Laboratory of Molecular Immunology and Cell Signaling

DESCRIPTION OF RESEARCH WORK

The Xiao lab leverages on a high throughput, antibody-guided, fusion-based drug discovery platform to investigate and identify broad spectrum anti-viral fusion inhibitors. Specifically, flavivirus infections, including dengue, is one of the most widely spread vector-born infectious diseases in tropical and sub-tropical area.

There is no effective therapeutics to date. Lack of successful drug candidates can largely be attributed to two reasons:

1) Inefficient preclinical animal model for therapeutics development;

2) Lack of new druggable targets that can inhibit virus mechanism-of-action.

There is a dire need for an improved approaches to develop curative anti-viral agents. Using a combination of high throughput small molecule drug screening, biochemical and structural biology approaches including Cryo-EM and NMR, as well as animal in vivo studies utilizing zebrafish and mice viral infectious models, we will search for small molecule inhibitors that can block virus/host membrane fusion. 

LEAD PI
Xiao Tianshu
Assistant Professor

Email: tianshu.xiao@ntu.edu.sg

 

  1. Drug discovery for broad-spectrum flavivirus fusion inhibitor
  2. Develop in vitro and in vivo tools to characterize viral entry and infection. 
  • Zhang J, Cai Y, Lavine CL, Peng H, Zhu H, Anand K, Tong P, Gautam A, Mayer ML, Rits-Volloch S, Wang S, Sliz P, Wesemann DR, Yang W, Seaman MS, Lu J, Xiao T and Chen B. Structural and functional impact by SARS-CoV-2 Omicron spike mutations. Cell Rep. 2022 Apr 26;39(4):110729.
  • Chen Y, Tong P, Whiteman N, Moghaddam AS, Zarghami M, Zuiani A, Habibi S, Gautam A, Keerti F, Bi C, Xiao T, Cai Y, Chen B, Neuberg D, Wesemann DR. Immune recall improves antibody durability and breadth to SARS-CoV-2 variants. Sci Immunol. 2022 May 12;eabp8328.
  • Zhang J*, Xiao T*, Cai Y, Lavine CL, Peng H, Zhu H, Anand K, Tong P, Gautam A, Sterling SM, Walsh RM Jr, Rits-Volloch S, Wesemann DR, Yang W, Seaman MS, Lu J, Chen B. Membrane fusion and immune evasion by the spike protein of SARS-CoV-2 Delta variant. Science. 2021 Dec 10;374(6573):1353-1360.
  • Cai Y*, Zhang J*, Xiao T*, Lavine CL, Rawson S, Peng H, Zhu H, Anand K, Tong P, Gautam A, Lu S, Sterling SM, Walsh RM Jr, Rits-Volloch S, Lu J, Wesemann DR, Yang W, Seaman MS, Chen B. Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 variants. Science. 2021 Aug 6;373(6555):642-648.
  • Xiao T, Lu J, Zhang J, Johnson RI, McKay LGA, Storm N, Lavine CL, Peng H, Cai Y, Rits-Volloch S, Lu S, Quinlan BD, Farzan M, Seaman MS, Griffiths A, Chen B. A trimeric human angiotensin-converting enzyme 2 as an anti-SARS-CoV-2 agent. Nat Struct Mol Biol. 2021 Feb;28(2):202-209.
  • Zhao P, Praissman JL, Grant OC, Cai Y, Xiao T, Rosenbalm KE, Aoki K, Kellman BP, Bridger R, Barouch DH, Brindley MA, Lewis NE, Tiemeyer M, Chen B, Woods RJ, Wells L. Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor. Cell Host Microbe. 2020 Oct 7;28(4):586-601.e6.
  • Cai Y, Zhang J, Xiao T, Peng H, Sterling SM, Walsh RM Jr, Rawson S, Rits-Volloch S, Chen B. Distinct conformational states of SARS-CoV-2 spike protein. Science. 2020 Sep 25;369(6511):1586-1592.
  • Piai A, Fu Q, Cai Y, Ghantous F, Xiao T, Shaik MM, Peng H, Rits-Volloch S, Chen W, Seaman MS, Chen B, Chou JJ. Structural basis of transmembrane coupling of the HIV-1 envelope glycoprotein. Nat Commun. 2020 May 8;11(1):2317.
  • Xiao T, Frey G, Fu Q, Lavine CL, Scott DA, Seaman MS, Chou JJ, Chen B. HIV-1 fusion inhibitors targeting the membrane-proximal external region of Env spikes. Nat Chem Biol. 2020 May;16(5):529-537.