Uncovering the Cell Biology of Innate Immune Receptors
We study how innate immune receptors function within the broader subcellular context and uncover pathways that safeguard against aberrant activation.
Projects
Lab Projects (4)
Endosome malfunctions and TLR-driven autoimmune disease
Dysregulated sorting of the RNA-sensor TLR7 can cause the autoimmune disease systemic lupus erythematosus (SLE). We recently discovered a new role for the BORC complex in directing TLR7 to degradation pathways, thereby controlling intracellular TLR7 levels and preventing self-reactivity to host-derived RNA. In this project we further explore how BORC contributes to immune homeostasis.
Environmental triggers of TLR self-reactivity
Gain-of-function mutations in TLR7 or its chaperone UNC93B1 can cause pediatric SLE. Besides genetic predispositions also environmental factors are involved in triggering or promoting autoimmune diseases. We are examining how external cues can sensitize TLR7 towards self-recognition.
Real-time visualization of TLR signaling
Endosomal TLR7 and TLR9 activate two major signaling pathways: 1) NFkB - inducing proinflammatory cytokines and 2) IRF - inducing type I interferons. These two signaling branches are thought to originate from distinct endosome subsets, however this bifurcation has not been directly visualized before. We are using super-resolution microcopy and custom reporter cell lines to track compartment-specific TLR signaling in real time.
Endosome biology and inflammasome regulation
Inflammasomes, such as NLRP3, are also regulated by subcellular organelles during their activation. We aim to define how endosome biology shapes inflammasome activation and downstream immune responses.
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