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.
Selected publications:
"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
"Inhibitors of endoplasmic reticulum alpha-glucosidases potently suppress hepatitis C virus virion assembly and release"
Qu X, Pan X, Weidner J, Yu W, Alonzi D, Xu X, Butters T, Block T, Guo J-T, and Chang J.
Antimicrobial Agents and Chemotherapy, In press, 2011.
"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, in press, 2011.
"Analysis of GP73 and fucosylated hemopexin in patients with HCC as a function of anti-cancer treatment"
Hann H, Wang M, Hafner J, Long RE, Kim S, Ahn M, Park S, Comunale MA, Block TM, and Mehta A
Cancer Markers, in press, 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, in press, 2011.
"Indoleamine 2,3-dioxygenase mediates the antiviral effect of gamma interferon against hepatitis B virus in human hepatocytes-derived cells"
Mao R, Zhang J, Jiang D, Cai D, Levy JM, Cuconati A, Block TM, Guo J-T, and Guo H
Journal of Virology, 85(2): 1048-1057, 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
"Interferons accelerate the decay of replication-competent nucleocapsids of hepatitis B virus"
Xu C, Guo H, Pan X-B, Mao R, Yu W, Xu X, Wei L, Chang J, Block TM and Guo J-T
Journal of Virology, 84(18): 9332-9340, 2010.
"Interferon-induced cell membrane proteins, IFITM3 and tetherin, inhibit vesicular stomatitis virus infection via distinct mechanisms"
Weidner JM, Jiang D, Pan X-B, Chan, J, Block TM and Guo J-T
Journal of Virology, 84(24): 12646-12657, 2010
"Glucosidase Inhibition Enhances Presentation of De–N–Glycosylated Hepatitis B Virus Epitopes by Major Histocompatibility Complex Class I In Vitro and in Woodchucks"
Norton PA, Menne S, Gomathinayagam S, Betesh L, Cote PJ, Philip R, Mehta AS, Tennant BC, and Block TM
Hepatology, 52(4): 1242-1250, 2010.
"Evidence that herpes simplex virus DNA derived from quiescently infected cells in vitro, and latently infected cells in vivo, is physically damaged"
Millhouse S, Su Y-H, Zhang X, Wang X, Song BP, Zhu L, Oppenheim E, Fraser NW, and Block TM
Journal of Neurovirology, 16(5): 384-398, 2010.
"Hepatitis B and hepatitis C virus replication upregulates serine protease inhibitor Kazal, resulting in cellular resistance to serine protease-dependent apoptosis"
Lamontagne J, Pinkerton M, Block TM, and X Lu
Journal of Virology, 84(2): 907-917, 2010.
"Identification of Five Interferon-induced Cellular Proteins That Inhibit West Nile Virus and Dengue Virus Infection"
Jiang D, Weidner JM, Qing M, Pan XB, Guo H, Xu C, Zhang X, Birk A, Chang J, Shi PY, Block TM, and Guo J-T
Journal of Virology, 84(16): 8332-8341, 2010.
"Production and function of the cytoplasmic deproteinized relaxed circular DNA of hepadnaviruses"
Guo H, Mao R, Block TM, and Guo J-T
Journal of Virology, 84(1): 387-396, 2010.
"Linkage specific fucosylation of alpha-1-antityrpsin in liver cirrhosis and cancer patients: Implications for a biomarker of hepatocellular carcinoma"
Comunale MA, Rodemich-Betesh L, Hafner J, Wang M, Long RE, Norton P, DiBiceglie AM, Block TM, and Mehta A.
PLOS Pathogens, 5(8): e12419, 2010. |