P6: targeting trained immunity
Trained immunity in cardiac cells
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Immune activation and inflammation characterizes repAMI. DAMPs can induce trained immunity in some non-immune cells through epigenetic, transcriptional and metabolic reprogramming. This primes cells for a stronger response to subsequent inflammatory triggers. Simulated I/R evokes epigenetic modifications in vitro. Development of immune memory in cardiac cells in the setting of repAMI has not been reported.
To dissect the mechanisms and consequences of transcriptional, metabolic and epigenetic remodeling in cardiac cells in repAMI.
Specific objectives are:
- RepAMI-triggered immune training of cardiac cells and the impact on post-infarct inflammation and resolution
- Spatial and cellular context of immune remodeling
- Validation of druggable candidates in translational models
Principal Investigators