|Dr. Huayi Wang graduated from Department of Biology of Nanjing University in 2002 and received Ph.D. degree in structure biology from National Institute of Biological Sciences/Peking Union Medical College in 2008. Then he went to UT Southwestern Medical Center at Dallas as a postdoctoral fellow to study the programmed necrosis. In 2010, he transferred back to the National Institute of Biological Sciences and continue his study. Since December of 2014, he joined the School of Life Science and Technology of ShanghaiTech University as assistant professor (Tenure-track), PI.|
|RIP3 kinase-mediated programmed necrosis, also known as necroptosis, plays pivotal roles in many biological processes such as development, innate immune response to infection and pathogenesis of many degenerative diseases. In the case of TNFR1 activation, the most studied model of necroptosis, necrotic cell death depends on the kinase activity of both RIP1 and RIP3. A pseudo-kinase MLKL, the substrate of the RIP3 will serve as the necrosis executioner. In vivo necroptosis functions to eliminate unhealthy cells that are either damaged or infected with pathogens, which in turn induces immune response to monitor the damaged or infected areas (of tissues). Excessive necrotic cell death has been associated with secondary damage in liver, kidney, brain and cardiac tissues after initial injury by chemicals, calcium overload or ischemia reperfusion in different disease models. |
Our lab will focus on functional mechanism of necrosis signaling in degenerative diseases programming. We will further dissect the signaling pathways of necrosis in pathogenesis by combining a variety of different approaches, especially using unique chemical tools, and study the structural and biophysical basis of the critical steps in these signaling pathways.
|1. Li, D., Xu, T., Cao, Y., Wang, H., Li, L., Chen, S., Wang, X., and Shen, Z. (2015). A cytosolic heat shock protein 90 and cochaperone CDC37 complex is required for RIP3 activation during necroptosis. Proc Natl Acad Sci U S A，112, 5017-5022.|
2. Su, L., Quade, B., Wang, H., Sun, L., Wang, X., and Rizo, J. (2014). A plug release mechanism for membrane permeation by MLKL. Structure, 22, 1489-1500.
3. Wang, H., Sun, L., Su, L., Rizo, J., Liu, L., Wang, LF., Wang, FS., and Wang, X. (2014) Mixed Lineage Kinase Domain-like protein MLKL Causes Necrotic Membrane Disruption Upon Phosphorylation by RIP3. Mol Cell, 54, 133-146.
(Selected as the Cover Story of Mol Cell; Story of this work was selected by Faculty of 1000 Biology.)
4. Sun, L., Wang, H., Wang, Z., He, S., Chen, S., Liao, D., Wang, L., Yan, J., Liu, W., Lei, X., and Wang, X. (2012) Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell, 148, 213-227.
5. Sun, L., Wang, H., Hu, J., Han, J., Matsunami, H., and Luo, M. (2009). Guanylyl cyclase-D in the olfactory CO2 neurons is activated by bicarbonate. Proc Natl Acad Sci U S A, 106, 2041-2046.
6. Liang, P.*, Wang, H.*, Chen, H.*, Cui, Y., Gu, L., Chai, J., and Wang, K. (2009). Structural Insights into KChIP4a Modulation of Kv4.3 Inactivation. The Journal of biological chemistry, 284, 4960-4967. （*Equal contribution）
7. Chen, L.*, Wang, H.*, Zhang, J., Gu, L., Huang, N., Zhou, J.M., and Chai, J. (2008). Structural basis for the catalytic mechanism of phosphothreonine lyase. Nature structural & molecular biology, 15, 101-102. （*Equal contribution）
8. Wang, H.*, Yan, Y.*, Liu, Q., Huang, Y., Shen, Y., Chen, L., Chen, Y., Yang, Q., Hao, Q., Wang, K., et al. (2007). Structural basis for modulation of Kv4 K+ channels by auxiliary KChIP subunits. Nature neuroscience, 10, 32-39. （*Equal contribution）
9. Han, Z., Guo, L., Wang, H., Shen, Y., Deng, X.W., and Chai, J. (2006). Structural basis for the specific recognition of methylated histone H3 lysine 4 by the WD-40 protein WDR5. Molecular cell, 22, 137-144.
10. Zhang, T., Sun, Y., Tian, E., Deng, H., Zhang, Y., Luo, X., Cai, Q., Wang, H., Chai, J., and Zhang, H. (2006). RNA-binding proteins SOP-2 and SOR-1 form a novel PcG-like complex in C. elegans. Development, 133, 1023-1033.