Paul M Lieberman

faculty photo
Wistar Institute Professor of Microbiology
Department: Microbiology

Contact information
The Wistar Institute
Dept of Molecular Genetics, Rm 201
3601 Spruce St
Philadelphia, PA 19104-4265
Office: 215 898-9491
Fax: 215 898-0663
Graduate Group Affiliations
Education:
BA (Chemistry)
Cornell University, 1983.
Ph.D. (Molecular Virology)
The Johns Hopkin's University School of Medicine, 1989.
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Description of Research Expertise

Research Interests
Genome maintenance and gene expression; Gammaherpesviruses and oncogenesis; Telomere Biology, Chromatin structure and genome stability; Transcription regulation.

Key words: viral latency, telomeres, chromatin, DNA replication, transcription regulation, herpesvirus.

Description of Research

Mechanisms of Genome Stability and Control of Viral Latency

The human tumor viruses, EBV and KSHV, establish latent infection in various tissues and serve as cofactors in lymphoid and epithelial cell malignancies. These latent viruses persist as nuclear minichromosomes for multiple generations in proliferating cells. Survival of the viral genome depends on viral-encoded and cellular factors involved in DNA replication, epigenetic organization, and chromosome dynamics. One project in the lab focuses on the role of telomere repeat factors (TRFs) in regulating viral genome stability by preventing a host DNA damage response to viral DNA. Recent studies have revealed that a telomere repeat containing non-coding RNA, termed TERRA, is bound by TRF2 and required for chromosome stability of the virus and the host cell. The role of TERRA in genome stability and response to environmental stresses, including viral infection, are under investigation. A second area of interest involves the organization of the genome into active and inactive regions through the boundary factor CTCF. We have found that CTCF coordinates RNA polymerase II transcription with a pattern of epigenetic markings. The mechanism through which CTCF establishes epigenetic boundaries is important for heritable, stable gene expression and ultimately for genome stability. A third major effort in the lab is to identify small molecule inhibitors of latent viral infection using high-throughput screening, chemo-informatic approaches, and chemical derivatization. Rotation students are welcome to explore various aspects of these research projects.


Rotation Projects for 2006-2007
1. Characterization of non-coding telomere RNA (TERRA) in genome stability
2. Genome stability of gammaherpesviruses, EBV and KSHV
3. Role of CTCF and microRNA in establishing epigenetic code
4. High-Throughput Screening for inhibitors of latent virus infection


Lab personnel:

Zhong Deng, Ph.D., Postdoctoral Fellow
Raju Dheekollu, Ph.D., Postdoctoral Fellow
Fang Lu, Ph.D., Postdoctoral Fellow
Pu Wang, Ph.D., Postdoctoral Fellow
Hyojeung Kang, Ph.D., Postdoctoral Fellow
Julie Norseen, Predoctoral Student (GGR)
Andrew Rennekamp, Predoctoral Student (MVP
Kevin Tsay, Predoctoral Student (MVP)
Andreas Wiedmer, Research Technician
Scott Thompson, Research Technician

Description of Itmat Expertise

Human Tumor Viruses
Latency and Carcinogenesis
Chromatin and Epigenetic Control
Drug Discovery and High-Throughput Screening

Selected Publications

Lu F, Zhou J, A Wiedman, Y Yuan, Lieberman, PM : Chromatin remodeling of KSHV ORF50 promoter correlates with reactivation from latency. J. Virol 2003.

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: 2633-44, 2003.

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. Page: 493-503, 2003.

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: 10334-47, 2001.

Solow, S., Salunek, M., and Lieberman, P. M. : Human TAFII250 phosphorylates TFIIA on serine residues important for TBP binding and transcription activation. J. Biol. Chem. 276: 15886-92, 2001.

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Last updated: 04/03/2013
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