MICaB Graduate Program
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Xianzheng Zhou, M.D., Ph.D.
Department of Pediatrics
Jiangxi Medical College, 1983, M.D.
Karolinska Institute, 1994, Ph.D.
612-625-4193 - office
612-624-4724 - lab
Human cancer immunology and immunotherapy, transplantation
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
- 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
- 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.