Human Genetics

Characterization of pathogenic processes

A major goal of our research is to understand the pathogenic processes underlying diseases. We frequently identify pathogenic variants in disease-associated or novel candidate genes. Subsequently, the biological function of disease genes is characterized in our laboratory to better understand the relevance of mutations for diseases. We make use of patient-derived cells (skin biopsy-derived fibroblasts) to identify disease-relevant mechanisms. Examples of techniques applied to study the consequence of mutations include DNA/RNA/protein analyses, different cell culture techniques, and immunohistochemical stainings.


The cilium is a protrusion from the cell surface that functions as a signaling antenna and regulates biological pathways. The photoreceptors of the retina contain a specialized cilium, the so called connecting cilium. Indeed, retinal degenerations are frequently caused by mutations in genes that affect the function and properties of the cilium. Mutations in ciliopathy-associated genes can cause non-syndromic or syndromic forms of diseases with a wide range of phenotypes. Examples of ciliopathies include Retinitis Pigmentosa, Leber´s congenital amaurosis, or Bartet Biedl syndrome.

We study the correlation between retinal diseases and ciliary properties. For this purpose, the generation of cilia can be induced in cell culture to measure ciliary length and frequency. Applying several different ciliary assays, we found that many mutations in disease genes belong to the group of ciliopathies. Among those disease genes is RPGR, which is likely to cause retinal degenerations by a mislocalization of its protein along the cilium. Furthermore, we successfully applied therapeutic strategies to treat the underlying genetic defect and corrected the ciliopathy phenotype in cultured cells.