Toll-like receptor (TLR) signaling
BACKGROUND
TLRs represent a family of receptors essential for recognizing pathogens. They initiate signaling via adaptor proteins and partially defined pathways. TLRs upregulate inflammatory genes to initiate immune responses, however, exaggerated/ prolonged TLR activation can lead to inflammatory pathology.
OUR MAJOR OBSERVATIONS
We identified/ characterized various components of these pathways, including MyD88 and TRAF6 as part of the TLR9 pathway (recognizing DNA), TRAF3 as regulator of interferons and IL-10, and ABIN1/TNIP1 as regulator of the C/EBPb pathway.
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PROJECT LAYOUT
We use primarily artificial dimerization of adaptor proteins and affinity purification to characterize transiently assembled signaling complexes by quantitative mass spectrometry. We characterize identified proteins functionally in vitro and in vivo.
CURRENT FOCUS
We explore the molecular mechanism of TNIP1 function, which is essential to protect us from inflammatory diseases. We also work on a new ‘signaling protein, which controls the transcription factor family‚ interferon regulatory factors (IRF).
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KEY PUBLICATIONS
Haecker, Nature 2006 (PMID: 16306937)
Zhou, PNAS, 2011 (PMID: 22011580)