Other research focuses
Lehrstuhl für Biochemie und Molekulare Medizin
Furthermore, BMPs play a major role in many cancer diseases. In our studies we could show that activation of the BMP specific smad signaling cascade is involved in progression of hepatocellular carcinoma (HCC) (Maegdefrau et al., 2012 Exp Mol Pathol).
In current studies we investigate the function of BMPs in NAFLD (non-alcoholic fatty liver disease), because research on NASH (non-alcoholic steatohepatitis) mouse models and NAFLD patients showed an increased BMP6 expression in the damaged liver.
We were the first to show that the Fussel-15 expression is induced during early wound healing and capable of negative regulation of BMP signaling. Fussel-15 interacts directly with the Smad molecules and inhibits thereby the transcription of several target genes.
Keloid patients, who show excessive scarring and patients with localized scleroderma, who suffer from hardening of the connective tissue, show altered Fussel-15 expression and accordingly defective TGF-ß/BMP signaling.
In the course of our studies we try to clarify the molecular function of Fussel-15 and BMPs during normal wound healing and moreover during pathophysiological processes.
Here, we aim to define the role of Netrins and Slits and their receptors uncoordinated locomotion/Deleted in Colorectal Carcinoma (UNC/DCC) and roundabout (Robo) in inflammatory and degenerative alterations in the articular cartilage in rheumatoid arthritis (RA) and osteoarthritis (OA). Our studies suggest that deregulation of these molecules leads to a loss of defined tissue boundaries which promotes the progression of RA and OA. In order to indentify regulatory mechanisms of the repellent receptors the expression of miRNAs was determined. This showed a de-regulation of certain miRNAs, which regulate a variety of genes beside UNC and Robo, providing new possible targets for RA/OA therapy.
Characterization of the molecular mechanism how MIA/CD-RAP effects chondrocyte differentiation is one of the major goals in this project.
As well as MIA/CD-RAP the transcription factor AP-2ɛ participates in chondrocyte maturation. We could show that AP-2ɛ promotes differentiation of cartilage in late, hypertrophic stages. The next task is to analyze the specific function of the protein during endochondral ossification and which target genes are regulated by this transcription factor.
Additionally AP-2ε plays a role in osteoarthritis, a degenerative joint disorder, and is over-expressed in osteoarthritic cartilage. Therefore the function of AP-2ɛ in the context of this disease needs to be further investigated.
Our aim is to study the cellular mechanisms and molecular functions of plasma during wound repair and treatment of different tumors.