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Zhiyuan Shen, M.D., Ph.D.Shen

Professor and Chief

Division of Radiation Cancer Biology

Tel: 732-235-6101


  • M.D., Norman Bethune University of Medical Sciences, Jilin, China .
  • MS, Institute of Radiation Medicine, Beijing, China
  • Ph.D., Colorado State University, Fort Collins, CO, USA

Academic Appointments:

  • Professor of Radiation Oncology
  • Professor of Pharmacology

Teaching Interests:

Research Interests:

DNA repair, homologous recombination, Cell cycle checkpoint, Maintenance of genomic stability, Modulation of cellular sensitivity to therapeutic DNA damage

Maintenance of genomic stability and prevention of tumorigenesis by precisely regulated homologous recombination (HR) - Genomic instability is a major driving force for tumorigenesis. Mammalian cells use several mechanisms to maintain their genomic stability, including high fidelity DNA replication in S-phase, accurate chromosome segregation in M-phase, precise and error-free repair of DNA damage throughout the cell cycle, and precise cell cycle coordination. HR often precisely repairs DNA double strand breaks, and restarts stalled replication forks to ensure the fidelity of DNA replication and to enable accurate chromosome segregation in mitosis. Thus mis-regulation of HR is a major source of genomic instability. At least four types of HR mis-regulation may occur:

  • HR often uses a sister-chromatid (or a highly homologous region) as the template for DNA repair, and is historically considered an error-free DNA repair pathway. When HR is inhibited, cells may use alternative repair pathways that are more error-prone. Thus, reduced HR is considered a risk factor for tumorigenesis.
  • Mis-resolution of HR DNA intermediates may increase product errors, leading to genomic instability.
  • On the other hand, non-restricted HR may enable recombination between similar sequences, such as repeat sequences of the human genome. This increases the risk of regional chromosome rearrangements, which is a form of genomic instability.
  • HR is highly coordinated with other cellular processes, such as DNA replication, mitosis, and cell cycle regulation. Mis-coordination of HR with cell cycle is expected to be a major source of HR-related genomic instability.

We are interested in how HR is regulated, and coordinated with other cellular processes such as cell cycle regulation and mitosis. We address this issue by examining the functions of proteins that may regulate both HR and cell cycle control. One such protein is BCCIP (BRCA2 and CDKN1A Interacting Protein). Our works have shown that BCCIP regulates HR, cell cycle, and mitosis. Alterations of BCCIP have been implicated in many forms of human cancer. Currently, biochemical, cell and molecular biology, and transgenic approaches are being used to further characterize BCCIP functions and biochemical activities, and its roles in tumorigenesis.

Modulation of cell response to therapeutic DNA damage - Upon DNA damage, three potential outcomes are expected: cell death, survival with full recovery of damaged DNA, or survival with alternations in the genome. The ultimate goal for DNA damage based cancer therapy is to maximize cancer cell death, minimize death of normal cells, and minimize survival with genomic alterations for cancer and normal cells. These outcomes are dictated by two major factors: 1) the initial level of DNA damage received by each cell types; and 2) an intrinsic network of DNA damage response within the cells. This network of DNA damage response includes signal transduction, gene expression regulation, DNA repair, cell cycle checkpoints, and regulation of cell death pathway. After a comprehensive understanding on the mechanism of action for this network, it is possible to modulate this network to favor cancer cell death, while protecting normal cells. We are interested in developing strategies to modulate the cell responses to DNA damage to increase cancer treatment efficacy while reducing side effects. Cell based screen systems are being developed to identify drug targets and drugs to sensitize cancer to therapeutic DNA damage. We are also interested in identifying markers that may predict clinical outcomes of therapeutic DNA damage.  

Lab personnel:

Currently, there are two research staff, two postdoctoral fellows, two PhD graduate students, and one visiting scientist in Dr. Shen lab

Dr. Shen lab is open to rotation graduate students from the Molecular Bioscience Program, and the Program ,

Selected Peer-Reviewed Publications for the Recent Years:

  1. Wray J, Liu J, Nickoloff JA, and Shen Z. Distinct RAD51 Associations with RAD52 and BCCIP in Response to DNA Damage and Replication Stress. Cancer Research, 2008; 68(8):2699-2707. For a copy of pdf reprint, please visit:
  2. Lu H, Yue J, Meng X, Nickoloff JA, and Shen Z. 2007. BCCIP regulates homologous recombination by distinct domains and suppresses spontaneous DNA damage. Nucleic Acids Res . 2007 (Epub ahead of print Oct 18) 35:7160-7170. For copy of PDF reprint, please visit:
  3. Meng X, Fan J, and Shen Z. 2007. Roles of BCCIP in Chromosome Stability and Cytokinesis. Oncogene, Oncogene . 2007 Sep 20; 26 ( 43 ): 6253-60 . (Epub 2007 Apr 23.)   For copy of PDF reprint, please visit:
  4. Meng X., Yue J., Liu Z., and Shen Z. 2007. Abrogation of the transactivation activity of p53 by BCCIP down-regulation. J. Boil Chem. 282(3): 1570-1576 ( Epub 2006 Nov 29).    For copy of PDF reprint, please visit:
  5. Shen Z, Nickoloff JA. (2007) Mammalian Homologous Recombination Repair and Cancer Intervention. In “DNA Repair, Genetic Instability, and Cancer” Chapter 5, pp119-156. Editors: Wei Q, Li L, and Chen DJ. World Scientific Publishing Co. Pte. Ltd., Singapore.
  6. Lu, H., Guo, X., Meng, X., Liu, J., Allen, C., Nickoloff, J.A., and Shen, Z 2005. The BRCA2-Interacting Protein BCCIP Functions in RAD51 and BRCA2 Focus Formation and Homologous Recombinational Repair. Mol. Cell. Biol. 25(5):1949-1957.  For copy of PDF reprint, please visit:
  7. Meng, X., Lu, H., and Shen, Z . 2004. BCCIP functions through p53 to regulate the expression of p21(Waf1/Cip1). Cell Cycle , 3(11): 1457-1462.
  8. Meng, X., Liu, J., and Shen, Z . 2004. Inhibition of G1 to S Cell Cycle Progression by BCCIP b . Cell Cycle , 3: 343-357.
  9. Meng, X., Yuan, Y., Maestas, A., and Shen, Z . 2004. Recovery from DNA Damage-induced G2 Arrest Requires Actin-binding Protein Filamin-A/Actin-binding Protein 280. J Biol Chem , 279: 6098-6105 (e-publication on Dec-2, 2003).  For copy of PDF reprint, please visit:
  10. Meng, X., Liu, J. & Shen, Z . 2003. Genomic structure of the human BCCIP gene and its expression in cancer. Gene 302, 139-46.
  11. Liu, J., Meng, X, and Shen. Z . 2002. Association of human Rad52 protein with transcription factors. Biochem. Biophys. Res. Commun . 297(5): 1191-1196.
  12. Mo, Y., Yu, Y., Shen, Z ., and Beck W.T., 2002. Nucleolar delocalization of human topoisomerase I in response to topotecan correlates with sumoylation of the protein. J. Biol. Chem. 277: 2958-2964.
  13. Yuan, Y., and Shen, Z. 2001. Interaction with BRCA2 suggests a role of filamin-A (hsFLNa) in DNA damage response. J. Biol. Chem. 276: 48318-48324.                                                                                                              For copy of PDF reprint, please visit:
  14. Kim, P.M., Allen, C.P., Wagener, B.M., Shen, Z ., and Nickoloff, J.A. 2001. Overexpression of RAD51 and RAD52 reduces double-strand break-induced homologous recombination in mammalian cells. Nucleic Acids Res . 29(21): 4352-60.
  15. Liu, J., Yuan, Y., Huan, J., and Shen, Z. 2001. Inhibition of brain and breast cancer cell growth by BCCIP a , an evolutionarily conserved nuclear protein that interacts with BRCA2. Oncogene , 20:336-345.                               For copy of PDF reprint, please visit: