Prof. Biao Zheng

E-mail: bzheng@bio.ecnu.edu.cn

Dr. Biao Zheng graduated with a Bachelor of Medicine from Zhejiang University School of Medicine. He got his MS in Immunology from Fudan University School of Medicine and PhD in Immunology from University of London, respectively. Dr. Zheng served at the faculty of University of Maryland School of Medicine and Duke University Medical center before he joined the Department of Immunology, Baylor College of Medicine in 1999.  He was appointed tenured Associate Professor of Immunology at Baylor College of Medicine in 2006. Dr. Zheng joined GSK R&D China in 2010 as the director of the Discovery Sciences research group. He joined School of Life Sciences at ECNU in 2014.

Research Interests:

Immune regulation; Development and Genetics of the Immune Responses; Autoimmunity; Vaccine development

Dr. Zheng has been studying the molecular and cellular bases for the fundamental properties of an effective immune response, such as specificity, affinity, and memory using the techniques of cell and molecular biology, and in vitro and in vivo models of immune responses. In addition, his research extends to understand the pathology of autoimmune diseases and novel vaccine development. On-going work in this laboratory has focused on the following topics.

Antigen-driven Lymphocyte Differentiation. Antigen-specific T- and B cells interact with each other in complex and dynamic microenvironments, and these interactions regulate their differentiation into different functional cells. Our research focuses on the somatic genetics of antigen-specific lymphocytes, which includes clonal analysis of antigen-receptor repertoires during in vivo immune responses; determination of the relationship between particular phenotypes of lymphocytes and their genotypes; and reconstruction of population structure of immune responses in situ. Using ex vivo and in situ cellular and molecular approaches, we have been able to follow the activation, selection, and differentiation of antigen-specific lymphocytes as an immune response develops in vivo. Further efforts will be made to elucidate the functions of lymphocytes from various compartments in the peripheral lymphoid tissues at distinct stages of immune responses such as memory and tolerance.

Germinal Center Biology. After their activation by antigen in secondary lymphoid tissues, antigen-specific T- and B-lymphocytes form a transient histologic structure known as the germinal center (GC) in the follicular dendritic cell reticulum. GCs represent a remarkable lymphoid microenvironment that functions to expand and diversify antigen-reactive clones. We have been interested in the molecular and cellular processes during the GC reaction, which is a focus of intense cellular proliferation, V(D)J hypermutation, and apoptotic death. Indeed, GCs are microcosms of Darwinian evolution that share many of the processes usually thought to occur only during primary lymphopoiesis , including positive and negative selection, elimination of self-reactive cells, and generation and enrichment of the high affinity, memory compartments. Our work has suggested GC reaction as a new development and differentiation pathway for peripheral lymphocytes. Currently, this laboratory is studying the molecular events that are involved in V(D)J hypermutation, receptor editing, and the development of memory compartments in the GC.

Autoimmunity. In addition to peripheral lymphoid tissues, the lymphocytic infiltrates present in various autoimmune diseases also form GC-like structures. In patients with rheumatoid arthritis (RA), the synovial membrane or subchondral bone of the arthritic joints is infiltrated with T- and B lymphocytes organized into structures that are similar to the GCs present in peripheral lymphoid tissues. V(D)J hypermutation, development of plasmacytes and generation of memory cells in this GC-like environment indicate that this response is part of the chronic process of this immune-mediated disease. However, the role of GC reaction in the pathogenesis of RA has never been adequately addressed, because GCs formed in the affected joints of RA patients cannot be readily studied. This laboratory has, for the first time, induced de novo GC formation in inflamed joints in a mouse model with collagen-induced arthritis (CIA). Our goal is to understand the role of GC reaction in the initiation and progression of autoimmune arthritis. This study will also provide new insight into identification of potential targets for immunological intervention.

Representative Publications:

• Zheng, B., S Brett, J Tite, MR Lifely, TA Brodie, and J Rhodes. (1992) Galactose Oxidation in the Design of Immunogenetic Vaccines. Science, 256:1560.
•  Zheng, B., Xue, W. and Kelsoe, G. (1994) Locus-specific Somatic Hypermutation in Germinal Center T Cells. Nature, 372:556.
• Rhodes, J., Chen, H., Hall, S. R., Beesley, J. E., Jenkins, D. C., Collins, P. and Zheng, B. (1995) Therapeutic Potentiation of the Immune System by Costimulatory Schiff Base-forming Drugs. Nature, 377:71.
• Zheng, B., Han, S., Zhu, Q., Goldsby, R., Kelsoe, G. (1996) Alternative pathways for the antigen-specific selection of peripheral T cells. Nature, 384:263.
• Han, S, B Zheng, DG Schatz, E Spanopoulou, G Kelsoe (1996) Neoteny in lymphocytes: Rag1 and Rag 2 expression in germinal center B cells. Science, 274:2094.
• Han, S-H., Dillion, S., Zheng, B. Schlissel, M., and Kelsoe, G. (1997) V(D)J Recombinase Activity in a Subset of Germinal Center B Lymphocytes. Science, 278:301.
• Han, S., Guan, H., Wang, G., Li, P., Feng, L., and Zheng, B. (2004) FYT720 inhibits humoral immunity by suppressing germinal center reaction. Blood, 104:4129.
• Marinova, E., Han, S., and Zheng, B. (2007) Germinal center helper T-cells are dual functional regulatory cells with suppressive activity to conventional CD4⁺ T-cells. J. Immunol. 178:5010.
• Voo, K.S., Y. Wang Y, F. Santori, S. Hanabuchi, E. Marinova, B. Zheng, D.R. Littman, Y.J. Liu. (2009) Identification of IL-17-producing FOXP3+ regulatory T cells in humans. Proc Natl Acad Sci USA 106:4793-4798.
• Chen. L., J. Tian, H. He, K. Switzer, P. Zhang, B. Zheng and S. Han.  (2010) Over-expression of CXCL14 exacerbates collagen-induced arthritis via promoting T cell response. J. Immunol. 184:4455-4459.
• Zhang Q, Cui F, Fang L, Hong J, Zheng B, and Zhang JZ. (2013) TNF-α impairs differentiation and function of TGF-β-induced Treg cells in autoimmune diseases through Akt and Smad3 signaling pathway. J Mol Cell Biol 5: 85.
• Du X, Shi H, Li J, Dong Y, Liang J, Ye J, Kong S, Zhang S, Zhong T, Yuan Z, Xu T, Zhuang, Y, Zheng B, Geng J, and Tao W. (2014) st1/Mst2 regulate development and function of regulatory T cells through modulation of Foxo1/Foxo3 stability in autoimmune disease. J. Immunol. 192:1525