tIMOTHY bLOCVK
Timothy M Block, PhD
President (HBF, BSBI, PA Bio Center) (Principal Investigator) 
Ph: (215) 489-4900
Email:  tim.block@bblumberg.org


TRAINING

(1982) Postdoctoral Fellow Princeton University
(1979) Ph.D State University of New York at Buffalo

Appointment at the Baruch S. Blumberg Institute: President of the Baruch S. Blumberg Institute; Professor and Chair, Department of Translational Research

Other appointments: Adjunct Professor, University of Pennsylvania School of Medicine and Drexel University College of Medicine.  President: Hepatitis B Foundation and Pennsylvania Biotechnology Center

RESEARCH OVERVIEW

Research interest: Molecular mechanisms of viral persistence and development of therapeutic strategies for hepatitis B virus (HBV), filoviruses

Research staff: Working closely with Prof. Tianlun Zhou and Jinhong Chang and other faculty at the Blumberg

RESEARCH

The Baruch S. Blumberg Institute (BSBI) is studying chronic viral diseases. Most of BSBI’s work is in the area of hepatitis B and C and liver cancer. With a glycobiology research theme, the team searches 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.

Dr. Block and the Blumberg faculty are also actively pursuing new therapeutics for the management of hepatitis B, by developing new assays and implementing new screens, using our compound library and natural products collection.

In particular, BSBI is screening for and evaluating new inhibitors of HBV cccDNA as well as HBV sAg.  We are also using combination screening approaches, early in discovery.

BSBI is also 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.

The BSBI labs work in close collaboration with the University of Pennsylvania, University of Oxford, Fox Chase Cancer Center, Drexel University College of Medicine, Johns Hopkins University, Harvard Medical School and other for profit and nonprofit research organizations.

RESEARCH SUMMARY

Molecular mechanisms of viral persistence and development of therapeutic strategies for management of hepatitis B virus (HBV)

RECENT PUBLICATIONS:

Liang, T. Jake, Timothy M. Block, Brian J. McMahon, Marc G. Ghany, Stephan Urban, Ju-Tao Guo, Stephen Locarnini, Fabien Zoulim, Kyong-Mi Chang, and Anna S. Lok. “Present and future therapies of hepatitis B: From discovery to cure.” Hepatology (2015).

Block, Timothy M., Siddhartha Rawat, and Carol L. Brosgart. “Chronic hepatitis B: A wave of new therapies on the horizon.” Antiviral research 121 (2015): 69-81.

Gish, Robert G., Chari A. Cohen, Joan M. Block, Carol L. Brosgart, Timothy M. Block, Ryan Clary, Loc T. Le, Michael H. Ninburg, Lorren Sandt, and Kris V. Kowdley. “Data supporting updating estimates of the prevalence of chronic hepatitis B and C in the United States.” Hepatology (2015).

Yan, Ran, Xuesen Zhao, Dawei Cai, Yuanjie Liu, Timothy M. Block, Ju-Tao Guo, and Haitao Guo. “The Interferon-Inducible Protein Tetherin Inhibits Hepatitis B Virus Virion Secretion.” Journal of virology 89, no. 18 (2015): 9200-9212.

Zhao, Xuesen, Fang Guo, Mary Ann Comunale, Anand Mehta, Mohit Sehgal, Pooja Jain, Andrea Cuconati et al. “Inhibition of Endoplasmic Reticulum-Resident Glucosidases Impairs Severe Acute Respiratory Syndrome Coronavirus and Human Coronavirus NL63 Spike Protein-Mediated Entry by Altering the Glycan Processing of Angiotensin I-Converting Enzyme 2.” Antimicrobial agents and chemotherapy 59, no. 1 (2015): 206-216.

Guo, Fang, Yanxing Han, Xuesen Zhao, Jianghua Wang, Fei Liu, Chunxiao Xu, Lai Wei et al. “STING agonists induce an innate antiviral immune response against hepatitis B virus.” Antimicrobial agents and chemotherapy 59, no. 2 (2015): 1273-1281.

Jain, Surbhi, Lijia Xie, Batbold Boldbaatar, Selena Y. Lin, James P. Hamilton, Stephen J. Meltzer, Shun-Hua Chen et al. “Differential methylation of the promoter and first exon of the RASSF1A gene in hepatocarcinogenesis.” Hepatology Research (2015).

Jain, Surbhi, Ting-Tsung Chang, Sitong Chen, Batbold Boldbaatar, Adam Clemens, Selena Y. Lin, Ran Yan et al. “Comprehensive DNA methylation analysis of hepatitis B virus genome in infected liver tissues.” Scientific reports 5 (2015).

Jain, Surbhi, Ting-Tsung Chang, Sitong Chen, Batbold Boldbaatar, Adam Clemens, Selena Y. Lin, Ran Yan et al. “Comprehensive DNA methylation analysis of hepatitis B virus genome in infected liver tissues.” Scientific reports 5 (2015).

Zhao, X., Guo, F., Liu, F., Cuconati, A., Chang, J., Block, T. M., & Guo, J. T. (2014). Interferon induction of IFITM proteins promotes infection by human coronavirus OC43. Proceedings of the National Academy of Sciences, 111(18), 6756-6761.

Chang, Jinhong, Timothy M. Block, and Ju-Tao Guo. “Viral resistance of MOGS-CDG patients implies a broad-spectrum strategy against acute virus infections.” Antiviral therapy (2014).

Mao, Richeng, Hui Nie, Dawei Cai, Jiming Zhang, Hongyan Liu, Ran Yan, Andrea Cuconati, Timothy M. Block, Ju-Tao Guo, and Haitao Guo. “Inhibition of hepatitis B virus replication by the host zinc finger antiviral protein.” PLoS Pathog 9, no. 7 (2013): e1003494.

Liu, Fei, Matthew Campagna, Yonghe Qi, Xuesen Zhao, Fang Guo, Chunxiao Xu, Sichen Li et al. “Alpha-interferon suppresses hepadnavirus transcription by altering epigenetic modification of cccDNA minichromosomes.” (2013): e1003613.