The NO/cGMP signaling cascade regulates a broad spectrum of biologic processes. Using gene targeting in embryonic stem cells and RNAi (see below), we analyze the function of cGMP-regulated proteins, such as cGMP-dependent kinases und ion channels in vitro and in vivo. The main focus is on the cGMP signaling pathway in white and brown adipose tissue as well as in metabolically important organs.
Viral Vectors & RNAi
Our goal is to combine modern virology and transgenic technologies. We focus on retroviral and lentiviral vectors. Lentiviral vectors are a promising tool for molecular biology and gene therapy. Lentivectors can efficiently transduce non-dividing cell like neurons, hepatocytes and muscle cells in vitro and in vivo. In addition, these vectors can be used for gene transfer in stem cells including embryonic stem (ES) cells. We and others have established the use of lentiviral vectors for the generation of transgenic animals (lentiviral transgenesis). Transduction of preimplantation embryos with lentiviral vectors results in the expression of the lentivirally delivered transgene during embryonic development as well as in the newborn and adult animal. Lentiviral transgenesis has been established for a broad range of species including mice, rats, pigs, cattle and chicken.
RNAi (RNA interference) is a potent tool to suppress specific genes in human cells and has great potential for therapeutic use in many disorders. Exogenously produced siRNA molecules can be directly used to silence cellular gene expression. However, this requires chemical or enzymatic synthesis as well as efficient RNA transfer to the target cells (e.g. by RNA transfection, electroporation). An alternative approach is to produce siRNA (small interfering RNAs) within the target cell from RNA polymerase III (PolIII) transcription units. Presently, the most wide-spread siRNA/shRNA expression cassettes contain either the promoter of the RNAse P RNA H1 or small nuclear RNA U6. Transfer of these expression cassettes into cells can be efficiently achieved by viral vectors in vitro and in vivo. Our laboratory focuses on the development of RNAi-based approaches for the treatment of neurodegenerative disorders.
Drug delivery & Nanomedicine
Our aim is the development of nanomedicine-based strategies for targeted delivery of innovative therapies, i.e. genetic material (nucleic acids and viral vectors), as well as genetically modified cells (especially stem and progenitor cells) in the cardiovascular and the central nervous system.
Institut für Pharmakologie und Toxikologie/Biomedizinisches Zentrum
Forschung & Lehre