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Eric van der Veer, PhD

Research Spotlight
The modulation of cellular phenotype is intimately intertwined with organ function, repair upon injury and the pathophysiology of disease. The cardiovascular system possesses numerous cell types, such as vascular smooth muscle cells (VSMCs), endothelial cells (ECs), monocytes and macrophages and cardiomyocytes, that are conferred with the capacity to undergo phenotypic switches in response to acute or chronic injury that serve to limit tissue damage and restore proper cardiovascular function. However, these reparative cellular phenotypes can also drive the onset, persistence and exacerbation of cardiovascular disease. An example of this phenomenon is the pre-stenotic fibroproliferative response of medial VSMCs as a result of endothelial denudation of the coronary artery after percutaneous coronary interventions (PCI) or the differentiation of monocyte subsets into various highly plastic macrophage phenotypes profoundly impacts atherosclerotic lesion development and progression.

RNA-binding proteins (RBPs) are rapidly emerging as pivotal players in these alterations in cellular function, as coordinators of all aspects of (patho)physiological RNA processing and gene expression. In the past decade, extensive work has elucidated the sequence to which many of these RBPs bind, enabling one to identify putative RNA species specifically targeted by individual RBPs. Amongst the estimated 900 RNA-binding proteins, our focus is Quaking, a K-homology domain-containing protein that we have established is an essential post-transcriptional regulator of RNA fate in the cardiovascular setting. Quaking guides pre-mRNA splicing, transcript abundance and translation, as well as cellular localization.

This knowledge, when coupled with the recent development of sophisticated delivery methods for RNA-based therapeutics, provides the interesting possibility of modifying the transcriptome by altering RBP expression or activity, or targeting specific RBP-mediated events, making it possible to direct molecular pathways involved in disease pathogenesis.

Key publications
1. de Bruin, R.G., et al. Quaking promotes monocyte differentiation into pro-atherogenic macrophages by controlling pre-mRNA splicing and gene expression. Nature Communications, 2016.
2. van der Veer, E.P., et al. The RNA-binding protein Quaking is a critical regulator of vascular smooth muscle cell phenotype. Circulation Research, 2013.
3. de Bruin, R.G et al. Emerging roles for RNA-binding proteins as effectors and regulators of cardiovascular disease (Review). European Heart Journal, 2016.
4. de Bruin, R.G. et al. The RNA-binding protein Quaking maintains endothelial barrier function and affects VE-cadherin and beta-catenin function. Scientific Reports, 2016.
5. Hafez, S.Q. et al. Modeling the combined effect of RNA-binding proteins and microRNAs in post-transcriptional regulation. Nucleic Acids Research, 2016.
6. van der Veer, E.P. et al. Intrinsic directionality of migrating vascular smooth muscle cells is regulated by NAD+ biosynthesis. Journal of Cell Science, 2012.
7. van der Veer, E.P. et al. Extension of human cellular lifespan by nicotinamide phosphoribosyltransferase. Journal of Biological Chemistry, Accelerated Publication, 2007.
8. van der Veer, E.P., et al. Pre-B-cell colony-enhancing factor regulates NAD+-dependent protein deacetylase activity and promotes vascular smooth muscle cell maturation. Circulation Research, 2005.

Ongoing Quaking and RNA therapeutic research projects
Even when you think you have it all figured out, Mother Nature continues to throw curveballs that force you to reconsider what is known and what is unknown. Here below you can find a brief description of what we know, and gain an appreciation for the fact that there is still much to be discovered in our ‘Ongoing research projects’ section:

Current ‘Team QKI’ members
Juan Pablo Romero M.Sc. (visiting scientist)
Eva Argiro B.Sc. (Research Internship)
Hayat Suleiman B.Sc. (Research Internship)
Franca Witjas B.Sc. (Research Internship)

Previous ‘Team QKI’ members
Karima Hazzouti B.Sc. (Free University of Amsterdam Biomedical Sciences student – Research Internship)
Rick Sijbom M.Sc. (Volunteer Research Analyst)
Patrick van der Zande B.Sc. (Biomedical Sciences student – Research internship)
Wesley van der Weijden M.D. (Medicine student – Research internship)
Bernadetta Bandyga M.Sc. (Volunteer Research Analyst)
Merijn Doop M.Sc. (Biomedical Sciences student – Research Internship)

CV: CV Dr. Eric vd Veer