Office 117
PA Biotechnology Center
3805 Old Easton Road
Doylestown, PA 18902
TEL: 215-489-4948
FAX: 215-489-4920
Timothy.Block@drexelmed.edu
Ph.D. 1979, SUNY-Buffalo, Roswell Park Mem. Inst., NY
Post Doc 1982, Princeton University, Princeton, NJ
Keywords:
Hepatitis B, Hepatitis C, Viral hepatitis, Herpes simplex, Liver Cancer, Biomarkers, Glycobiology, Glycoproteomics, West Nile Virus, High Throughput Screening
Research Interest:
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 peer-reviewed publications (in chronological order)
- Mehta, A.S.; Gu, B.; Conyers, B.; Ouzounov, S.; Wang, L.; Moriarty, R.M.; Dwek, R.A. and Block, T.M. (2004). ?-Galactosylceramide and novel synthetic glycolipids directly induce the innate host defense pathway and have direct activity against hepatitis B and C viruses. Antimicrobial Agents and Chemotherapy, Vol 48 (6), p.2085-90.
- Norton, P.A.; Conyers, B.; Gong, Q.; Steel, L.F.; Block, T.M. and Mehta. A.S. (2005). Assays for glucosidase inhibitors with antiviral activities: using secreted alkaline phosphatase as a surrogate marker. J. Virol. Methods, 124, 167-172
- Block, T.M.; Comunale, M.A.; Lowman, M.; Steel, L.F.; Romano, P.R.; Fimmel, C.; Tennant, B.C.; London, W.T.; Evans, A.A.; Blumberg, B.S.; Dwek, R.A.; Mattu,T. and Mehta., A.S. (2005). Use of targeted glycoproteomics to identify serum glycoproteins that correlate with liver cancer in woodchucks and people. Proc. Nat’l Acad. Science, vol. 102(3), p.779-784.
- Marrero, J.A., P.R., Steel, L.F., Fimmel, C..J., Comunale, M.A., Di Bisceglie A., Lok, Anna S., Block, T.M. (2005). GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma. Hepatology, 43: 1007-1012.
- Schwegler, E.E.; Cazares, L.; Steel, L.F.; Adam, B-L.; Johnson, D.A.; Semmes, O.J.; Block, T.M.; Marrero, J.A. and Drake, R.R. (2005). SELDI-TOF MS profiling of serum for detection of the progression of chronic hepatitis C to hepatocellular carcinoma. Hepatology, Vol 41(3), p.634-642.
- Simsek, E.; Mehta, A.; Zhou, T.; Dwek, R.; Block, T.M. (2005). HBV large and middle glycoproteins appear to be degraded by a proteasome pathway in glucosidase inhibited cells but not in cells with functional glucosidase enzyme. J. Virology 79: 12914-12920.
- Chapman, T. M., Davies, I.G., Gu, B., Block, T.M., Scopes, David, I.C., P.A., Hay, P.A., Courtney, S.M., McNeill, L.A., Schofield, C.J. and Davis, B.G. (2005) Glyco- and peptido-mimetic inhibitors using a three-Component Joullié-Ugi reaction. J Am Chem Soc. 127(2):506-7.
- Comunale, M.A.; Lowman, M; Long, R.E.; Krakover, J., Philip, R.; Seeholzer, S.; Evans, A.A.; Hann, H-W L.; Block, T.M.; Mehta, A.S. (2006). Proteomic analysis of serum associated fucosylated glycoprotein in the development of primary hepatocellular carcinoma. J of Proteome Research 5: 308-315
- Su, Y-H., Wang, M., Aiamkitsumrit, B., Brenner, D.E., and Block, T.M. (2005). Detection of a K-ras mutation in urine of patients with colorectal cancer. Cancer Biomarkers, 1 (2005) 177-182
- Block, T.M.; Mehta, A.S.; Blumberg, B.S.; Dwek, R.A. (2006). Does rapid oligomerization of hepatitis B envelope proteins play a role in resistance to proteasome degradation and enhance chronicity? DNA & Cell Biology. 25 (3): 165-170.
- Zhou, T., Guo, H., Guo, J.T., Cuconati, A., Mehta, A.S. and Block, T.M. (2006). Closed circular (ccc) DNA in HepAD38 cell cultures and may serve as a cccDNA surrogate in antiviral screening assays Antiviral Research (in press)
- Gu, B., Ouzunov, S., Wang, L., Mason, P., Bourne, N., Cuconati, A. and Block, T.M. (2006). Discovery of small molecule inhibitors of West Nile virus using a high-throughput sub-genomic replicon screen. Antiviral Research 70, 39-50.
- Drake, R., Schwegler, E., Malik, G., Diaz, J., Block, T.M., Mehta, A.S. and Semmes, O.J. (2006). Lectin capture strategies combined with mass spectrometry for the discovery of serum glycoprotein biomarkers. Proteome (in press)
- Simsek, E., Lu, X., Ouzounov, S., Block, T.M. and Mehta, A.S. (2006). Alpha glucosidase inhibitors have a prolonged anti-viral effect against hepatitis B virus through the sustained Inhibition of the hepatitis B virus large and middle surface envelope proteins. Antiviral Chemistry and Chemotherapy (in press).
- Su, Y-H; Zhang, X.; Aiamkitsumrit, B. ; Tang, Q. ; Maul, G. ; Fraser, N.W. ; Block, T.M. (2006). The Stability of Herpes Simplex Virus Type I Genomes in Infected Vero Cells Undergoing Viral Induced Apoptosis. Journal of NeuroVirology. 12, 375-386.
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