Greater Bay Biomedical InnoCenter
Junior Principal Investigator
2022 - Present
Shenzhen Bay Laboratory Junior Principal Investigator
Dr. Dan Littman's lab, HHMI, Skirball institute, New York University Postdoctoral Fellow
National Institute of Biological Sciences, Beijing, Dr. Feng Shao's Lab Postdoctoral Fellow
National Institute of Biological Sciences, Beijing/Beijing Normal University Ph.D.
Huazhong Agricultural University BS
1) To employ different autoimmune disease models to study the fates and functions of Treg cells and the crosstalk between Treg cells and various tissue microenvironments.
2) To explore the Treg-mediated immune therapy for autoimmune diseases.
3) To understand the versatile roles and mechanisms of TGF-β in regulation of the development of different immune cells.
Dr. Xu received Ph.D. training on innate immunity in Dr. Feng Shao’s lab at National Institute of Biological Science (NIBS), where he published multiple works revealing evolved pathogen-host interactions engaged by bacterial and host molecules. For example, OspF, an effector protein secreted by pathogenic Shigella species, employs a novel phosphothreonine lyase activity to inhibit the host MAPK pathway, which is linked to the anti-bacterial inflammation (Science, 2007). On the other hand, hosts evolve to sense the post-translational modifications and inactivation of Rho family proteins caused by bacterial infection through Pyrin proteins, resulting the activation of inflammasome to suppress bacterial growth in vivo. This work first defines the Pyrin protein as a new pattern recognition receptor and a new Pyrin-mediated signal cascade to activate inflammasome (Nature, 2014). To expand the study holistically, Dr. Xu joined Dr. Dan Littman lab at New York University for postdoctoral research on adaptive immunity, where he studied the functions and regulations of Type 17 T-helper (Th17) and induced T regulatory (iTreg) cells. Partial of his work reveals that the E3 ligase Arkadia, a component involved in TGF-β signaling, is selectively required for the differentiation of iTreg but not Th17 cells both in vitro and in vivo (JEM, 2021). This work further dissect the development of iTreg and Th17 cells downstream of TGF-β signaling, which is indispensable for both cells differentiation. Dr. Xu has multiple publications as first author or co-first author including Cell Host & Microbe, EMBO J, JEM, PNAS, Nature and Science.
The modification of Rho family proteins could be induced by bacteria or host pathology. The resulting danger signals are detected by a novel pattern recognition receptor, Pyrin, and trigger the activation of inflammasome.
In response to TGF-β stimuli, Arkadia induces the degradation of SMAD proteins-bound SKI and SnoN, resulting the inactivation of HDAC and maintenance of histone acetylation. SMADs-medated transcriptional complexes further promote the expression of Foxp3.
1. Cancer Research Institute (CRI) Irvington Postdoctoral Fellowship, 2016-2019, Cancer Research Institute
2. Travel support, 2014, the 4th Asia Pacific Protein Association Conference
3. Poster award, 2014, the 4th Asia Pacific Protein Association Conference
4. Outstanding Graduate Student, 2011, National Institute of Biological Sciences, Beijing
1. Hao Xu, Lin Wu, Henry Nguyen, Kailin R. Mesa, Varsha Raghavan, Vasso Episkopou, Dan R. Littman (2021), Arkadia-SKI/SnoN signaling differentially regulates TGF-β-induced iTreg and Th17 cell differentiation, J Exp Med, 218 (11): e20210777.
2. Daniel F.Aubert*, Hao Xu*, Jieling Yang, Xuyan Shi, Wenqing Gao, Lin Li, Fabiana Bisaro, She Chen, Miguel A.Valvano, Feng Shao (2016). A Burkholderia type VI effector deamidates Rho GTPases to activate the pyrin inflammasome and trigger inflammation, Cell Host & Microbe, 19(5), 664-674. (*co-first author)
3. 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. (*co-first author)
4. Hongtao Li*, Hao Xu*, Yan Zhou*, Jie Zhang, Chengzu Long, Shuqin Li, She Chen, JianMin Zhou, Feng Shao (2007). The Phosphothreonine Lyase Activity of a Bacterial Type III Effector Family, Science, 315, 1000-1003. (*co-first author)