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:

• 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. 2010 21(1):75-86.
• Huang X, Guo H, Tammana S, Jung YC, Mellgren E, Bassi P, Cao Q, Tu ZJ, Kim YC, Ekker SC, Wu X, Wang SM, Zhou X. Gene Transfer Efficiency and Genome-Wide Integration Profiling of Sleeping Beauty, Tol2, and PiggyBac Transposons in Human Primary T Cells. Mol Ther. 2010 18(10):1803-13.
• Huang X, Haley K, Wong M, Guo H, Lu C, Wilber A, Zhou X.. Unexpectedly high copy number of random integration but low frequency of persistent expression of the sleeping beauty transposase after trans delivery in primary human T cells. Hum Gene Ther. 2010 Nov;21(11):1577-90.
• Chen S, Bohrer LR, Rai AN, Pan Y, Gan L, Zhou X, Bagchi A, Simon JA, Huang H. Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2. Nat Cell Biol. 2010 Nov;12(11):1108-14.
• Lu C, Huang X, Zhang X, Roensch K, Cao Q, Nakayama KI, Blazar BR, Zeng Y, Zhou X.. MiR-221 and miR-155 regulate human dendritic cell development, apoptosis and IL-12 production through targeting of p27kip1, KPC1 and SOCS-1. Blood. 2011 117(16):4293-303.
• Flynn RP, Zacharias J, Zhou X, Cannon ML, Philpott NJ. Non-integrating lentiviral vectors for specific killing of Epstein-Barr virus nuclear antigen 1-positive B cell lymphoma cells. J Gene Med. 2011, 13(9):487-96.