Human Genetics 4 - Functional Genomics of Systemic Disorders
Aim and focus
The common focus of this program is to apply functional in vitro, in vivo as well as genome wide studies to uncover and resolve the mechanisms underlying systemic disorders such as metabolic syndrome, type 2 diabetes, cardiovascular disease and kidney failure. The aim of this multidisciplinary, state-of-the art program is to understand and to translate the insights gained into mechanisms and pathophysiology of these (complex multifactorial) diseases towards the development of improved prediction, prevention, new drug targets and potential therapies. Therefore, our research covers a broad range of topics such as genotype-phenotype studies, modifying genes, studies on expression and functions of the genes/proteins involved, cellular signaling and bioinformatics, pathogenesis, organoid culturing, drug screening and preclinical testing.
In addition, gene-gene and gene-environment interactions are investigated using the full spectrum of genome wide technologies and mathematical systems biology approaches on prospective epidemiological cohorts that are available in-house (Netherlands Epidemiology of Obesity study) or in close collaboration (Doetinchem study, RIVM; Erasmus Rucphen Family Study, Erasmus University Rotterdam; Polycystic Kidney Disease (PKD) DIPAK-consortium; PKD-Modifier consortium, Mayo-clinic).
In addition, targeted analyses as well as high-throughput drug screening using more complex in vitro models are among the approaches to identify potential therapeutic targets. These are multidisciplinary programs in collaboration with bioinformaticians, chemo-informaticians, clinicians and toxicologists. One of the common mechanisms studied, involves the impact of environmental stressors such as inflammation or metabolic stress on the expression of disease. We also study the link between normal kidney development and kidney diseases, such as Wilms’ tumours and Congenital Anomalies of the Kidneys and Urinary Tract (CAKUT). An important focus point here is the integrated single cell transcriptomic and epigenomic analysis of control and mutant embryonic mouse kidney samples to understand the primary effects of mutations that lead to these diseases. These data will profit from ongoing analyses of PKD models and vice versa provide new developmental insights that will improve our understanding of the origins of that disease as well.