The Milton Taylor Lab

The Taylor lab is using DNA microarrays and bioinformatics technologies to develop better treatments for Hepatitis C (HCV) in concert with the Virahep-C project. This project is funded by the NIDDK with the purpose of studying the differential response of African and Caucasian Americans to interferon-alpha (IFN-a) treatment. Hepatitis C, the leading cause of chronic liver disease worldwide, often leads to cirrhosis of the liver and can cause hepatic cancer.

The only known treatment for HepC is treatment with interferon-alpha (IFN-a), or more recently combination treatment of Pegylated IFN-a and Ribavirin. Only 14-20% of patients achieve a 'sustained response' (a significant reduction in disease burden continuing after cessation of treatment) with IFN-a alone, and combination therapy combination treatment of Pegylated IFN-a and Ribavirin improves to 40-50% sustained responders; other patients either show no response or relapse after the end of treatment.

The biological mechanism behind the dramatically differing responses of patients to IFN is not well understood. Several factors affect the response, including race, age, viral genotype and initial Ievels of HCV. The genetic factors may be differences in the availability of IFN receptors, or differential induction of IFN-induced genes, or differences in cytokine production.

Recent evidence suggests there are many parallel and possibly interacting pathways. The Milton Taylor research lab has initiated a research program to define the unknown factors of this variable response by measuring cytokines levels and examining the relationships between genes that are up-regulated and down-regulated in patients treated with IFN using DNA (Affymetrix) microarrays in collaboration with the Center for Medical Genomics in Indianapolis.

A second project, funded by Intermune, is a study of the synergistic activity of IFNs of different subtypes, both on viral infection and tumour growth. This interaction is being studied using DNA microarrays, proteomics and bioinformatics.

People

MiltonTaylor
Principal Investigator
Mary Ferris
Lab administrator
Joel Schaley
Biol postdoc researcher
Baochang Fan
Biol postdoc researcher
Takuma Tsukahara
Bioinfo research associate

Publications

Taylor MW, Grosse WM, Schaley JE, Sanda C, Wu X, Chien SC, Smith F, Wu TG, Stephens M, Ferris MW, McClintick JN, Jerome RE, Edenberg HJ.
Global effect of PEG-IFN-alpha and ribavirin on gene expression in PBMC in vitro. PUBMED
J Interferon Cytokine Res. 2004 Feb;24(2):107-18
Manuscript
Supplementary Table 1 - upregulated genes
 Supplementary Table 1 - upregulated genes (with name aliases, EXCEL file)
 Supplementary Table 2 - downregulated genes

Sanda C, Weitzel P, Tsukahara T, Schaley J, Edenberg HJ, Stephens MA, McClintick JN, Blatt LM, Li L, Brodsky L, Taylor MW.
Differential gene induction by type I and type II interferons and their combination. PUBMED
J Interferon Cytokine Res. 2006 Jul;26(7):462-72

Tsukahara T, Kim S, Taylor MW.
REFINEMENT: A search framework for the identification of interferon-responsive elements in DNA sequences--a case study with ISRE and GAS PUBMED
Comput Biol Chem. 2006 Apr;30(2):134-47. Epub 2006 Mar 20.
Manuscript
REFINEMENT website



Articles and Links

REFINEMENT website
http://cancer.informatics.indiana.edu/ttsukaha

NIH clinical trial to assess race as factor in treatment success
http://www.homepages.indiana.edu/051002/text/nih.html

Walther Cancer Institute
http://www.walther.org/wcf_users_homepages/Taylor_Milton.html

The effects of interferon on the expression of human papillomavirus oncogenes
http://vir.sgmjournals.org/cgi/content/abstract/81/3/695

Departmental web page
http://www.bio.indiana.edu/facultyresearch/faculty/Taylor.html

National Center for Infectious Diseases - Viral Hepatitis C
http://www.cdc.gov/ncidod/diseases/hepatitis/c/

All About Hepatits C
http://www.all-about-hepatitisc.com/getting_treated/approaches.jsp

National Hepatitis Coalition
http://nationalhepatitis-c.org/

Hepatitis C InfoCenter
http://www.hepnet.com/hepc.html

Medline Hepatitis C
http://www.nlm.nih.gov/medlineplus/hepatitisc.html

10/24/2006