Chen Shen
Washington University in St Louis, MO·Biophysics
Cells carry internal alarm systems that detect signs of infection and trigger inflammation. Among them are inflammasomes: multi-protein assemblies that switch on inflammatory enzymes called caspases and can drive an infected cell to die in a way that alerts the immune system.
- Fields
Biophysics
Microbiology & Immunology
Biochemistry
- Topics
inflammasome
Gag
matrix protein
- Grants
- 2 known grants, through Jul 2030
What they work on
- Characterize functionally how HIV-1 Gag and its matrix (MA) region bind the CARD8 inflammasome sensor to prevent its activation by the viral protease, and compare the strength of this inhibition across matrix proteins from different HIV-1 subtypes.
- Determine the atomic-level structure and biochemistry of Gag- and matrix-mediated CARD8 sequestration, to explain why this interaction reduces the ability of non-nucleoside reverse transcriptase inhibitors to clear HIV-infected cells.
- Solve cryo-electron microscopy structures of bat NLRP6 alone and bound to viral double-stranded RNA, and map the biochemical basis of that RNA interaction.
- Compare the structural mechanisms of double-stranded RNA sensing and inflammasome signaling among bat, mouse and human NLRP6 to identify features unique to bats.
- Test RNA virus-induced bat NLRP6 inflammasome signaling in reconstituted intestinal epithelial cells and in Eonycteris spelaea cells exposed to bat-borne RNA viruses.
- Define the genetic role of bat NLRP6 in inflammasome signaling using primary bat intestinal epithelial cells and bat intestinal organoids.
More about the research
Two projects here use structural biology to work out how specific inflammasome sensors read viral cues — one in human cells infected with HIV, one in bats, animals that carry lethal viruses without getting sick. Both ask the same underlying question: what exactly does the sensor touch, and how can that interaction be redirected for therapy?
Why it matters
Mapping how HIV's Gag protein disables CARD8 could guide drugs that free this sensor to kill infected cells, a strategy aimed at the viral protease activity HIV cannot mutate away and therefore relevant to HIV cure efforts. Separately, learning how bat NLRP6 senses viral RNA without causing damaging inflammation could inform therapies for gastrointestinal inflammatory and autoinflammatory disorders in people.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Penghua Wang
University of Connecticut, CT·Microbiology & Immunology
Test whether unanchored lysine 48- and lysine 63-linked ubiquitin chains bind caspase-4/11 and promote its assembly and activation, using cell-free and biochemical assays.
Wei Li
University of Pittsburgh, PA·Microbiology & Immunology
Engineer soluble CD4 D1-domain variants with improved binding kinetics and isolate single-domain VH binders against CD4-induced epitopes on HIV envelope, combining computational structure design, phage display and time-resolved cryo-electron microscopy.
Emily Troemel
University of California-San Diego, CA·Microbiology & Immunology
Determine where and how the RIG-I-like receptor DRH-1 promotes defense against Orsay virus in C. elegans intestinal epithelial cells, including how it senses viral replication and triggers the IPR.
The school
Washington University in St Louis: 97 labs on PI Pages, $1.2B a year on research, 365 research doctorates a year.
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