Oncogene-driven inflammasome activity in myeloid neoplasms and its impact on leukaemia development and anti-cancer immunity

Project Summary

We will study the myeloid cell-intrinsic impact of oncogene signalling on NLRP3 inflammasome activity and its consequences within and beyond the transformed cell. We will first systematically map the ability of relevant oncogenes to promote NLRP3 activation in vitro. For selected oncogenes, we will then use genetic tools to evaluate the impact of inflammasome signalling on disease progression and anti-cancer immunity in vivo and elucidate the mechanisms involved. The applicability of our findings will then be tested in patient samples. Overall, we aim to identify oncogenes for which modulation of inflammasome activity can be therapeutically beneficial, which we will finally attempt using our proprietary compounds.