Hao Xu, PhD
Cancer Research Institute (CRI) Postdoctoral Fellow
PhD National Institute of Biological Sciences, Beijing, China, 2014
My PhD work mainly focused on the biochemical mechanism behind inflammasome activation and its biological function. I was particularly interested in the fundamental discovery of exogenous or intracellular ligands that trigger inflammasome activation, as well as their corresponding cytosolic pattern recognition receptors and signal transduction. Through the reconstitution of this pathway in non-immune cells, the inflammasome can be studied more easily in cell types that are more easily manipulated than immune cells and do not otherwise display endogenous inflammasome activity. Using this reconstitution system, we discovered that a non-typical NLR protein, Pyrin, senses the shut-down of Rho small GTpases, which would go on to activate the inflammasome. Pyrin, which is encoded by the MEFV gene, is well known for its mutations that cause an autoinflammatory disease, Familial Mediterranean Fever (FMF). This research defined the physiological role of Pyrin. Interestingly, TcdA and TcdB, critical disease causing toxins secreted by Clostridium difficile, a rampant nosocomial infectious agent, specifically activate the Pyrin inflammasome by inactivating Rho small GTpases.
I was drawn to the Littman lab because of their focus on the basic science underlying adaptive immunity, which responds to signals initiated by the innate immune system. Expanding my research within the adaptive immune system, I hope to combine an understanding of the various arms of the immune system and global immune responses to better understand autoimmunity and autoinflammatory disease.
1. Hao Xu*, Jieling Yang*, Wenqing Gao, Lin Li, Peng Li, Li Zhang, Yi-Nan Gong, Xiaolan Peng, Jianzhong Jeff Xi, She Chen, Fengchao Wang & Feng Shao (2014). Innate immune sensing of bacterial modifications of Rho GTPases by the Pyrin inflammasome, Nature, 513, 237–241
2. Yue Zhao, Jieling Yang, Jianjin Shi, Yi-Nan Gong, Qiuhe Lu, Hao Xu, Liping Liu & Feng Shao (2011). The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus, Nature, 477, 596-600
3. Ge J*, Hao Xu*, Li T, Zhou Y, Zhang Z, Li S, Liu L, Shao F (2009). A Legionella type IV effector activates the NF-κB pathway by phosphorylating the IκB family of inhibitors. Proc. Natl. Acad. Sci., 106, 13725-13730 (co-first author)
4. Hongtao Li*, Hao Xu*, Yan Zhou*, Jie Zhang, Chengzu Long, Shuqin Li, She Chen, Jian-Min Zhou, Feng Shao (2007). The Phosphothreonine Lyase Activity of a Bacterial Type III Effector Family, Science, 315, 1000-1003 (co-first author)
5. Yongqun Zhu, Hongtao Li, Chengzu Long, Liyan Hu, Hao Xu, Liping Liu, She Chen, Da-Cheng Wang, Feng Shao (2007). Structural Insights into the Enzymatic Mechanism of the Pathogenic MAPK Phosphothreonine Lyase, Molecular Cell, 28, 899-913