Research interests

One of the most exciting and important recent scientific discoveries was that RNA interference (RNAi), a natural cellular mechanism of gene silencing triggered by small double-stranded RNAs, is active in mammals and humans. With its unique efficiency, simplicity and specificity, RNAi holds enormous promise as a functional research tool for genome annotation. Concurrently, RNAi represents a novel and utmost promising clinical modality for the treatment of human diseases with an underlying genetic cause, including viral infections and cancers. Accordingly, our two major goals are to unravel the fundamental principles of RNAi networks in higher organisms and to fully unlock the therapeutic potential of RNAi in humans. In our lab, we thus put an equal interdisciplinary focus on basic biological as well as on applied biomedical studies. In particular, we aim at delineating the physiological role and interplay of miRNAs and Argonaute proteins as main components of RNAi networks. In parallel, we explore potent avenues towards the clinical translation of RNAi, using cell culture and small animal models of human disease, esp. infection with HIV or Hepatitis viruses B or C. Specifically, we create synthetic gene therapy vectors based on genetically enhanced Adeno-associated viruses (AAV) that we engineer to mediate targeted stable RNAi. In the past, we have already reported their potential to permanently and safely suppress HBV in adult mice, and we now further expand our vector system for the therapeutic expression or inhibition of miRNAs that are involved in HIV or HCV infection, Malaria and other human disorders. Last but not least, we profile and study circulating extra-cellular miRNAs as putative signal transducers and sensitive novel blood-borne biomarkers for human viral infections.

 

Methods applied

Our group utilizes a broad array of state-of-the-art molecular, cellular, virological and biochemical in vitro & in vivo assays. We also actively develop novel powerful custom techniques, such as high-throughput library strategies for protein/virus evolution and screening, or high-resolution, high-content RNAi microscopy platforms. Moreover, we collaborate with external experts in various hot areas, including zinc finger nuclease and stem cell technologies.