Dr. A. Yaël Nossent
MicroRNAs are small noncoding RNAs that bind to the 3’UTR of mRNAs and repress translation. The effect of a microRNA on a single mRNA/protein is small, but because microRNAs have many targets, often several hundred mRNAs, the biological effect of a single microRNA is very large. Besides microRNAs, several other types of small noncoding RNAs, including transfer RNAs (tRNAs) and small nucleolar RNAs (snoRNAs) can play a regulatory role in the cells of our bodies. Yaël studies how these tiny molecules influence the function of our blood vessels, both during health and disease.
Importantly, Yaël’s group found that a particular gene locus, 14q32, that encodes 3 long noncoding RNA, 41 snoRNA and 54 microRNA genes, plays crucial role in vascular remodelling, both in positive remodelling like angiogenesis and arteriogenesis, but also in negative remodelling like aneurysm formation, atherosclerosis and restenosis (Nossent et al, Ann Surg, 2013). Inhibition of individual 14q32 microRNAs led to enhanced blood flow recovery after ischemia (Welten et al, Circ Res, 2014). Simultaneously, inhibition of the same microRNAs led to a decrease in atherosclerosis (Wezel et al, Ann Surg, 2015) and restenosis (Welten et al, Atherosclerosis, 2017) and increased plaque stability (van Ingen et al, Mol Ther Nucleic Acids, 2019).
Small noncoding RNAs are important regulators of gene expression, but they themselves are subject to regulation as well. Yaël’s group has identified several RNA binding proteins that directly regulate the expression of 14q32 noncoding microRNAs during ischemia (Downie Ruiz Velasco et al, Mol Ther Nucleic Acids, 2019). Moreover, they identified several modifications these microRNAs undergo during ischemia (van der Kwast et al, Circ Res, 2018). RNA modifications are an important additional layer of regulation that can either (de-)stabilise an RNA, or even change its function. Yaël’s group found that 14q32 microRNAs are ‘edited’ under ischemia, causing them to shift their target gene set and induce angiogenesis only during ischemia (van der Kwast et al, Mol Ther Nucleic Acids, 2020).
Finally, Yaël focuses on small noncoding RNAs that are present in our blood. RNA can be released into the blood upon stress or injury, and as these RNAs are often very specific to the tissue that they came from, they are excellent biomarkers for many different diseases. Recently, Yaël’s group identified a set of tRNA-derived RNA fragments (tRFs) that allow us to distinguish between patient with acute ischemic stroke, haemorrhagic stroke and stroke mimics (stroke-like symptoms with a different cause) with high specificity and sensitivity (Nguyen et al, Int J Mol Sci, 2020). In collaboration with Delft University of Technology in the Netherlands, she is developing a chip-like device to detect these tRNAs in a drop of blood, to enable paramedics to make an accurate diagnosis of acute stroke, already in the ambulance.
Yaël Nossent is a molecular biologist with a particular interest in the role of noncoding RNAs in the vasculature. She obtained her Master degree in Biopharmaceutical Sciences from Leiden University in the Netherlands in 2002, after which she started her PhD research at the Leiden University Medical Center. She successfully defended her PhD thesis on determinants of plasma levels of von Willebrand Factor and coagulation Factor VIII in February 2008.
She then moved to Denmark for a three-year postdoctoral fellowship at the University of Copenhagen and the University of Southern Demark in Odense in the lab of Prof. Dr. Søren Paludan Sheikh, where she started working on microRNAs. After she moved back to the Netherlands in 2010, she started her own line of research on microRNAs in vascular remodelling, under mentorship of Prof. Dr. Paul Quax. Her research has been supported by grants from, among others, the Netherlands Organisation for Scientific Research (NWO) and the Netherlands Heart Foundation.
In 2017, she moved to Vienna, Austria, for a period of 4 years, to work both in Leiden and in Austria on the role of small nucleolar RNAs and RNA modifications in vascular remodelling, together with Prof. Dr. Christoph Binder and Dr. Johann Wojta. There, she obtained a Lise Meitner grant from the Austrian Science Fund (FWF).