Renal epigenetics and hypoxic gene regulation

Medicine 4

Head of Department:
Prof. Dr. med. Mario Schiffer

Team AG Schödel

Team AG Schödel (f.l.t.r.): Johanna Protze, Stephanie Palffy, Stephanie Naas, Astrid Ebenau-Eggers, Victoria Lauer, Johannes Schödel
Human renal tissue HIF-1α
Human renal tissue HIF-2α
In situ hybridisation
Northern Blot

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.

„Next-Generation Sequencing“ of FAIRE, HIF-ChIP and RNA
 
Group leader
PD Dr. med. D.phil. Johannes Schödel
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Scientists
Dr. med. Steffen Grampp
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Dr. rer. nat. Victoria Lauer
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Dr. med. Stephanie Naas
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Technicians
Astrid Ebenau-Eggers
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Stephanie Palffy
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Graduate students

Johanna Protze
Carlotta Schönau