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Wei-ping Zeng, Ph.D.

Research Associate Professor of
Pathology and Laboratory Medicine

Molecular Mechanisms for T cell Activation
and Functional Differentiation

URMC Labs
601 Elmwood Ave., Rm 1-6932
Rochester, NY 14642-8626
Tel: (585) 273-1402
Fax: (585) 756-4133

Weiping_Zheng@urmc.rochester.edu

Dr. Zeng is currently funded by the Crohn's and Colitis Foundation of America for a study of the role of regulatory T cells in inflammatory bowel disease.

Qualifications

Ph.D., State University of New York at Buffalo 1995
Postdoctoral Fellow, Howard Hughes Medical Institute, Yale University School of Medicine 1995-97
Postdoctoral Fellow, Immunobiology, Yale University School of Medicine 1997-99

Research Overview

CD4 T cells play a key role in determining the immune responses that occur in response to exogenous and self antigens, through the production of different sets of cytokines. The cytokines mediate many of the functions of CD4 T cells and the unique cytokine profiles of the CD4 T cells define their functional subsets. The most distinct subsets of CD4 T cells are the type I and type II T helper cells (Th1 and Th2 cells). It appears that Th1 cells promote destructive inflammatory responses whereas Th2 cells promote humoral immune responses. Both Th1 and Th2 cells are derived from naïve CD4 T cells after antigenic stimulation.

My lab is interested in the molecular events that lead to the differentiation of Th1 and Th2 cells from naïve CD4 T cells. We have isolated genes differentially expressed in either Th1 or Th2 cells by using representational difference analysis (RDA). One of the Th2-specific genes is the transcription factor GATA-3. We have shown that high levels of GATA-3 are essential for the expression of Th2 cytokines, and Th1 lineage cells from mice transgenic for GATA-3 ectopically produce Th2 cytokines. On the other hand, a homeobox transcription factor Hlx is specifically expressed in Th1 cells. In mice transgenic for Hlx, there an increase in the number of Th1 cells, and the levels of IFN-gamma were elevated (total levels, and levels per individual T cell). Thus, Hlx and GATA-3 play causative roles in the differentiation of Th1 and Th2 cells, respectively.

Future work will focus on DNA-protein and protein-protein interactions related to these two transcription factors that are important in the establishment and maintenance of the Th1 and/or Th2 phenotypes. We will also characterize the functions of the other subset-specific genes using molecular, cellular and biochemical approaches. The ultimate goal of these studies is to provide a clear picture of the molecular pathways that lead to the differentiation and functional activation of Th1 and Th2 cells.

Publications

Zhao X, Zheng B, Huang Y, Yang D, Katzman S, Chang C, Fowell D, Zeng WP. Interaction between GATA-3 and the Transcriptional Coregulator Pias1 Is Important for the Regulation of Th2 Immune Responses. J Immunol. 2007 Dec 15;179(12):8297-304

Hamalainen-Laanaya HK, Kobie JJ, Chang C, Zeng WP. Temporal and spatial changes of histone 3 K4 dimethylation at the IFN-gamma gene during Th1 and Th2 cell differentiation. J Immunol. 2007 Nov 15;179(10):6410-5.

Mikhalkevich N, Becknell B, Caligiuri MA, Bates MD, Harvey R, Zheng WP. Responsiveness of naive CD4 T cells to polarizing cytokine determines the ratio of Th1 and Th2 cell differentiation. J Immunol. 2006 Feb 1;176(3):1553-60.

Young N, Mikhalkevich N, Yan Y, Chen D, Zheng WP. Differential regulation of osteoblast activity by Th cell subsets mediated by parathyroid hormone and IFN-gamma. J Immunol. 2005 Dec 15;175(12):8287-95.

Zheng WP, Zhao Q, Zhao X, Li B, Hubank M, Schatz DG, Flavell RA. Up-Regulation of Hlx in Immature Th Cells Induces IFN-gamma Expression. J Immunol. 172:114-122, 2004.

Lu B, Yu H, Chow C, Li B, Zheng W, Davis RJ, Flavell RA. GADD45gamma mediates the activation of the p38 and JNK MAP kinase pathways and cytokine production in effector TH1 cells. Immunity. 14:583-90, 2001.

Li B, Yu H, Zheng W, Voll R, Na S, Roberts AW, Williams DA, Davis RJ, Ghosh S, Flavell RA. Role of the guanosine triphosphatase Rac2 in T helper 1 cell differentiation. Science 288:2219-22, 2000.

Flavell RA, Rincon M, Zheng WP, Li B, Enslen H, Raingeaud J, Davis RJ. The regulation of CD4 T cell differentiation. Eur Cytokine Netw. 1998 Sep;9(3 Suppl):26-32. Review.

Zheng W, Flavell RA. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell 89:587-96, 1997.

Zheng WP, Kiura K, Milisauskas V, Nakamura I. Murine NK cell allospecificity-1 is defined by inhibitory ligands. J Immunol 156:4651-4655, 1996.

Zheng WP, Kiura K, Nakamura I. Dd is the only gene that controls NK cell resistance of heterozygous H-2b/d cells. Mol Immunol 32:773-776, 1995.

Zheng WP, Nakamura I. Immunological screening of homologous recombination in genes that encode surface antigens. BioTechniques 18:740-742, 1995.

Zheng WP, Milisauskas V, Nakamura I. Possible positive recognition of class I MHC molecule H-2Dd by natural killer cells. Natural Immunity 14:67, 1995.