Periodic Reporting for period 3 - iPROTECTION (Molecular mechanisms of induced protection against sepsis by DNA damage responses)
Reporting period: 2018-10-01 to 2020-03-31
The central goal of the current proposal is to identify and characterize novel cytoprotective mechanisms, with a focus on DNA damage response dependent protection activated by anthracyclines (the most commonly used chemotherapeutic drugs to treat cancer) as a window into stress-induced genetic programs conferring disease tolerance.
So far, we found important new cues into the molecular mechanisms of disease tolerance induction by DNA damage responses. Our main and most advanced results relate to the precise identification of the molecular mechanism by which anthracyclines specifically block the transcription of NFkB targets, when used at concentration below cytotoxic levels. In the course of this investigation, we also found that low levels of DNA damage promote survival against TNF-induced cell death, in an NFkB-independent manner. We are currently preparing a manuscript to report on our findings, while performing key experiments to more conclusively show the impact and relevance of our findings.