Targeting a timer-integrator of cell checkpoint signaling for mesothelioma therapy

Our objective is to explore whether the prolongation to the BUB1 timer can be used to sensitize mesotheliomas to prevailing combinations of DNA-damaging and anti-mitotic therapies. For this purpose, we will first compare the properties of the BUB1 timer in engineered mesothelial and mesothelioma cell lines. We will proceed to explore BUB1-timer prolonging strategies using temperuture-based protocols or inhibators of timer silencing identified through screening of small-molecule libraries. The therapeutic efficacy of timer-prolonging strategies will be tested in cells and mousemodels of mesothelioma.