Cui, J, Ding, Y, Chen, S, Zhu, X, Wu, Y, Zhang, M, Zhao, Y, Li, T-RR, Sun, LV, Zhao, S, Zhuang, Y, Jia, W, Xue, L, Han, M, Xu, T, and Wu, X. "Disruption of Gpr45 causes reduced hypothalamic POMC expression and obesity." The Journal of clinical investigation 126, no. 9 (September 2016): 3192-3206.
Yuan Zhuang, PhD
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
- Organization and Function of Cellular Structure
- Basic Immunology Training Program
- Genetic dissection of Id3-mediated pathways in lineage development
- E2A/HEB TRANSCRIPTION FACTORS IN T CELL DEVELOPMENT
- 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
- 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
Zhang, B, Jia, Q, Bock, C, Chen, G, Yu, H, Ni, Q, Wan, Y, Li, Q, and Zhuang, Y. "Glimpse of natural selection of long-lived T-cell clones in healthy life." Proceedings of the National Academy of Sciences of the United States of America 113, no. 35 (August 17, 2016): 9858-9863.
Ye, Z, Sun, L, Li, R, Han, M, Zhuang, Y, Wu, X, and Xu, T. "Generation of a Mouse Full-length Balancer with Versatile Cassette-shuttling Selection Strategy." International journal of biological sciences 12, no. 8 (January 2016): 911-916.
Zhang, B, Wu, J, Jiao, Y, Bock, C, Dai, M, Chen, B, Chao, N, Zhang, W, and Zhuang, Y. "Differential Requirements of TCR Signaling in Homeostatic Maintenance and Function of Dendritic Epidermal T Cells." Journal of immunology (Baltimore, Md. : 1950) 195, no. 9 (November 2015): 4282-4291.
Ye, J, Shi, H, Shen, Y, Peng, C, Liu, Y, Li, C, Deng, K, Geng, J, Xu, T, Zhuang, Y, Zheng, B, and Tao, W. "PP6 controls T cell development and homeostasis by negatively regulating distal TCR signaling." Journal of immunology (Baltimore, Md. : 1950) 194, no. 4 (February 2015): 1654-1664.
Roy, S, and Zhuang, Y. "Orchestration of invariant natural killer T cell development by E and Id proteins." Critical reviews in immunology 35, no. 1 (January 2015): 33-48. (Review)
Belle, I, Mahlios, J, McKenzie, A, and Zhuang, Y. "Aberrant production of IL-13 by T cells promotes exocrinopathy in Id3 knockout mice." Cytokine 69, no. 2 (October 2014): 226-233.
Niola, F, Zhao, X, Singh, D, Sullivan, R, Castano, A, Verrico, A, Zoppoli, P, Friedmann-Morvinski, D, Sulman, E, Barrett, L, Zhuang, Y, Verma, I, Benezra, R, Aldape, K, Iavarone, A, and Lasorella, A. "Mesenchymal high-grade glioma is maintained by the ID-RAP1 axis." The Journal of clinical investigation 124, no. 9 (September 2014): 4134-.
Zhang, B, Lin, Y-Y, Dai, M, and Zhuang, Y. "Id3 and Id2 act as a dual safety mechanism in regulating the development and population size of innate-like γδ T cells." J Immunol 192, no. 3 (February 1, 2014): 1055-1063.
Li, J, Wu, D, Jiang, N, and Zhuang, Y. "Combined deletion of Id2 and Id3 genes reveals multiple roles for E proteins in invariant NKT cell development and expansion." J Immunol 191, no. 10 (November 15, 2013): 5052-5064.
Zhang, B, Dai, M, Li, Q-J, and Zhuang, Y. "Tracking proliferative history in lymphocyte development with cre-mediated sister chromatid recombination." PLoS Genet 9, no. 10 (October 2013): e1003887-.
Lin, Y-Y, Jones-Mason, ME, Inoue, M, Lasorella, A, Iavarone, A, Li, Q-J, Shinohara, ML, and Zhuang, Y. "Transcriptional regulator Id2 is required for the CD4 T cell immune response in the development of experimental autoimmune encephalomyelitis." J Immunol 189, no. 3 (August 1, 2012): 1400-1405.
Zhu, Y, Liu, S, Yin, Q, Xu, T, Wu, X, and Zhuang, Y. "Generation of Dhx9-deficient clones in T-cell development with a mitotic recombination technique." Genesis 50, no. 7 (July 2012): 543-551.
Jones-Mason, ME, Zhao, X, Kappes, D, Lasorella, A, Iavarone, A, and Zhuang, Y. "E protein transcription factors are required for the development of CD4(+) lineage T cells." Immunity 36, no. 3 (March 23, 2012): 348-361.
Mahlios, J, and Zhuang, Y. "Contribution of IL-13 to early exocrinopathy in Id3-/- mice." Mol Immunol 49, no. 1-2 (October 2011): 227-233.