Tsan Sam Xiao graduated from Zhejiang University in Hangzhou, China with a Bachelor's degree in Biological Sciences and Technology. He subsequently received a Master's degree in Developmental Biology from the Chinese Academy of Sciences in 1995. He then came to the US and studied the structures of death domains from the Drosophila proteins Pelle and Tube implicated in fly development and innate immunity, for which he received his Ph.D. in molecular biophysics at the University of Texas Southwestern Medical Center at Dallas in 2000. He continued his postdoctoral training with Dr. Timothy Springer at the Harvard Medical School focusing on cell adhesion receptors such as integrins and ICAMs, both of which play important roles in immune surveillance, thrombosis, and tumor metastasis. He established his own laboratory at NIH in 2006 investigating the structures of innate immune receptors, inflammasomes, and adapter molecules implicated in antimicrobial host defense and inflammatory disorders. Dr. Xiao joined the faculty at the Case Western Reserve University's Department of Pathology in 2014. The current focus of the Xiao lab is the molecular mechanism of pyroptosis, a highly inflammatory form of cell death; and modulation of inflammatory caspases using chemical biology approaches to target inflammatory disorders.
My research focuses on structural and function of gasdermin family members in pyroptosis and inflammatory cytokine secretion, Molecular mechanisms of inflammasome activation during viral infection such as SARS-CoV-2, and Activation and substrate recognition by inflammatory caspases in health and disease.
Research Information
Research Interests
The Xiao lab uses structural and chemical biology approaches to study the inflammasome signaling pathways, with the goal of targeting diverse diseases such as sepsis, multiple sclerosis, and AIDS using small molecule compounds.
For more information visit: Xiao Lab
Publications
Liu Z, Busscher BM, Storl-Desmond M, Xiao TS. Mechanisms of Gasdermin Recognition by Proteases. J Mol Biol. 2022 Feb 28;434(4):167274. doi: 10.1016/j.jmb.2021.167274. Epub 2021 Sep 29. Review. PubMed PMID: 34599940; PubMed Central PMCID: PMC8844061.
Liu Z, Xiao TS. Partners with a killer: Metabolic signaling promotes inflammatory cell death. Cell. 2021 Aug 19;184(17):4374-4376. doi: 10.1016/j.cell.2021.07.036. PubMed PMID: 34416144.
Liu Z, Wang C, Yang J, Chen Y, Zhou B, Abbott DW, Xiao TS. Caspase-1 Engages Full-Length Gasdermin D through Two Distinct Interfaces That Mediate Caspase Recruitment and Substrate Cleavage. Immunity. 2020 Jul 14;53(1):106-114.e5. doi: 10.1016/j.immuni.2020.06.007. Epub 2020 Jun 17. PubMed PMID: 32553275; PubMed Central PMCID: PMC7382298.
Srinivasan S, Liu Z, Chuenchor W, Xiao TS, Jankowsky E. Function of Auxiliary Domains of the DEAH/RHA Helicase DHX36 in RNA Remodeling. J Mol Biol. 2020 Mar 27;432(7):2217-2231. doi: 10.1016/j.jmb.2020.02.005. Epub 2020 Feb 19. PubMed PMID: 32087197; PubMed Central PMCID: PMC7225076.
Rathkey JK, Xiao TS, Abbott DW. Human polymorphisms in GSDMD alter the inflammatory response. J Biol Chem. 2020 Mar 6;295(10):3228-3238. doi: 10.1074/jbc.RA119.010604. Epub 2020 Jan 27. PubMed PMID: 31988247; PubMed Central PMCID: PMC7062166.
Liu Z, Wang C, Yang J, Zhou B, Yang R, Ramachandran R, Abbott DW, Xiao TS. Crystal Structures of the Full-Length Murine and Human Gasdermin D Reveal Mechanisms of Autoinhibition, Lipid Binding, and Oligomerization. Immunity. 2019 Jul 16;51(1):43-49.e4. doi: 10.1016/j.immuni.2019.04.017. Epub 2019 May 13. PubMed PMID: 31097341; PubMed Central PMCID: PMC6640092.
Rathkey JK, Zhao J, Liu Z, Chen Y, Yang J, Kondolf HC, Benson BL, Chirieleison SM, Huang AY, Dubyak GR, Xiao TS, Li X, Abbott DW. Chemical disruption of the pyroptotic pore-forming protein gasdermin D inhibits inflammatory cell death and sepsis. Sci Immunol. 2018 Aug 24;3(26). doi: 10.1126/sciimmunol.aat2738. PubMed PMID: 30143556; PubMed Central PMCID: PMC6462819.
Yang J, Liu Z, Wang C, Yang R, Rathkey JK, Pinkard OW, Shi W, Chen Y, Dubyak GR, Abbott DW, Xiao TS. Mechanism of gasdermin D recognition by inflammatory caspases and their inhibition by a gasdermin D-derived peptide inhibitor. Proc Natl Acad Sci U S A. 2018 Jun 26;115(26):6792-6797. doi: 10.1073/pnas.1800562115. Epub 2018 Jun 11. PubMed PMID: 29891674; PubMed Central PMCID: PMC6042100.
Liu Z, Wang C, Rathkey JK, Yang J, Dubyak GR, Abbott DW, Xiao TS. Structures of the Gasdermin D C-Terminal Domains Reveal Mechanisms of Autoinhibition. Structure. 2018 May 1;26(5):778-784.e3. doi: 10.1016/j.str.2018.03.002. Epub 2018 Mar 22. PubMed PMID: 29576317; PubMed Central PMCID: PMC5932255.
Yangyuoru PM, Bradburn DA, Liu Z, Xiao TS, Russell R. The G-quadruplex (G4) resolvase DHX36 efficiently and specifically disrupts DNA G4s via a translocation-based helicase mechanism. J Biol Chem. 2018 Feb 9;293(6):1924-1932. doi: 10.1074/jbc.M117.815076. Epub 2017 Dec 21. PubMed PMID: 29269411; PubMed Central PMCID: PMC5808756.
Perez JM, Chen Y, Xiao TS, Abbott DW. Phosphorylation of the E3 ubiquitin protein ligase ITCH diminishes binding to its cognate E2 ubiquitin ligase. J Biol Chem. 2018 Jan 19;293(3):1100-1105. doi: 10.1074/jbc.RA117.000408. Epub 2017 Dec 6. PubMed PMID: 29212706; PubMed Central PMCID: PMC5777250.