Investigating immune regulatory mechanism at the molecular, translational and clinical level
To discover disease mechanisms, we use chromatin immunoprecipitation followed by sequencing (ChIP-seq) to find active (i.e. open) gene regulatory elements (GRE) on a genome wide scale. Active GREs are genomic locations such as promoters and enhancers that contain transcription factors which in turn mediate the gene expression program in the cell. GREs are surrounded by a specific histone modification, histone H3 acetylated on lysine 27 (H3K27ac). H3K27ac ChIP-seq therefore provides a map of all active enhancers and promoters (regulome map) in any given cell type and under any condition.
Figure 1. Comparative epigenetic analysis
Regulome maps provide a snapshot of the genome-wide epigenetic state in any cellular condition. Depicted in the red box is an H3K27ac promoter peak that is present in the phenotype (e.g. disease, development state, drug treatment) but absent in the control condition. Bioinformatics analyses reveal s differential gene regulation, transcription factor activity or genetic variation that affects the regulatory region. This method can now be applied for disease-control population studies to discover disease relevant epigenetic changes.
We are building up three overlapping research areas which are part of the general scheme of immune-epigenetic regulation.
The first research area is to understand the fundamental mechanisms of how the immune system is regulated by epigenetics. Everyone is shaped by his unique genetic background and his unique environmental exposure. Together, they converge to a unique and personal epigenome which in turn causes a unique response to immune insults. We aim to better understand the underlying molecular mechanisms.
The second area of research aims to discover perturbations of immune regulatory mechanisms of diseases. The intention is to understand how the fundamental molecular mechanisms of immune regulation are disturbed in disease.
The third area of research aims to convert discoveries into clinical applications. The goal is to use the newly acquired knowledge from fundamental and disease mechanisms discovered in aim one and two and apply them to improve diagnostics and treatment outcome.