In the laboratory the focus is the identification of pathognomonic genetic changes in sarcomas using various technological platform and establish cell lines to facilitate further research in these rare tumour entities.
The major line in research topic is strongly associated with the translational aspect where results are utilized directly in clinical-pathological settings. Testing the clinical relevance of the pathognomonic genetic changes is necessary to introduce these findings as potential diagnostic tests and to (sub)classify diseases based on their genetics.
For the investigation and understanding of the underlying pathophysiology cell lines established from patient samples are inevitable. Establishing model systems to perform functional test and identify actionable target and drugs cell lines derived from rare tumor entities necessary.
Studying of naturally occurring, disease causing genetic variants (forward genetics) is an inevitable approach to identify disease causing changes when it is coupled to clinical settings. Natural selection of these variants will help understanding not only pathological conditions but could shed light on physiological roles of cellular processes. The use of these samples will allow me to take clinically relevant translational steps including participation of in a large network leading to access to access more patient samples.
As an example, we study the underlying mechanism of action how the MYOD1 c.365T>G, p.L122R mutation, escribed by us, leads to oncogenic transformation in spindle cell rhabdomyosarcoma. Molecular biology tool boxes and CRISPR/Cas gene editing in combination with by ChIP- and transcriptome next generation sequencing in combination with functional studies will enable us not only the understanding rhabdomyosarcoma genesis, but may also provide information on normal skeletal muscle differentiation and development.