Tim Block

Timothy Block

Professor, Microbiology and Immunology
Director, Drexel Institute for Biotechnology and Virology Research

Ph.D., 1979, SUNY-Buffalo: Roswell Park Memorial Institute, Buffalo, N.Y., Post doctoral (1982): Princeton University.

3805 Old Easton Road
Doylestown, PA 18902

Tel: 215-489-4948
Fax: 215-489-4920
Email: tim.block@drexelmed.edu

Research Staff: working closely with Anand Mehta, D. Phil. (Associate Professor and with the labs of research faculty: JuTau Guo, M.D.; Jinhong Chang, M.D., Ph.D., HaiTau Guo, Ph.D., Ying Su, Ph.D., Andrea Cuconati, Ph.D., Alex Birk, Ph.D., Pamela Norton, Ph.D., Xuanyong Lu, Ph.D., Ramilla Philip, Ph.D).
Graduate Students: Jessica Kennedy, Lorena Loraca

Keywords:

Hepatitis B, Hepatitis C, Viral hepatitis, Herpes simplex, Liver Cancer, Biomarkers, Glycobiology, Glycoproteomics, West Nile Virus, High Throughput Screening

Research Interests

Our lab is studying chronic viral diseases. The molecular mechanisms of herpes simplex virus latency continues to be an important area. However, most of our work is in the area of hepatitis B and C and liver cancer. With a glycobiology research theme, we search for antiviral agents and their mechanism of action (two of our discoveries have led to therapies now in human clinical trials); for biomarkers of disease, using glycoproteomics (two of our discoveries have led to biomarkers being tested in people for the early detection of liver and colorectal disease); and to understand disease by examining the role of protein folding in antigen presentation and how the viruses antagonize and oppose the host innate immune system.

In particular, we are actively investigating and developing a group of broad-spectrum antiviral iminosugar compounds that act upon the cellular glycosidase and, hence, viral glycoprotein processing pathways. In addition to maximizing the potency and minimizing the toxicity of these compounds, we are also further investigating their mechanism of action both in tissue culture and in animal models.

We recently started a high-throughput screening effort using West Nile Virus replicon cells to screen for novel small molecule antivirals inhibiting the viral RNA replication as well as boosting host cell innate immune system. The hits from the screen will be triaged by their activity, specificity, toxicity, mode of action, chemical development and more.

Our lab works in close collaboration with the University of Pennsylvania, University of Oxford, University of Michigan, Fox Chase Cancer Center and other nonprofit research organizations including the Hepatitis B Foundation and its research affiliate, the Institute for Hepatitis and Virus Research.

Selected Research Publications

Block, T. M., Guo, H. and J. T. Guo. Molecular virology of hepatitis B virus for clinicians. Clinics in Liver Disease of North America, 11(4): 685-706, 2007.
Dougherty, A. M., Guo, H., Westby, G., Liu, Y., Guo, J. -T., Mehta, A. S., Norton, P., Gu, B., Block, T. M. and C. Cuconati. A substituted Tetrazolo-Pyrimidine is a specific and novel inhibitor of hepatitis B virus surface antigen secretion. Antimicrobial Agents and Chemotherapy, 51(12): 4427-4437, 2007.
Choudhari, S. R., Khan, M. A., Harris, G., Picker, D., Jacob, G. S., Block, T. M. and K. Shailubhai. Deactivation of Akt and STAT-3 signaling promotes apoptosis, inhibits proliferation and enhances sensitivity of HCC cells to an anti-cancer agent, Atiprimod. Molecular Cancer Therapeutics, 6(1): 112-121, 2007.
Guo, H., Zhou, T., Jiang, D., Cuconati, A., Xiao, G-H., Block, T. M. and J-T. Guo, J. -T. Regulation of hepatitis B virus replication by a phosphoatidylinositol 3-kinase-Akt signal transduction pathway. Journal of Virology, 81(18): 10072-10080, 2007.
Guo, H., Jiang, D., Zhou, T., Cuconati, A., Block, T. M. and J-T. Guo. Characterization of the intracellular deproteinized relaxed circular DNA of hepatitis B virus: An intermediate of covalently closed circular DNA formation. Journal of Virology, 81(22): 12472-12484, 2007.
Guo, J-T., Zhou, T., Guo, H. and T. M. Block. Alpha interferon induced antiviral response noncytolytically reduces replication defective adenovirus DNA in MDBK cells. Antiviral Research, 76(3): 232-240, 2007.
Gu, B., Mason, P., Wang, L., Norton, P. A., Bourne, N., Moriarty, R. M., Mehta, A., Despande, M., Shah, R. and T. M. Block. Antiviral profiles of deoxynorjirimycins with conformationally restricted and oxygen containing side chains against Bovine Viral Diarrhea virus, West Nile virus, Dengue virus and Hepatitis B virus. Antiviral Chemistry & Chemotherapy, 18(1): 49-59, 2007.
Liu, Y., Simsek, E., Norton, P., Sinnathamby, G., Philip, R., Block, T. M. and T. Zhou. The role of the downstream signal sequences in the maturation of the HBV Middle Surface glycoprotein: Development of a novel therapeutic vaccine candidate. Virology, 365(1): 10-19, 2007.
Jiang, D., Guo, H., Xu, C., Chang, J., Gu, B., Wang, L., Block, T. M. and J.-T. Guo. Identification of three interferon-inducible cellular enzymes that inhibit the replication of hepatitis C virus. Journal of Virology, 82(4): 1665-1678, 2008.
Mehta, A. S., Long, R. E., Comunale, M. A., Wang, M., Rodemich, L., Krakover, J., Philip, R., Marrero, J. A., Dwek, R. A. and T. M. Block. Increased levels of galactose-deficient anti-gal IgG in the sera of HCV infected individuals with fibrosis and cirrhosis. Journal of Virology, 82(3): 1259-1270, 2008.
Hann, H. -W., Han, S. -H., Block, T. M., Harris, M., Maa, J. -F., Fisher, R. T. and E. Atillasoy. Symptomatology and health attitudes of chronic hepatitis B patients in the United States. Journal of Viral Hepatitis, in press, 2008.
Cohen, C., Evans, A. A., London, W. T., Block, J., Conti, M. and T. M. Block. Underestimation of chronic hepatitis B in the US. Journal of Viral Hepatitis, in press, 2008.
Norton, P., Comunale, M. A., Krakover, J., Rodemich, L., Pirog, N., D'Amelio, A., Philip, R., Mehta, A. S. and T. M. Block. N-linked glycosylation of the liver cancer biomarker GP73. Journal of Cellular Biochemistry, in press, 2008.
Su, Y-H., Wang, M., Brenner, D. E., Norton, P. A. and T. M. Block. Detection of mutated K-ras DNA in urine, plasma and serum from patients with colorectal carcinoma of adenomatous polyps. Annals of New York Academy of Sciences, in press, 2008.
Su, Y-H., Song, J., Wang, Z., Wang, X-H., Wang, M., Brenner, D. E. and T. M. Block. Removal of high molecular weight DNA by carboxylated magnetic beads enhances the detection of mutated K-ras DNA in urine. Annals of New York Academy of Sciences, in press, 2008.