Yujun Zhang, Ph.D.

Faculty and Fellows

Yujun Zhang, Ph.D.
Assistant Professor of Medicine

 

Undergraduate Education: Department of Biochemistry, Sichuan University, Sichuan, China. B.S., 1982.
Graduate Schools: Department of Biochemistry, Sichuan University, Sichuan, China. M.S., 1984.
Graduate School PhD Program: Department of Biology, University of Massachusetts, Amherst, MA. Ph.D., 1991.
Post-doctoral Fellowship: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA

Special Research Interests:

  • Molecular mechanisms of T cell malignancy and normal T cell biology
  • Signaling and molecular targets during T cell activation

T cell malignancy is a complex process involving activation of proto-oncogenes and inactivation of tumor suppressor genes. We have identified a T-cell specific protein p80, the precursor of Interleukin-16 (IL-16), as a putative tumor suppressor protein for T-cell malignancy. P80 is a PDZ domain-containing nuclear protein highly expressed in quiescent T cells but rapidly diminished upon T cell activation. Genomic deletion or mutations of the p80 gene is a common feature in human T cell malignant cell lines. We demonstrate that p80 inhibits Skp2 expression leading to accumulation of p27KIP1.

On-going research projects in our laboratory include:
(1) elucidating the mechanism(s) by which p80 regulates Skp2 expression; (2) identifying the molecular targets of p80 during T cell malignancy; and (3) examining the signaling in regulation of p80 expression and function during T cell activation. These studies will provide new insights into abnormal T cell proliferation and help to identify diagnostic and/or therapeutic targets for human T cell malignancies.

Selected Publications:

  1. Zhang, Y. , Tuzova, M., Xiao, Z.X., Cruikshank, W.W., and Center, D.M.. (2008) . Pro-Interleukin-16 recruits Histone Deacetylase 3 to the Skp2 Core Promoter through Interaction with Transcription Factor GABP J. Immunol. 180:402-408.
  2. Chang, D.L., Qiu, W., Ying, H., Zhang, Y. , Chen, C.Y., and Xiao, Z.X.. (2007) . ARF Promotes Accumulation of Retinoblastoma Protein through Inhibition of MDM2. Oncogene 26:4627-4634.
  3. Center, D.M., Cruikshank, W.W., Zhang, Y. . ( 2004 ). Nuclear Pro-IL-16 Regulation of T cell Proliferation: p27KIP1-Dependent G0/G1 Arrest Mediated by Inhibition of Skp2 Transcription. J. Immunol. 172: 1654-1660 .
  4. Wilson , K.C., Cruikshank, W.W., Center, D.M., and Zhang, Y. . ( 2003 ). HTLV-1 Tax Oncoprotein Binds to the Precursor of Interleukin-16: a PDZ-Containing Protein. Virology 306: 60-67.
  5. Wilson , K.C., Cruikshank, W.W., Center, D.M., and Zhang, Y. . ( 2002 ). The N-terminal Domain of Prointerleukin-16 Contains a Functional CcN Motif. Biochemistry. 41: 14306-14312.
  6. Zhang, Y. , Kornfeld, H., Cruikshank, W.W., Kim, S., Reardon, C.C., and Center, D.M.. ( 2001 ) Nuclear Translocation of the N-terminal Pro-domain of Interleukin-16. J. Biol. Chem. 276: 1299-1303.
  7. Wu, D.M.HJ., Zhang, Y. , Parada, N.A., Kornfeld, H., Nicoll, J., Center, D.M., and Cruikshank, W.W. ( 1999 ) Processing and Release of IL-16 from CD4+ But Not CD8+ T Cells Is Activation Dependent. J. Immunol. 162: 1287-1293.
  8. Keane, J., Nicoll, J., Kim, S., Wu, D.M.H. Cruikshank, W.W., Brazer, W., Natke, B., Zhang, Y. , Center, D.M., and Kornfeld, H. ( 1998 ) Conservation of Structure and Function Between Human and Murine IL-16. J. Immunol. 160: 5945-5954.
  9. Zhang, Y. , Center, D.M., Wu, D.M.H., Cruikshank, W.W., Yuang, J., Andrews, D.W. and Kornfeld, H. ( 1998 ) Processing and Activation of pro-IL-16 by caspase 3. J Biol Chem. 273: 1144-1149.
  10. Yen, H., Zhang, Y. , Penfold, S., and Rollins, B.J. ( 1997 ) MCP-1 mediated chemotaxis requires activation of non-overlapping signal transduction pathways. J. Leukocyte Biol. 61: 529-532.
  11. Schecter, A.D., Rollins, B.J., Zhang, Y. , Charo, I.F., Fallon, J.T., Rossikhina, M. Giesen, P.L.A., Nemerson, Y., and Taubman, M.B. ( 1997 ) Tissue factor is induced by monocyte chemoattractant protein 1 in human aortic smooth muscle and THP-1 cells. J. Biol. Chem. 272: 28568-28573.
  12. Zhang, Y. , Ernst , C.A. , Rollins, B.J. ( 1996 ) Structure/Activity Analysis. Methods 10: 93-103.
  13. Zhang, Y. , and Rollins, B.J. ( 1995 ) A dominant negative inhibitor indicates that monocyte chemoattractant protein-1 functions as a dimer. Mol. Cell Biol. 15: 4851-4855.
  14. Zhang, Y. , Rutledge, B.J. and Rollins, B.J. ( 1994 ) Structure/activity analysis of human monocyte chemoattractant protein-1 (MCP-1): identification of a mutated protein that inhibits MCP-1 mediated monocyte chemotaxis. J Biol Chem. 269: 15918-5924.
  15. Ernst , C.A. , Zhang, Y. , Hancock, P.R., Rutledge, B.J., Corless, C.L. and Rollins, B.J. ( 1994 ) Biochemical and biological characterization of murine MCP-1: identification of two functional domains. J. Immunol. 152: 2541-2549.

Link:
Immuology/Asthma Research Group

  

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Primary teaching affiliate
of BU School of Medicine