Jianbin Ruan, Ph.D.Assistant Professor of Immunology
- Education & Training
- Committees & Organizations
- Research Opportunities
- Lab Rotations
|B.S.||University of Science and Technology of China||Biotechnology|
|Ph.D.||University of Science and Technology of China||Structural Biology|
|Fellowship||Harvard Medical School, Boston Children's Hospital||Research|
|Name of Award/Honor||Awarding Organization|
|Charles A. King Trust Postdoctoral Research Fellowship|
|Zhuliyuehua Scholarship for Excellent Doctoral Student of Chinese Academy of Sciences|
|Dong Gang Scholarship for Outstanding Graduate Students of USTC|
|Second Prize of Excellent Undergraduate Scholarship|
|Name & Description||Category||Role||Type||Scope||Start Year||End Year|
|Molecular Aspects of Medicine||Professional/Scientific Journal||Guest Editor||External||International||2020||2020|
The lab focuses on elucidating the molecular mechanisms of innate immune signaling, especially signal transduction pathways of pyroptosis and inflammation using multi-disciplinary approaches including cryo-electron microscopy (Cryo-EM) and X-ray crystallography. The lab also studies the host-pathogen interactions by elucidating the mechanisms how pore-forming proteins/toxins recognize the specific receptors, such as sugars, lipids, and proteins on the membrane of the target cells and mediate cell death. The study will allow us to develop new therapeutic strategies against inflammasome related diseases and microbial infections. The following list shows the representative recent projects.
Non-canonical inflammasome signaling
In the non-canonical inflammasomes, caspases, such as caspase-11 in mouse and -4/5 in human, recognize and are activated by cytosolic lipopolysaccharide (LPS) of Gram-negative bacteria, resulting in pyroptotic cell death. Besides LPS, caspase-11 is also activated by endogenous damage-associated molecular patterns, such as oxPAPC, an LPS mimic molecule generated by the oxidation of plasma membrane phospholipids during infections and tissue damage. We are interested in addressing the mechanisms how these caspases recognize signals and assemble into high-order complexes.
Gasdermin (GSDM)-mediated programmed cell death
GSDMs, especially GSDMD, are recently identified protein executioners of pyroptosis, a highly inflammatory form of programmed cell death triggered by the activation of inflammasomes. GSDMs are expressed predominantly in the gastrointestinal tract, skin, and immune cells and is implicated in a variety of inflammatory diseases and cancers. In our previous study, we have shown that the GSDMD N-terminal (GSDM-NT) fragments specifically bind acidic lipids and translocate on the membrane to form membrane-embedded pores upon cleavage by inflammatory caspases. Our cryo-EM structures of mouse GSDMA3 membrane pores identified a putative lipid-binding pocket and provided molecular details of oligomerization. However, more details in pore formation remain to be addressed, these include how lipid-binding triggers the oligomerization of GSDM-NTs and how oligomerization triggers the membrane insertion. Meanwhile, we are also interested in investigating the biological functions of other GSDMs.
Pore Forming Proteins/Toxins
The cell membrane provides an essential barrier from its external surroundings and creates a unique chemical environment for cellular processes. Pore-forming proteins/toxins (PFPs/PFTs) belong to an ancient protein family that exploited by both hosts and pathogens to rupture membranes and lyse target cells. Our lab will be elucidating the pore formation mechanisms of those PFPs using cryo-EM in combination with X-ray crystallography and other biophysics and biochemical methods.
The Lab is currently recruiting highly motivated post-doctoral research fellows. Interested persons please submit a cover letter, curriculum vitae, and a list of 3 references to Dr. Jianbin Ruan via email@example.com.
Accepting Lab Rotation Students: Summer 2022, Fall 2022, and Spring 2023
Nexinhib20 Inhibits Neutrophil Adhesion and β2 Integrin Activation by Antagonizing Rac-1-Guanosine 5'-Triphosphate Interaction.
Journal of immunology (Baltimore, Md. : 1950) 2022 Oct;209(8):1574-1585
Emerging enterococcus pore-forming toxins with MHC/HLA-I as receptors.
Cell 2022 Mar;185(7):1157-1171.e22
Gasdermin D pore structure reveals preferential release of mature interleukin-1.
Nature 2021 Apr;
Intracellular immune sensing promotes inflammation via gasdermin D-driven release of a lectin alarmin.
Nature immunology 2021 Feb;22(2):154-165
Mechanism of filament formation in UPA-promoted CARD8 and NLRP1 inflammasomes.
Nature communications 2021 Jan;12(1):189
Shiga toxin suppresses noncanonical inflammasome responses to cytosolic LPS
Science Immunology 2020 Nov;
FDA-approved disulfiram inhibits pyroptosis by blocking gasdermin D pore formation.
Nature immunology 2020 May;
SERPINB1-mediated checkpoint of inflammatory caspase activation.
Nature immunology 2019 Mar;20(3):276-287
Molecular mechanism for NLRP6 inflammasome assembly and activation.
Proceedings of the National Academy of Sciences of the United States of America 2019 Feb;116(6):2052-2057
Cryo-EM structures of ASC and NLRC4 CARD filaments reveal a unified mechanism of nucleation and activation of caspase-1.
Proceedings of the National Academy of Sciences of the United States of America 2018 Oct;115(43):10845-10852
Cryo-EM structure of the gasdermin A3 membrane pore.
Nature 2018 May;557(7703):62-67
Ubiquitin-Mediated Regulation of RIPK1 Kinase Activity Independent of IKK and MK2.
Molecular cell 2018 Feb;69(4):566-580.e5
The Pore-Forming Protein Gasdermin D Regulates Interleukin-1 Secretion from Living Macrophages.
Immunity 2018 Jan;48(1):35-44.e6
Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores.
Nature 2016 Jul;535(7610):153-8
An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells.
Science (New York, N.Y.) 2016 Jun;352(6290):1232-6
A single domain antibody fragment that recognizes the adaptor ASC defines the role of ASC domains in inflammasome assembly.
The Journal of experimental medicine 2016 May;213(5):771-90
Cryo-EM structure of the activated NAIP2-NLRC4 inflammasome reveals nucleated polymerization.
Science (New York, N.Y.) 2015 Oct;350(6259):404-9
Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes.
Cell 2014 Mar;156(6):1193-1206
Structural analysis of Shu proteins reveals a DNA binding role essential for resisting damage.
The Journal of biological chemistry 2012 Jun;287(24):20231-9
Targeted delivery of PLK1-siRNA by ScFv suppresses Her2+ breast cancer growth and metastasis.
Science translational medicine 2012 Apr;4(130):130ra48
Crystal structures of the coil 2B fragment and the globular tail domain of human lamin B1.
FEBS letters 2012 Feb;586(4):314-8
Structural basis of the chromodomain of Cbx3 bound to methylated peptides from histone h1 and G9a.
PloS one 2012 Jan;7(4):e35376
Sgf29 binds histone H3K4me2/3 and is required for SAGA complex recruitment and histone H3 acetylation.
The EMBO journal 2011 Jun;30(14):2829-42
Structural basis for specific binding of human MPP8 chromodomain to histone H3 methylated at lysine 9.
PloS one 2011 Jan;6(10):e25104
Cloning, purification, crystallization and preliminary crystallographic analysis of the tandem tudor domain of Sgf29 from Saccharomyces cerevisiae.
Acta crystallographica. Section F, Structural biology and crystallization communications 2010 Aug;66(Pt 8):902-4
Cloning, purification, crystallization and preliminary crystallographic analysis of a ribokinase from Staphylococcus aureus.
Acta crystallographica. Section F, Structural biology and crystallization communications 2009 Jun;65(Pt 6):574-6
Plasticity in PYD assembly revealed by cryo-EM structure of the PYD filament of AIM2.
Cell discovery 1
Monitoring gasdermin pore formation in vitro.
Methods in enzymology 2019 Jan;95-107
Structural Insight of Gasdermin Family Driving Pyroptotic Cell Death.
Advances in experimental medicine and biology 2019 Jan;
Mechanistic Insights into Gasdermin Pore Formation and Regulation in Pyroptosis.
Journal of molecular biology 2021 Oct;167297