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.
We work closely together with the lab of Prof. Dr. Johannes Backs , especially on projects that relate to the RBM20 splicing target CAMK2D. Prof. Backs is a world renowned expert on CAMK2D- and HDAC4 signaling, and was Dr. van den Hoogenhof's postdoctoral mentor. Prof. Backs is the director of the Institute of Experimental Cardiology, in which the van den Hoogenhof lab is embedded.
We work closely together with the lab(s) of Prof. Dr. Lars Steinmetz. Prof. Steinmetz and Dr. van den Hoogenhof have a longstanding collaboration on studying the molecular mechanisms underlying RBM20 cardiomyopathy. Prof. Steinmetz heads a lab at Stanford (USA) and at the EMBL in Heidelberg.