My expertise is in the field of “Molecular Basis of Genetic Diseases” and major scientific achievements include the identification and functional characterization of more than 30 novel kidney disease genes in patients with nephronophthisis, Joubert syndrome, Senior-Løken syndrome, nephrotic syndrome, primary ciliary dyskinesia, and karyomegalic interstitial nephritis. Scientific findings have been published in i.e. Nature Genetics (17), AJHG (15), JASN (13), Cell (2), NEJM (2), PNAS (2), and Nature (2).
Recently, I have implemented microfluidic droplet-based RNAseq technology (Drop-Seq) to analyze adult and fetal kidney tissue on the single-cell level. The technique is based on combining single-cells with barcoded beads in separate nanoliter-sized droplets in the course of flowing oil, beads, and cells through a droplet-generator device. This technique allowed us to establish single-cell gene expression signatures and further to define nephron cell type composition of human developing kidney tissue. Furthermore, we use scRNAseq to analyze single cells from cultured organoids derived from iPSC and hESC. The single cell RNA-Seq approach allows the detection of novel renal cell (sub)types, novel transcriptional pathways and biomarkers for diagnostics, renal disease progression, prognosis, and potential therapeutic interference.

My research focuses on the identification and functional characterization of novel mutated kidney disease genes in patients with recessive ciliopathies, dominant cystic diseases, or glomerular kidney diseases. Currently, we apply next-generation sequencing and bioinformatics to generate and analyze whole exome, genome and transcriptome data for hundreds of patients.
• I am also interested in technologies which allow high-throughput mutational analyses for large patient cohorts. Consequently, I have implemented microfluidic PCR-based Access Arrays and in collaboration with various groups worldwide we successfully performed high-throughput mutational screens for more than 3,000 patients with cystic kidney diseases, congenital kidney abnormalities, glomerular kidney diseases, or with congenital heart diseases.
• Another research goal is to establish an efficient in vitro system to functionally characterize variants of unknown significance (VUS) found in various inherited diseases. Therefore, we are generating kidney disease-gene specific human knockout cell lines by applying CRISPR-Cas9 genome editing techniques coupled with RNA-Seq and transcriptome profiling. Those cells will be crucial to establish inducible stable lines expressing respective VUS. We expect that the transcriptome signature will significantly differ after induced expression of a modified gene carrying a deleterious mutation compared to benign wildtype polymorphisms.
• Recently, I have implemented the novel microfluidic droplet-based technology (Drop-Seq) which allows to uniquely barcode mRNA transcripts of thousands of individual cells derived from a complex tissue for downstream RNA-Seq expression analyses. The technique is based on fusing single-cells with barcoded beads in separate nanodroplets in the course of flowing oil, beads, and single cells through a droplet generator device via 3 syringe infusion pumps. We are currently establishing transcriptomics on the single cell level and define detailed cell type composition and nephron segment origin of cells derived from healthy kidney tissue and from kidney biopsies of patients with glomerular and other kidney diseases. We expect to identify new renal cell (sub)types and states and we will compare RNA expression patterns with formerly established specific renal transcriptome datasets. This project may help to identify new cell type specific biomarkers for diagnostics, disease progression prediction, and for potential therapeutic interference.