Our laboratory is interested in cardiac gene regulatory mechanisms by transcription factors and microRNAs that control pathological cardiac remodeling, an early step towards heart failure. Chronic heart failure is a progressive disorder of the heart muscle that affects all vital organs, ultimately resulting in loss in quality of life. The most important causes of heart failure are chronic hypertension and myocardial infarction.
We study all three major cell types of the heart: cardiac muscle cells, fibroblasts and endothelial cells which express distinct sets of genes controlled by different combinations of extracellular signals, transcription factors and non-coding RNA species. We study these models to understand how programs of cellular differentiation and morphogenesis are affected in the processes leading to severe heart disease.
We focus on discovering new transcription factors that control these cell types in response to cardiovascular diseases. Our studies aim to decipher the precise workings of the transcription factor Nuclear Factor of Activated T-cells (NFAT), in the reprogramming of cardiac gene expression, and the discovery of novel partners of this transcription factor family.
More recently, our laboratory has gained interest in microRNAs (miRNAs), a class of endogenous, small, noncoding RNAs, which suppress protein expression by either messenger RNA degradation or translational inhibition. Each miRNA potentially targets multiple transcripts, suggesting that miRNAs, not unlike transcription factors, have a fundamental role in regulating gene expression.
The processes we study are evolutionarily conserved across diverse organisms. This conservation allows us to take a cross-species approach to dissect the precise workings of single genes in simple cellular systems, perform gain and loss-of-function experiments in vivo using mouse models of disease and study the relevance of disease mechanisms in human heart disease. Our goal is to dissect genetic pathways for the function of each cardiac cell type and to use this information to devise pharmacologic and genetic therapies for inherited and acquired diseases in humans.
Our laboratory integrates the use of routine molecular and cell biological approaches, high-throughput genetic screening facilities, transgenesis/gene knock-out technology, physiological cardiac phenotyping and non-invasive imaging techniques. Our laboratory is made up of an international team of students and postdoctoral fellows and is located at the Department of Cardiology, CARIM School for Cardiovascular Diseases, Maastricht University. Many alumni from our group have successfully started their own research laboratories, fulfill executive industrial functions or became clinician-researchers as the next generation of leaders in (cardiovascular) medicine.