Our Science

Paul M. Lieberman, Ph.D.

Paul M. Lieberman, Ph.D.

  • Professor, Gene Expression and Regulation Program

  • Director, Center for Chemical Biology and Translational Medicine

  • Scientific Director, Protein Expression and Libraries Facility
  • 215-898-9491, Office
Summary

The laboratory of Paul M. Lieberman uses a variety of genetic techniques to study how certain viruses remain in a latent stage in host immune cells, and more importantly what biochemical pathways spark the virus to awaken and replicate, leading to cancer. The viruses studied include Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV).

Lieberman joined The Wistar Institute in 1995 as an assistant professor. He earned his bachelor’s degree in chemistry from Cornell University and a doctorate in pharmacology/virology from The Johns Hopkins University School of Medicine, which was followed by a postdoctoral fellowship at the University of California, Los Angeles.

In 2010, Lieberman became the first director of The Wistar Institute Center for Chemical Biology and Translational Medicine. Using the advanced screening technologies of Wistar’s Molecular Screening Facility, the Center enables scientists to identify and characterize new molecules and compounds that hold the most promise for developing into therapeutic drugs for cancer and other diseases.

Research in the Lieberman laboratory centers on understanding how the cancer-associated viruses persist in a latent state and increase the risk of cancer cell evolution. EBV and KSHV establish latent infections that are associated with several human malignancies, including Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's disease, and post-transplant lymphoproliferative disorder for EBV, and Kaposi’s Sarcoma for KSHV.

Lieberman and his team have recently found that viral DNA replication and maintenance is regulated by interactions with cellular proteins that bind to telomeres—the repetitive DNA sequences found at the ends of chromosomes. Telomeres protect chromosomes from loss of genetic information, and a similar process is thought to preserve the virus during latency. The Lieberman laboratory has worked out several biochemical pathways that control the stability, replication, and gene expression patterns of the latent virus.

Selected Publications

1 - Dheekollu J, Lieberman PM., The Replisome Pausing Factor Timeless is required for episomal maintenance of latent Epstein-Barr Virus., Journal of Virology. 2011 Apr 13. [Epub ahead of print], 21490103

2 - Rennekamp AJ, Lieberman PM., Initiation of EBV lytic replication requires transcription and the formation of a stable RNA-DNA hybrid molecule at OriLyt., Journal of Virology. 2011 Mar;85(6):2837-50. [Epub 2010 Dec 29], 21191028

3 - Thompson S, Messick T, Schultz DC, Reichman M, Lieberman PM., Development of a high-throughput screen for inhibitors of Epstein-Barr virus EBNA1., Journal of biomolecular Screening. 2010 Oct;15(9):1107-15., 20930215

4 - Lu F, Wikramasinghe P, Norseen J, Tsai K, Wang P, Showe L, Davuluri RV, Lieberman PM., Genome-wide analysis of host-chromosome binding sites for Epstein-Barr virus Nuclear Antigen 1 (EBNA1)., Virology J. 2010 Oct 7;7(1):262. [Epub ahead of print], 20929547

5 - Arthur LM, Demarest RM, Clark L, gourevitch D, et al., Capobianco AJ, Lieberman P, Feigenbaum L, Heber-Katz E., Epimorphic regeneration in mice is p53-dependent., Cell Cycle. 2010 Sep;9(18):3667-73. [Epub 2010 Sep 21.], 20855943

6 - Tempera I, Wiedmer A, Dheekollu J, Lieberman PM., CTCF Prevents the epigenetic drift of EBV Latency Promoter Qp., PLos Pathogens. 2010 Aug 12;6(8). pii:e1001048, 20730088

7 - Iizasa H, Wulff BE, Alla NR, Maragkakis M, Megraw M, Hatzigeorgiou A, Iwakiri D, Takada K, Wiedmer A, Showe L, Lieberman P, Nishikura K., Editing of Epstein-Barr-virus-encoded BART6 microRNAs controls their dicer targeting and consequently affects viral latency., Journal of Biological Chemistry. 2010 Oct 22;285(43):33358-70. [Epub 2010 Aug 17], 20716523

8 - Hou Z, Peng H, White DE, Wang P, Lieberman PM, Halazonetis T, Rauscher FJ 3rd., 14-3-3 binding sites in the snail protein are essential for snail-mediated transcriptional repression and epithelial-mesenchymal differentiation. , Cancer Research. 2010 Jun 1;70(11):4385-93. [Epub 2010 May 25] Erratum in: Cancer Res. 2010 Sep 1;70(17):7012-3., 20501852

9 - Rennekamp AJ, Wang P, Lieberman PM., Evidence for DNA hairpin recognition by Zta at the EBV origin of lytic replication., Journal of Virology. 2010 Jul;84(14):7073-82. [Epub 2010 May 5] , 20444899

10 - Li N, Thompson S, Schultz DC, Zhu W, Jiang H, Luo C, Lieberman PM., Discovery of selective inhibitors against EBNA1 via high throughput in silico virtual screening., PLoS One. 2010 Apr 12;5(4):e10126., 20405039