Ko, Annette, Masashi Watanabe, Thomas Nguyen, Alvin Shi, Achouak Achour, Baojun Zhang, Xiaoping Sun, et al. “TCR Repertoires of Thymic Conventional and Regulatory T Cells: Identification and Characterization of Both Unique and Shared TCR Sequences.” J Immunol 204, no. 4 (February 15, 2020): 858–67. https://doi.org/10.4049/jimmunol.1901006.
Yuan Zhuang, PhD
Professor of Immunology
Campus Mail:
328 Jones Building, 207 Resear, Box 3010 DUMC, Durham, NC 27710
Phone:
(919) 613-7824
Email:
yzhuang@duke.edu
Research in our laboratory focuses on molecular mechanism of lymphocyte development and genetic basis of lymphoid diseases such as leukemia and autoimmune disorders. We are using mouse models to investigate the role of E2A and other related transcription factors in lymphocyte development and immune function. We have shown that E2A plays an essential role in regulating both B and T cell development. Mice deficient for E2A cannot produce any B cell and exhibit high incidence of T cell leukemia. Separate studies also indicated that E2A is involved in the development of autoimmune disorders. Our current and future studies are to combine genetic, molecular biology, and immunology means to determine gene expression programs during lymphocyte development.
The mechanistic studies of gene function in animal models provide important clues in understanding relevant human diseases. It has been shown that about 20-30% of pediatric acute lymphocytic leukemias (ALL) are linked to chromosomal rearrangements at the E2A gene locus. Most of these genetic defects produce oncogenic forms of E2A proteins, which are the possible cause of leukemia. The use of animal models allows us to further define the molecular events underlying the disease development. Our long term goal is to provide molecular basis for early diagnosis and treatment of relevant lymphoid system diseases.
Laboratory website: Http://sites.duke.edu/zhuanglab.
Education and Training
- Ph.D., Yale University, 1989
Selected Grants and Awards
- Basic Immunology Training Program
- E2A/HEB MEDIATED TRANSCRIPTIONAL REGULATION IN T CELL DEVELOPMENT
- Regulation of the type 1 program during ILC3 plasticity
- Organization and Function of Cellular Structure
- Molecular and genomic control of innate gd T cell development
- A New Method for Mosaic Analysis of Clonal Mutations in Mice
- Training Program in Inflammatory and Immunological Diseases
- A new approach to homeostatic maintenance of dendritic epidermal T cells
- Cancer Biology Training Grant
- A New Genetic Tool for Lineage Tracing of Mitotic Cells in Mice
- An episomal marking system for tracking cell proliferation in development, tissue homeostasis, and ageing
- Functions of E2A in B Lymphocyte Development
- Modeling Sjogrens Syndrome with Id3 Conditional Knockout Mice
- Orphan Nuclear Receptor in Thymocyte Differentiation
- The Functions Of E2a In B-Lymphocyte Development
- Cancer Center Core Support Grant
- Comprehensive Cancer Center Core Support Grant
Selected Publications
Panea, Razvan I., Cassandra L. Love, Jennifer R. Shingleton, Anupama Reddy, Jeffrey A. Bailey, Ann M. Moormann, Juliana A. Otieno, et al. “The whole-genome landscape of Burkitt lymphoma subtypes.” Blood 134, no. 19 (November 7, 2019): 1598–1607. https://doi.org/10.1182/blood.2019001880.
Kadakia, Tejas, Xuguang Tai, Michael Kruhlak, Jan Wisniewski, Il-Young Hwang, Sumedha Roy, Terry I. Guinter, et al. “E-protein-regulated expression of CXCR4 adheres preselection thymocytes to the thymic cortex.” J Exp Med 216, no. 8 (August 5, 2019): 1749–61. https://doi.org/10.1084/jem.20182285.
Sandrock, Inga, Annika Reinhardt, Sarina Ravens, Christoph Binz, Anneke Wilharm, Joana Martins, Linda Oberdörfer, et al. “Genetic models reveal origin, persistence and non-redundant functions of IL-17-producing γδ T cells.” J Exp Med 215, no. 12 (December 3, 2018): 3006–18. https://doi.org/10.1084/jem.20181439.
Roy, Sumedha, and Yuan Zhuang. “Paradoxical role of Id proteins in regulating tumorigenic potential of lymphoid cells.” Front Med 12, no. 4 (August 2018): 374–86. https://doi.org/10.1007/s11684-018-0652-x.
Roy, Sumedha, Amanda J. Moore, Cassandra Love, Anupama Reddy, Deepthi Rajagopalan, Sandeep S. Dave, Leping Li, Cornelis Murre, and Yuan Zhuang. “Id Proteins Suppress E2A-Driven Invariant Natural Killer T Cell Development prior to TCR Selection.” Front Immunol 9 (2018): 42. https://doi.org/10.3389/fimmu.2018.00042.
Carico, Zachary M., Kingshuk Roy Choudhury, Baojun Zhang, Yuan Zhuang, and Michael S. Krangel. “Tcrd Rearrangement Redirects a Processive Tcra Recombination Program to Expand the Tcra Repertoire.” Cell Rep 19, no. 10 (June 6, 2017): 2157–73. https://doi.org/10.1016/j.celrep.2017.05.045.
Li, Jia, Sumedha Roy, Young-Mi Kim, Shibo Li, Baojun Zhang, Cassandra Love, Anupama Reddy, et al. “Id2 Collaborates with Id3 To Suppress Invariant NKT and Innate-like Tumors.” J Immunol 198, no. 8 (April 15, 2017): 3136–48. https://doi.org/10.4049/jimmunol.1601935.
McKinney, Matthew, Andrea B. Moffitt, Philippe Gaulard, Marion Travert, Laurence De Leval, Alina Nicolae, Mark Raffeld, et al. “The Genetic Basis of Hepatosplenic T-cell Lymphoma.” Cancer Discov 7, no. 4 (April 2017): 369–79. https://doi.org/10.1158/2159-8290.CD-16-0330.
Cui, Jing, Yi Ding, Shu Chen, Xiaoqiang Zhu, Yichen Wu, Mingliang Zhang, Yaxin Zhao, et al. “Disruption of Gpr45 causes reduced hypothalamic POMC expression and obesity.” J Clin Invest 126, no. 9 (September 1, 2016): 3192–3206. https://doi.org/10.1172/JCI85676.
Zhang, Baojun, Qingzhu Jia, Cheryl Bock, Gang Chen, Haili Yu, Qingshan Ni, Ying Wan, Qijing Li, and Yuan Zhuang. “Glimpse of natural selection of long-lived T-cell clones in healthy life.” Proc Natl Acad Sci U S A 113, no. 35 (August 30, 2016): 9858–63. https://doi.org/10.1073/pnas.1601634113.
Ye, Zhisheng, Lei Sun, Rongbo Li, Min Han, Yuan Zhuang, Xiaohui Wu, and Tian Xu. “Generation of a Mouse Full-length Balancer with Versatile Cassette-shuttling Selection Strategy.” Int J Biol Sci 12, no. 8 (2016): 911–16. https://doi.org/10.7150/ijbs.15172.
Zhang, Baojun, Jianxuan Wu, Yiqun Jiao, Cheryl Bock, Meifang Dai, Benny Chen, Nelson Chao, Weiguo Zhang, and Yuan Zhuang. “Differential Requirements of TCR Signaling in Homeostatic Maintenance and Function of Dendritic Epidermal T Cells.” J Immunol 195, no. 9 (November 1, 2015): 4282–91. https://doi.org/10.4049/jimmunol.1501220.
Ye, Jian, Hao Shi, Ye Shen, Chao Peng, Yan Liu, Chenyu Li, Kejing Deng, et al. “PP6 controls T cell development and homeostasis by negatively regulating distal TCR signaling.” J Immunol 194, no. 4 (February 15, 2015): 1654–64. https://doi.org/10.4049/jimmunol.1401692.
Roy, Sumedha, and Yuan Zhuang. “Orchestration of invariant natural killer T cell development by E and Id proteins.” Crit Rev Immunol 35, no. 1 (2015): 33–48. https://doi.org/10.1615/critrevimmunol.2015012207.