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 includingCell Host & Microbe, EMBO J, JEM, PNAS, NatureandScience.

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.