My fundamental and translational research combines both wet-lab and computational biology approaches.
From 2017 I work within the framework of Circulatory Health Research Theme at the Department of Experimental Cardiology and at the Laboratory of Clinical Chemistry and Hematology (LKCH) at the University medical Center Utrecht, where I use various omics techniques to study atherosclerosis, heart failure, and platelet biology.
Combining the genomic and epigenomic datasets I have shown that genetic variants in non-coding elements in the human genome, such as regulatory regions, are likely involved in IBD. Next, we have used this information to identify novel candidate genes by studying chromatin interactions at loci that have been associated with IBD through GWASs. We have for the first time demonstrated that 4C-seq and other 3C-derived methods can be applied to candidate gene identification in diseases with a complex genetic background and complement the classical candidate gene identification approaches. We have applied the same principle in other complex diseases – chronic kidney disease and coronary artery disease and stroke.
We work on the development of organoid based model systems in very early onset IBD (VEOIBD), which allow to delineate the pathophysiology, perform drug screening a personalized care for pediatric IBD patients. With this aim, I am combining RNA sequencing, histology, barrier function and microbial stimulation data to identify specific signatures that are associated with primary epithelial defects in VEOIBD. Next, I work towards an understanding of the fundamental principles of the inflammatory response of intestinal epithelium. In my group, we have identified intestinal epithelial stem cell as a major contributor to the pro-inflammatory response.
