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Renal epigenetics and hypoxic gene regulation

Hypoxia plays an important role in many physiologic and pathophysiologic processes. Hypoxia-inducible transcription factors (HIF) are central to hypoxic gene regulation. By binding DNA at hypoxia responsive elements HIFs activate transcription of genes such as erythropoietin, VEGFA, Cyclin D1 and glycolytic enzymes that regulate adaptive processes in the cell and the whole organism.

HIFs can activate protective mechanisms which lead to a better tubular function in acute kidney injury. In contrast, in VHL-associated renal cancer permanent activation of HIFs can contribute to disease progression.

We aim to identify cell type specific functions and epigenetic characteristics of HIF-DNA binding as well as mechanisms that directly influence HIF-DNA interactions. We use modern technologies to identify HIF-binding sites and analyse protein-DNA interactions (Next generation sequencing: ChIP-seq, FAIRE-seq, RNA-seq). We evaluate the transactivation potential of these sites by genome-editing (CRISPR/Cas, TALEN) in relevant cell lines. Furthermore, we explore interactions of HIF-binding, epigenetics and single nucleotide polymorphisms in the context of renal cancer and acute and chronic kidney disease.

Team AG Schödel

Graduate students

Rene Krüger (Focus on glomerulus)
Johannes Weidt (Focus on tubulointerstitium)