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 glucosidase 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.
"Design, Synthesis, and Biological Evaluation of N-Alkylated Deoxynojirimycin (DNJ) Derivatives for the Treatment of Dengue Virus Infection"
Yu W, Gill T, Wang L, Du Y, Ye H, Qu X, Guo J-T, Cuconati A, Zhao K, Block TM, Xu X and J Chang
Journal of Medicinal Chemistry, 55(13): 6061-6075, 2012.
"Detection of hypermethylated vimentin in urine of patients with colorectal cancer"
Song BP, Jain S, Lin SY, Chen Q, Block TM, Song W, Brenner DE, Su Y-H
The Journal of Molecular Diagnostics, Volume 14, Issue 2 , Pages 112-119, March 2012
"Quantitative dynamics of hepatitis B basal core promoter and precore mutants before and after HBeAg seroconversion"
Nie H, Evans AA, London WT, Block TM and XD Ren
Journal of Hepatology, 56(4): 795-802, 2012.
"Direct evidence that HSV DNA damaged by Ultra Violet (UV) irradiation can be repaired in a cell type dependent manner"
Millhouse S, Wang X, Fraser NW, Faber L and TM Block
Journal of NeuroVirology, 18(3): 231-243, 2012.
"Increased levels of tetra-antennary N-linked glycans but not core fucolosylation are associated with hepatocellular carcinoma tissue"
Mehta AS, Norton P, Liang H, Comunale MA, Wang M, Rodemich-Betesh L, Koszycki A, Noda K, Miyoshi E and TM Block
Cancer Epidemiology, Biomarkers & Prevention, 21(6): 925-933, 2012.
"Chemically-blocked Antibody Microarray for Multiplexed High-throughput Profiling of Specific Protein Glycosylation in Complex Samples"
Lu C, Wonsidler JL, Li J, Du Y, Block TM, Haab B and S Chen
Journal of Visualized Experiments, (63). pii: 3791, 2012.
"Interleukin-6 and Oncostatin M are elevated in liver disease in conjunction with candidate hepatocellular carcinoma biomarker GP73"
Liang H, Block TM, Wang M, Nefsky B, Long R, Hafner J, Mehta AS, Marrero J, Gish R, PA Norton
Cancer Biomarkers, In press, 2012.
"Impact of the Location of CpG Methylation within the GSTP1 Gene on Its Specificity as a DNA Marker for Hepatocellular Carcinoma"
Jain S, Chen S, Chang KC, Lin YJ, Hu CT, Boldbaatar B, Hamilton JP, Lin SY, Chang TT, Chen SH, Song W, Meltzer SJ, Block TM and Y-H Su
PLoS One, 7(4): e35789, 2012.
"Characterization of the Host Factors Required for Hepadnavirus Covalently Closed Circular (ccc) DNA Formation"
Guo H, Xu C, Zhou T, Block TM and J-T Guo
PLoS One, 7(8): e43270, 2012.
"RO 90-7501 Enhances TLR3 and RLR Agonist Induced Antiviral Response"
Guo F, Mead J, Aliya N, Wang L, Cuconati A, Wei L, Li K, Block TM, Guo J-T and J Chang
PLoS One, 7(10): e42583, 2012.
"Identification of the Disubstituted Sulfonamide Compounds as Specific Inhibitors of Hepatitis B Virus Covalently Closed Circular DNA Formation"
Cai D, Mills C, Yu W, Yan R, Aldrich C, Saputelli J, Mason W, Xu X, Guo J-T, Block TM, Cuconati A and H Guo
Antimicrobial Agents and Chemotherapy, 56(8): 4277-4288, 2012.
"Overexpression of alpha1,6-fucosyltransferase in hepatoma enhances expression of Golgi phosphoprotein 2 in fucosylation-independent manner"
Kawamoto S, Moriwaki K, Nakagawa T, Terao M, Shinzaki S, Yaman-Ohnuki N, Satoh M, Mehta AS, Block TM, and Miyoshi E.
International Journal of Oncology, 39(1): 203-208, 2011.
"Novel changes in glycosylation of serum Apo-J in patients with hepatocellular carcinoma"
Comunale MA, Wang M, Rodemich-Betesh L, Hafner J, Lamontagne A, Klein A, Marrero J, Di Bisceglie A, Gish R, Block TM, and Mehta A
Cancer Epidemiology, Biomarkers & Prevention, 20(6): 1222-1229, 2011.
"Alkylated porphyrins have broad antiviral activity against hepadnaviruses, flaviviruses, filoviruses and arenaviruses"
Guo H, Pan X, Mao R, Zhang X, Wang L, Lu X, Chang J, Guo J-T, Passic S, Krebs FC, Wigdahl B, Warren TK, Retterer CJ, Bavari S, Xu X, Cuconati A and Block TM
Antimicrobial Agents and Chemotherapy, 55(2): 478-486, 2011.
"Combination of alpha-glucosidase inhibitor and ribavirin for the treatment of dengue virus infection in vitro and in vivo"
Chang J, Schul W, Butters TD, Yip A, Liu B, Goh A, Lakshminarayana SB, Alonzi D, Reinkensmeier G, Pan X, Qu X, Weidner JM, Wang L, Yu W, Borune N, Kinch MA, Rayahin JE, Moriarty R, Xu X, Shi PY, Guo J-T, and Block TM
Antiviral Research, 89(1): 26-34, 2011
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