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Member Information
Paul Lieberman, PhD
Associate Professor, Gene Expression and Regulation Program
The Wistar Institute
Office Phone:
Office Fax:
Email: lieberman@wistar.org
Website(s): http://www.wistar.org/research_facilities/lieberman/research.htm
Education:
Keywords: Gammaherpesvirus, Gene Expression, Latency, Replication, Genome Stability, Chromatin Organization
Research and/or Clinical Interests:
The regulation of gene expression during gammaherpesvirus latency and reactivation is the primary focus of the lab. This interest also includes a detailed understanding of the chromosome structure of the latent viral genome, including the mechanism of plasmid maintenance and replication during latent infection of proliferating lymphocytes.
Summary:
The gammaherpesviruses, EBV and KSHV, are associated with human malignancies seen most often in immunosuppressed individuals, particularly in the context of HIV- associated AIDS. The Lieberman lab's primary focus is on the viral and cellular mechanisms regulating the establishment, maintenance, and reactivation of gammaherpesvirus latency. They have been exploring the importance of chromatin organization and histone modifications in the regulation of EBV and HHV8/KSHV latency. They have found that nucleosomes may be positioned by Origin Recognition Complex (ORC) proteins that are recruited to the viral genomes by the viral nuclear antigens, EBNA1 for EBV and LANA for KSHV. The Lieberman lab is interested in the relationship between the DNA replication origin used during latency and the establishment of a chromatin-associated genome essential for stable latent infection. They have also found that the immediate early promoters of both gammaherpsviruses are associated with strongly positioned nucleosomes that are maintained in the deacetylated state. Future work will focus on how changes in nucleosome modification and remodeling can regulate transcription programs that control latency and reactivation.
Representative Publications:
Bell, P., Lieberman, P. M., and Maul, G. G. Lytic but not latent replication of Epstein-Barr virus is associated with PML and induces sequential release of nuclear domain 10 proteins. J Virol. 74, 11800-10. 2001.
Chen, C. J., Deng, Z., Kim, A., Blobel, G. A., and Lieberman, P. M. Stimulation of CREB binding protein nucleosomal histone acetyltransferase activity by a class of transcriptional activators. Mol Cell. Biol. 21, 476-487. 2001.
Solow, S., Salunek, M., and Lieberman, P. M. Human TAF II 250 phosphorylates TFIIA on serine residues important for TBP binding and transcription activation. J. Biol. Chem. 276, 15886-15892. 2001.
Deng, Z., Chen, C.-J., Zerby, D., Delecluse, H.-J., and Lieberman, P. M. Identification of acidic and aromatic residues in the Zta activation domain essential for Epstein-Barr virus reactivation. J. Virology 75, 10334-10347. 2001.
Deng, .Z., Lezina, L., Chen, C.-J., Shtivelband, S., So, W., and Lieberman, P. M. Telomeric proteins regulate episomal maintenance of Epstein-Barr Virus Origin of plasmid replication. Mol. Cell., 493-503, 2002.
Deng, Z., Chen, C.-J., Chamberlin, M., Lu, F., Blobel, G. A., Speicher, D., Cirillo, L. A, Zaret, K. S., and Lieberman, P. M. The CBP Bromo domain and nucleosome targeting are required for Zta stimulated histone acetyltransferase activity. Mol. Cell. Biol. 23:2633-2644. 2003.
Lu, F. , Zhou, J., A. Wiedman, Y. Yuan, and Lieberman, P. M. Chromatin remodeling of KSHV ORF50 promoter correlates with reactivation from latency (in press, J. Virology).
Lavens, S., Jacob, M., Leta, M., Lu, F., Lieberman, P. and Pure, E. Identification of protein tyrosine kinases required for B cell receptor-mediated activation of an Epstein-Bar virus immediated early gene promoter. (in press, J. Virology).
Deng, Z., Berg, J., and Lieberman, P. M. Telomere repeat binding factors TRF1, TRF2, and hRap1 modulate replication of Epstein-Barr virus OriP. (in press, J. Virology).
