Faculty & Research
Indiana Molecular Biology Institute
- Contact Information
- Contact Milton Taylor by taymil [at] indiana [dot] edu
- By telephone: 812-855-3340
- By fax: 812-855-6705
- SI 220D
- Research Areas
- Genomics and Bioinformatics
- Microbial Interactions and Pathogenesis
B.S. Cornell University, 1961
Ph.D., Stanford University, 1966
Fogarty International Fellowship, 1973-74. London, England
Visiting Fellow, Sapienza University, Rome Italy 1980-81
Visiting Fellow , Weizmann Instiatue of Science, 1981-2
Infection with hepatitis. Hepatitis C virus (HCV) is a positive stranded RNA virus and a member of the Flaviviridae family. The virion consists of a nucleo-capsid core (C) and two envelope proteins E1 and E2. At least six non-structural proteins (NS) are involved in transcription, replication and protein processing. The majority of Hep C HCV cases are chronic infections, a minority of which result in cirrhosis of the liver, and possibly hepatic liver cancer.
The only known treatment for hep atitisC is treatment with interferon-alpha (IFN), or more recently combination treatment of IFN-á and the anti-viral drug ribavirin. We have examined the response to interferon-alpha and riabvirin in two groups of patients, Caucasian and Afro-Americans. This was aprt of a large study involving 400 patients at multiple centers. The rate of positive response to treatment is much higher in Caucasian patients(50%) than in African Americans ( 0%) . In general those patients responding to treatment showed higher levels of gene induction after interferon treatment suggesting a defect overall in gene induction in non-responders. This has been termed blunting.The mechanism leading to this sustained response and the lack of response in other patients is not understood. There are several factors involved in response, including age, viral genotype, degree of liver fibrosis , initial levels of HCV and more recently genetic polymorphisms.. In order to study this phenomenon in depth we ran approximately 400 DNA microarrays, measuring the expression of approxiamtely 20,000 genes at multiple time points. This study has been completed and is known as the Virahep C study. A second study with a smaller number of patients using a different interferon gave similar results.
Virus and Human history. Since retiring I have been concentrating on writing a book on the influence of viruses on human history and also a history of virology.
- M W. Taylor, T Tsukahara, L Brodsky, J Schaley, C Sanda, M J. Stephens, J N. McClintick, HJ. Edenberg, L Li, J E Tavis, C Howell, S. H. Belle. 2007. Changes in gene expression during peginterferon and ribavirin therapy of chronic hepatitis C distinguish responders from non responders to antiviral therapy. J. Virology 81(7) 3391-401.
- M J. Donlin, N.A. Cannon, E Yao, , J Li, A. Wahed, M.W Taylor, S.H. Belle A M. Di Bisceglie, R Aurora, and J E. Tavis. 2007. Pretreatment sequence diversity in the full-length Hepatitis C Virus open reading frame correlate with early response to therapy. J. Virology 81(15):8211-24.
- L. I. Brodsky, A.S.Wahed, J. Li, J.E. Tavis, T. Tsukahara and M.W. Taylor. 2007. A Novel Unsupervised Method to Identify Genes Important in the anti-viral Response: application to Interferon/Ribavirin in Hepatitis C Patients PLoS. ONE 4; 2(7):e584.
- Sanda C., Weitzel P, Tsukahara T., Schaley J., Edenberg H.J., Stephens M.A., McClintick J.N., BLatt L.M. Li L, Brodsky L.I, Taylor M.W. 2006. Differential gene induction by type I and type II interferons and their combination. J. Interferon Cytokine Research. 26 462-7.
- Liu, Y., Taylor M.W. Edenberg H.J. Model-based identification of cis-acting elements from Microarray Data., Genomics. May 20, 2006. ( Epub)
- Tsukahara T., Kim S., Taylor M.W. 2006. Refinement: a search framework for the identification of interferon-responsive elements in DNA sequences-a case study with ISRE and GAS. Computational Biology and Chemistry 30, 134-47.
- Tan, H., Derrick J., Hong J., Sanda C., Grosse W.M., Edenberg H.J. Taylor M.W. Seiwart S., Blatt L.M. 2005. Global transcription profiling demonstrates the combination of type I and type II interferon enhances antiviral and immune responses at clinically relevant doses. J. Interferon and Cytokine Res. 25.
- Taylor, M.W, Grosse W.M. Schaley J.E., Sanda C., Wu X., Chen S.C., Smith F., Wu T.G., Stephens M., Ferris M.W., McClintick J.N., Jerome R.E., Edenberg H.J. 2004. Global effect of Peg-IFN-a and ribavirin on gene expression in PBMC in vitro. J. IFN and Cytokine Research 24.
- Kim K.Y. and Taylor M.W. 2003. Identification of a Novel promoter in the E2 open reading frame of the human papillomavirus Type 18 Genome. Journal of Medical Virology 69:122-31.
- Cotler S.J., Reddy R.K., McCone W., Wolfe D.L., Liu A., Craft T, Conrad A., Morrisey M., Ganger D.R., Rosenblate H., Blatt L.M., Jensen D.M. and Taylor M.W. 2001. An analysis of acute IL-6 production in hepatitis C patients treated with IFN-con 1. J. IFN and Cytokine Research 21:1011-19. [article]