Human Genetics 4 - Functional Genomics of Systemic Disorders

Principle Investigators
Prof.dr. Ko A.P. Willems van Dijk, prof.dr. Dorien J.M. Peters, Dr. Peter Hohenstein, Dr. M.E.T. Dollé (RIVM)

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 signalling and bioinformatics, pathogenesis, organoid culturing, drug screening and preclinical testing.

Based on a strong background in monogenic extremes of systemic disorders (including ApoE3-Leiden mutations in familial hyperlipidemia and PKD1 and PKD2 mutations in polycystic kidney disease), this program also aims to utilise the knowledge gained from these monogenic disorders in our studies to common and multifactorial forms.

Therefore, complex 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; PKD-DIPAK-consortium; PKD-Modifier consortium, Mayo-clinic). In addition, targeted analyses as well as high-throughput drug screening using organoids 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 antibody effector pathways in chronic inflammation in immune diseases. These are also important in autoimmune diseases such as arthritis and SLE. Advanced novel mouse models have been and are being generated for functional analysis of FcR and complement.

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LUMC Research Profiles : Vascular and Regenerative Medicine; Ageing; Biomedical Imaging