Our Science

Paul M. Lieberman, Ph.D.

Paul M. Lieberman, Ph.D.

  • Hilary Koprowski, M.D., Endowed Professor
  • Professor and Program Leader, 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 studies how certain viruses establish a long-term latent infection that can lead 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 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.  New research also focuses on the epigenetic controls of latent viruses and human telomeres, and how interactions between viruses and telomeres may induce a malignant transformation of the infected cell.

Selected Publications

1.   Deng Z, Glousker G, et al., Lieberman PM, Tzfati, Y. Inherited mutations in the helicase RTEL1 cause telomere dysfunction and Hoyeraal-Hreidarsson syndrome.  PNAS  2013.  

2.   Dheekollu J, Chen HS, Kaye KM, Lieberman PM. Timeless-dependent DNA replication-coupled recombination promotes Kaposi’s Sarcoma-associated herpesvirus episome maintenance and terminal repeat stability.  J. Virology. 2013 Apr 87(7):369, PMID: 23325691.

3.   Deng Z, Wang Z, Stong N, Plasschaert R, et al. Riethman H, and Lieberman PM. A role for CTCF and cohesion in subtelomere chromatin organization, TERRA transcription, and telomere end protection.  EMBO J. 2012 Nov 31(21):4165, PMID: 23010778.

4.  Kang H, Cho H, Sung GH, Lieberman PM. CTCF regulates Kaposi’s sarcoma-associated herpesvirus latency transcription by nucleosome displacement and RNA polymerase programming. Journal of Virology 2013 Feb 87(3)1789, PMID: 23192870.

5.  Arvey A, Tempera I, Tsai K, Chen HS, Tikhmyanova N, Klichinsky M, Leslie C, Lieberman PM. An atlas of the Epstein-Barr virus transcriptome and epigenome reveals host-virus regulatory interactions. Cell Host Microbe 2012 Aug 12(2)233, PMID: 22901543.

6.  Chen HS, Wikramasinghe P, Showe L, Lieberman PM. Cohesins repress Kaposi’s sarcoma-associated herpesvirus immediate early gene transcription during latency.  Journal Virology 2012 Sep 86(17)9454, PMID: 22740398.

7.  Tsai K, Thikmyanova N, Wojcechowskyj JA, Delecluse HJ, Lieberman PM. EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription.  PLoS Pathogens 2011 Nov 7(11):e1002376, PMID: 22102817.

8.  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., PMID: 20930215

9.  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], PMID: 20929547

10. 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.], PMID: 20855943

11. 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, PMID: 20730088