Lai MM. Large hepatitis delta antigen is not a suppressor of hepatitis delta virus RNA synthesis once RNA replication is established. J Virol. [ 2002 ] Oct;76(19):9910-9.
Lai MM, Haller JA. Resolution of epithelial ingrowth in a patient treated with 5-fluorouracil. Am J Ophthalmol. [ 2002 ] Apr;133(4):562-4.
Koev G, Duncan RF, Lai MM. Hepatitis C virus IRES-dependent translation is insensitive to an eIF2alpha-independent mechanism of inhibition by interferon in hepatocyte cell lines. Virology. [ 2002 ] Jun 5;297(2):195-202.
Macnaughton TB, Lai MM. Genomic but not antigenomic hepatitis delta virus RNA is preferentially exported from the nucleus immediately after synthesis and processing. J Virol. [ 2002 ] Apr;76(8):3928-35.
Shi ST, Polyak SJ, Tu H, Taylor DR, Gretch DR, Lai MM. Hepatitis C virus NS5A colocalizes with the core protein on lipid droplets and interacts with apolipoproteins. Virology. [ 2002 ] Jan 20;292(2):198-210.
Macnaughton TB, Shi ST, Modahl LE, Lai MM. Rolling circle replication of hepatitis delta virus RNA is carried out by two different cellular RNA polymerases. J Virol. [ 2002 ] Apr;76(8):3920-7.
Lai MM. Hepatitis C virus proteins: direct link to hepatic oxidative stress, steatosis, carcinogenesis and more. Gastroenterology. [ 2002 ] Feb;122(2):568-71. Review.
Pavio N, Taylor DR, Lai MM. Detection of a novel unglycosylated form of hepatitis C virus E2 envelope protein that is located in the cytosol and interacts with PKR. J Virol. [ 2002 ] Feb;76(3):1265-72.
Park KJ, Choi SH, Lee SY, Hwang SB, Lai MM. Nonstructural 5A protein of hepatitis C virus modulates tumor necrosis factor alpha-stimulated nuclear factor kappa B activation. J Biol Chem. [2002 ] Apr 12;277(15):13122-8.
Liu ZX, Nishida H, He JW, Lai MM, Feng N, Dennert G. Hepatitis C virus genotype 1b core protein does not exert immunomodulatory effects on virus-induced cellular immunity. J Virol. [ 2002 ] Feb;76(3):990-7.
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