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Paul M Lieberman, Ph.D.
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Wistar Institute Professor of Microbiology
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Department: Microbiology
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Contact information
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The Wistar Institute
2a Dept of Molecular Genetics, Rm 201
36 3601 Spruce St
Philadelphia, PA 19104-4265
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2a Dept of Molecular Genetics, Rm 201
36 3601 Spruce St
Philadelphia, PA 19104-4265
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Office: 215 898-9491
32 Fax: 215 898-0663
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32 Fax: 215 898-0663
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Email:
lieberman@wistar.org
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lieberman@wistar.org
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Publications
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Education:
21 7 BA 16 (Chemistry) c
2b Cornell University, 1983.
21 a Ph.D. 1f (Molecular Virology) c
49 The Johns Hopkin's University School of Medicine, 1989.
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Permanent link21 7 BA 16 (Chemistry) c
2b Cornell University, 1983.
21 a Ph.D. 1f (Molecular Virology) c
49 The Johns Hopkin's University School of Medicine, 1989.
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a9 Genome maintenance and gene expression; Gammaherpesviruses and oncogenesis; Telomere Biology, Chromatin structure and genome stability; Transcription regulation.
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76 Key words: viral latency, telomeres, chromatin, DNA replication, transcription regulation, herpesvirus.
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26 Description of Research
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43 Mechanisms of Genome Stability and Control of Viral Latency
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631 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.
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20 Rotation Projects
53 1. Characterization of non-coding telomere RNA (TERRA) in genome stability
40 2. Genome stability of gammaherpesviruses, EBV and KSHV
45 3. Role of CTCF and microRNA in establishing epigenetic code
4e 4. High-Throughput Screening for inhibitors of latent virus infection
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1e Lab personnel:
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2e Zhong Deng, Ph.D., Postdoctoral Fellow
32 Raju Dheekollu, Ph.D., Postdoctoral Fellow
2b Fang Lu, Ph.D., Postdoctoral Fellow
2b Pu Wang, Ph.D., Postdoctoral Fellow
31 Hyojeung Kang, Ph.D., Postdoctoral Fellow
30 Julie Norseen, Predoctoral Student (GGR)
32 Andrew Rennekamp, Predoctoral Student (MVP
2d Kevin Tsay, Predoctoral Student (MVP)
2c Andreas Wiedmer, Research Technician
2a Scott Thompson, Research Technician
26 29
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Description of Research Expertise
2b Research Interestsa9 Genome maintenance and gene expression; Gammaherpesviruses and oncogenesis; Telomere Biology, Chromatin structure and genome stability; Transcription regulation.
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76 Key words: viral latency, telomeres, chromatin, DNA replication, transcription regulation, herpesvirus.
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26 Description of Research
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43 Mechanisms of Genome Stability and Control of Viral Latency
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631 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.
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20 Rotation Projects
53 1. Characterization of non-coding telomere RNA (TERRA) in genome stability
40 2. Genome stability of gammaherpesviruses, EBV and KSHV
45 3. Role of CTCF and microRNA in establishing epigenetic code
4e 4. High-Throughput Screening for inhibitors of latent virus infection
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1e Lab personnel:
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2e Zhong Deng, Ph.D., Postdoctoral Fellow
32 Raju Dheekollu, Ph.D., Postdoctoral Fellow
2b Fang Lu, Ph.D., Postdoctoral Fellow
2b Pu Wang, Ph.D., Postdoctoral Fellow
31 Hyojeung Kang, Ph.D., Postdoctoral Fellow
30 Julie Norseen, Predoctoral Student (GGR)
32 Andrew Rennekamp, Predoctoral Student (MVP
2d Kevin Tsay, Predoctoral Student (MVP)
2c Andreas Wiedmer, Research Technician
2a Scott Thompson, Research Technician
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13c 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(21): 10334-47, November 2001.
10a 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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Selected Publications
121 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. 9(3): 493-503, 2003.13c 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(21): 10334-47, November 2001.
10a 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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