Professor
Fellow of the Institute of Molecular Biology
Ph.D., Stanford University, 1966

Program Affiliation: Microbiology

Research Groups Affiliation: Biochemistry | Genetics | Microbiology

Phone: 812/855-3340
Fax: 812/855-6705
Email Milton

Taylor Lab web site

Infection with hepatitis Hepatitis   C virus (HCV) or 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 atitis C is treatment with interferon-alpha (IFN), or more recently combination treatment of IFN-á and ribavirin and the anti-viral drug ribavirin. . More recently IFN-alpha a nd Interferon-gamma have been tried in combination. Following treatment with IFN and ribavirin , sustained response (as defined as no virus   6 months after cessation of treatment) occurs in only 14-20 40-50 % of patients with combination therapy the response is higher, with sustained response being seen in 21% of non-responders and 39% in relapsers from previous treatment with IFN alone . 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 and initial levels of HCV. There have also been marked racial differences in response to IFN. Thus genetic factors (availability of IFN receptors, differential induction of IFN-induced genes, cytokine production?) might be are involved in this response.

In order to investigate this we have run hundred's of DNA microarrays from non-responding and responding patients at different time points. Recent evidence indicates that in approximately 50% of the patients, there is an initial decrease in viral load. This decrease follows biphasic kinetics, suggesting multiple mechanisms of virus inhibition although this may reflect primary inhibition by IFN, and smaller bursts of infected virus from infected cells at a later time. We have initiated a program of attempting to define these characters that may be involved in this variable response, and also at the same time we are examining possible reasons why hepatitis C gives rise to a chronic infection although the immune system appears to be intact. This includes measurement of cytokines, establishing T-cells in culture and an examination of in vivo gene induction by interferon.

A new project is to look at viral titers during early stages of treatment and to identify key genes involved in the decrease in viral titers using bioinformatics techniques.

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 . Changes in gene expression during peginterferon and ribavirin therapy of chronic hepatitis C distinguish responders from non responders to antiviral therapy. J. Virology. 2007,81(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 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. 2007

L. I. Brodsky, A.S.Wahed, J Li, , J . E. Tavis T. Tsukahara and M. W. Taylor. A Novel Unsupervised Method to Identify Genes Important in the anti-viral Response: application to Interferon/Ribavirin in Hepatitis C Patients PLoS ONE, 2007 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.. Differential gene induction by type I and type II interferons and their combination. J. Interferon Cytokine Research. 26 462-7, 2006.

Tsukahara T., Kim S., Taylor M.W. 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, 2006.

Liu, Y., Taylor M.W. Edenberg H.J. Model-based identification of cis-acting elements from Microarray Data., Genomics. May 20, 2006. ( Epub)

Tan, H., Derrick J., Hong J., Sanda C., Grosse W.M., Edenberg H.J. Taylor M.W. Seiwart S., Blatt L.M. 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, 2005.