Lezing 'Targeting ER-resident proteins in B cells has a 'sting' in its tail'

Voor wie
Medewerkers, Alumni, Bedrijven
15-09-2017 van 11:30 tot 12:45
UGent-VIB-onderzoeksgebouw, Technologiepark 927, 9052 Zwijnaarde
Door wie
VIB-UGent Center for Inflammation Research (GE01/WE14/WE10)
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Chih-Chi Andrew Hu from the Wistar Institute, Philadelphia, USA will present his recent work on ER stress in leukemia.

The IRE-1/XBP-1 pathway is the most conserved endoplasmic reticulum stress response. We discovered that genetic deletion of XBP-1 significantly decelerates the progression of chronic lymphocytic leukemia (CLL) in mice. We designed a specific inhibitor, B-I09, which blocks the IRE-1/XBP-1 pathway with high potency and efficacy. B-I09 specifically targets mouse CLL cells in vivo by inducing apoptosis. B-I09 may help FDA-approved ibrutinib achieve higher cytotoxicity in CLL cells at a lower dose, addressing ibrutinib’s toxicity issue. IRE-1 interacts with another ER-resident protein called STING. STING is critical for cytoplasmic DNA sensing and interferon production. We showed that the IRE-1/XBP-1 pathway is required for the interferon-producing function of STING. In CLL-bearing mice, injection of a STING agonist induced apoptosis and regression of leukemia. These data suggested that IRE-1 and STING are both useful ER-resident protein targets for the treatment of B cell cancer.