Xianzheng Zhou, M.D., Ph.D. Assistant Professor Department of Pediatrics Jiangxi Medical College, 1983, M.D. Karolinska Institute, 1994, Ph.D. zhoux058@umn.edu 612-625-4193 - office 612-624-4724 - lab

Research Interests:

Human cancer immunology and immunotherapy, transplantation immunology

Allogeneic hematopoietic stem cell transplantation represents the most powerful approach to cure human hematological malignancies through the graft-versus-tumor (GVT) effect, although it is often associated with a complication of graft-versus-host disease (GVHD). The long-term goal of my research is to identify molecular targets recognized by donor T cells for segregating GVT from GVHD using cellular immunology and molecular biology approaches. Currently there are two major research themes in my laboratory. One theme is to investigate adoptive donor T cell therapy for leukemia and lymphoma. Under this aim, we are testing if the Sleeping Beauty (SB) transposon system, a mobile DNA, can mediate long-term therapeutic gene expression in human primary T cells for the treatment of refractory leukemia. The other theme is to identify and characterize GVT and GVHD associated antigens including leukemia stem cell antigens and minor histocompatibility antigens. With this information, we will be able to track antigen-specific T cells in transplant patients and develop strategies to augment GVT and prevent GVHD.

.Selected Recent Publications:

• Zhou, X., Berglund, P., Zhao, H., Liljeström, P., and Jondal, M. Generation of cytotoxic and humoral immune responses by nonreplicative recombinant Semliki Forest virus. Proc. Natl. Acad. Sci. USA. 1995. 92:3009-3013.

• Suzue, K., Zhou, X, Eisen, H. N., and Young, R. Heat shock proteins as vehicles for antigen delivery into the class I presentation pathway. Proc. Natl. Acad, Sci. USA. 1997. 94: 13146-13151.
  

• Zhou, X., Wong, S., Walter J., Jacks, T., and Eisen, H. N. Increased generation of CD8+ T cell clones in p53 mutant mice. J. Immunol. 1999. 162:3957-3960.

• Walter J.B., Garboczi, D.N., Fan, Q.R., Zhou, X., Walker, B.D., and Eisen, H.N. A mutant human beta2-microglobulin can be used to generate diverse multimeric class I peptide complexes as specific probes for T cell receptors. J. Immunol. Methods. 1998. 214 (1-2):41-50.
  

• Lu, Z., Yuan, L., Zhou, X., Levitsky, H.L., and Pardoll, D.M. CD40-independent pathways of T cell help for priming of CD8+ cytotoxic T lymphocytes. J. Exp. Med. 2000. 191:541-550.

• Zhou, X., Cui, Y., Huang, X., Yu, Z., Thomas, A.M., Pardoll, D.M., Jaffee, E.M., and Cheng L. Lentiviral-mediated gene transfer and expression in established human tumor antigen-specific cytotoxic T cells and primary unstimulated T cells. Hum. Gene Ther. 2003. 14:1809-1105.
  

• Zhou, X., Jun, D.Y., Huang, X., Huang, L.-Q., Mautner, J., Yu, Z., Thomas, A.M., Mo, W., Robbins, P.F., Pardoll, D.M., and Jaffee, E.M. Diverse CD8+ T cell responses to renal cell carcinoma antigens in patients treated with an autologous GM-CSF gene-transduced renal tumor cell vaccine. Cancer Res. 2005. 65:1079-1088.

• Huang, X., Wilber, A., Bao, L., Dong, T., Tolar, J., Orchard, P., Levine, B.L., June, C.H., McIvor, R.S., Blazar, B.R., and Zhou, X. Stable gene transfer and expression in human primary T cells by the Sleeping Beauty transposon system. Blood. 2006. 107:483-491.
  

• Ravi, R., Fuchs, E.J., Jain, A., Pham, V., Yoshimura, K., Prouser, T., Jalla, S., Zhou, X., Garrett-Mayer, E., Kaufmann, S.H., Schulick, R., Pardoll, D.M., and Bedi, A. Resistance of cancers to immunologic cytotoxicity and adoptive immunotherapy via XIAP expression and co-exisiting defects in mitochondrial death signaling. Cancer Res. 2006. 66:1730-1739.

• Huang X, Guo H, Kang J, Choi S, Zhou TC, Tammana S, Lees CJ, Li ZZ, Milone M, Levine BL, Tolar J, June CH, Scott McIvor R, Wagner JE, Blazar BR, Zhou X.Sleeping Beauty Transposon-mediated Engineering of Human Primary T Cells for Therapy of CD19(+) Lymphoid Malignancies. Mol Ther. 2008 Mar;16(3):580-589.
  
  
• Huang X, Wilber A, McIvor RS, Zhou X. 2009. DNA transposons for modification of human primary T lymphocytes. Methods Mol Biol. 2009;506:115-26.

• Bao L, Guo H, Huang X, Tammana S, Wong M, McIvor RS, Zhou X, 2009. High-titer lentiviral vectors stimulate fetal calf serum-specific human CD4 T-cell responses: implications in human gene therapy. Gene Ther. 16(6):788-95.

• Xue X, Huang X, Nodland SE, Mátés L, Ma L, Izsvák Z, Ivics Z, LeBien TW, McIvor RS, Wagner JE, Zhou X. Stable gene transfer and expression in cord blood-derived CD34+ hematopoietic stem and progenitor cells by a hyperactive Sleeping Beauty transposon system. Blood. 2009 Aug 13;114(7):1319-30.

• Tammana S, Huang X, Wong M, Milone MC, Ma L, Levine BL, June CH, Wagner JE, Blazar B, Zhou X. 4-1BB and CD28 Signaling Plays A Synergistic Role in Redirecting Umbilical Cord Blood T Cells Against B-Cell Malignancies. Hum Gene Ther. 2009. [Epub ahead of print]

Last updated: September 2, 2009