Photo of Jianbin  Ruan, Ph.D.

Jianbin Ruan, Ph.D.

Assistant Professor of Immunology
Academic Office Location:
Immunology
UConn Health
263 Farmington Avenue
Farmington, CT 06030-1319
Website(s):

Department of Immunology

Education
DegreeInstitutionMajor
B.S.University of Science and Technology of ChinaBiotechnology
Ph.D.University of Science and Technology of ChinaStructural Biology

Post-Graduate Training
TrainingInstitutionSpecialty
FellowshipHarvard Medical School, Boston Children's HospitalResearch

Awards
Name of Award/HonorAwarding 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 & DescriptionCategoryRoleTypeScopeStart YearEnd Year
Molecular Aspects of MedicineProfessional/Scientific JournalGuest EditorExternalInternational20202020

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 ruan@uchc.edu.

Accepting Lab Rotation Students: Summer 2022, Fall 2022, and Spring 2023

Journal Articles

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