Profile of Division
Functional analyses
of tumor-relevant genes
Certain gene
products are overexpressed or mutated in tumors. This is
particularly important when the corresponding proteins are functionally
relevant or causative for tumorigenesis, tumor progession,
-angiogenesis, -metastasis and/or -resistance. The specific knockdown
via RNA interference (RNAi) offers an approach for the analysis and
elucidation of molecular functions and cellular consequences of these
gene products.
Development of
novel, oligonucleotide-based therapeutic strategies
The targeted molecular interference via gene knockdown may lead to
novel therapeutic strategies. The therapeutic potential of RNA
interference, however, is seriously hampered by issues mainly related
to the delivery of small RNA molecules, e.g., siRNAs or chemical
derivatives, especially upon their systemic injection.
We develop and employ polymer-based nanoparticles for the delivery of
therapeutic nucleic acids, in particular small RNA molecules like
siRNAs or microRNAs (miRNAs). This includes novel chemical polymer
modifications, which are tested in vitro and in preclinical mouse
models in vivo with regard to efficacy and biocompatibility. Beyond
RNAi-based knockdown strategies, this approach is extended towards the
therapeutic application or inhibition of miRNAs, and allows for the
analysis of how miRNAs affect the expression of tumor relevant genes
and how this can possibly be exploited therapeutically (e.g., miRNA
replacement therapy).
These nanoscale therapeutics (‘nanomedicines’) are
further
studied in mouse models, mainly for the therapy of solid tumors or
metastases by targeting different growth factors, receptors and
downstream signal transduction molecules. However, in the frame of
collaboration projects, their therapeutic use is also extended towards
other pathologies.
Drug analysis /
clinical pharmacokinetics / drug therapy consulting / clinical
toxicology of acute intoxication
A second core competence of our Division is based on our longstanding
expertise in the field of drug analysis in biological samples, clinical
pharmacokinetics, consulting in questions of drug therapy and in the
clinical toxicology of acute intoxication. On this basis, we also
address questions regarding drug safety in critical patient
populations.
Results from our own research regarding drug safety, unwanted side
effects and acute toxic effects are also implemented in the new
editions of our textbook „AkuteVergiftungen und
Arzneimittelüberdosierungen“, which has become a
standard
reference work in the field (so far, only available in German).
By analyzing the clinical pharmacokinetics of centrally acting drugs
like Methylphenidate, Modafinil, Sulpirid,
Citalopram, Escitalopramor, Atomoxetin, we also participate in
collaboration projects with clinical neuroscience groups at the
University of Cambridge.
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