Kliniken &… Kliniken Zentrum für Innere… Innere Medizin VIII:… Groups RNA Splicing in Cardiac…

RNA Splicing in Cardiac Disease (van den Hoogenhof)

The van den Hoogenhof lab is a newly formed Junior Research Group at the Innovation Campus Region Rhein Neckar. The group is embedded in the Institute of Experimental Cardiology, which is a highly innovative and well-equipped institute, and part of the Heidelberg University Hospital. The van den Hoogenhof lab studies RNA splicing processes as well as the functional effects of missplicing and splice variants in the heart. 

One of the most exciting advances in the last decades is that of next-generation sequencing technologies, which has led to a much greater understanding of the extent of RNA splicing. In the 1980s, it was thought that about 5% of human genes were subjected to alternative splicing. Now, this number has risen to >95%, meaning that the vast majority of mRNAs are subjected to alternative splicing. Consequently, most protein-coding genes encode for multiple proteins with (slightly) different or even opposing functions. Studies on pivotal cardiac splicing factors have shown the importance and functional relevance of splicing in the heart. For example, mutations in the splicing factor RBM20 lead to an arrhythmogenic dilated cardiomyopathy, and a single SF3B1-coordinated switch in Ketohexokinase isoforms is sufficient to actuate cardiac fructose metabolism and drive cardiac dysfunction. These recent findings put RNA splicing on the map as an important additional regulator of cardiac function, and with our research, we aim to further unravel the splicing code in the heart.

Currently, the group focuses on 3 main topics; 

1) the molecular mechanisms underlying RBM20 cardiomyopathy, 

2) the role of minor splicing in the heart, and 

3) the identification and characterization of novel (master) splicing regulators in the heart. 

The lab works closely together with labs around the world, including the lab of Prof. Johannes Backs (Heidelberg, Germany) and Prof. Lars Steinmetz (Stanford, USA/Heidelberg, Germany).