Emmy Noether Junior Research Group Precision Sarcoma Research
Dr. Priya Chudasama
Prospectively collected and clinically annotated primary human sarcoma specimens are characterized by employing state-of-the-art technologies, followed by investigation into the functional and mechanistic consequences of selected alterations. Potentially “actionable” targets are be taken forward to investigator-initiated clinical trials of biology-guided sarcoma treatments.
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Sarcomas are rare and aggressive mesenchymal malignancies of the connective tissues, which include fat, blood vessels, nerves, bone, muscles, deep skin tissues and cartilage. Sarcomas are mainly divided into two types, bone sarcoma and soft-tissue sarcoma. Sarcomas display remarkable genetic and histologic diversity, as reflected by more than 150 subtypes according to the World Health Organization Classification, which in turn poses significant diagnostic and therapeutic difficulties. “Actionable” lesions that allow prediction of response to conventional or targeted anti-cancer drugs and/or represent direct targets for therapeutic intervention are lacking in the majority of cases due to incomplete understanding of the events that drive sarcoma development.
The Precision Sarcoma Research group funded by the Emmy Noether Program of the German Research Foundation (DFG) has been established with the aim to better understand the molecular alterations underlying tumor development and to identify novel targets for precision cancer therapy. To this end, we employ tumor multi-omics data generated within the in-house precision oncology workflows, in particular the NCT/German Cancer Consortium (DKTK) MASTER (Molecularly Aided Stratification for Tumor Eradication) as well as publicly available data resources to systematically investigate the genomic, epigenomic, transcriptomic and immunologic landscapes of sarcomas to identify pan-sarcoma or sub-entity specific pathognomonic alterations. In a project-specific manner, we have applied latest technology platforms at the DKFZ, such as long-read sequencing, single nuclei sequencing as well as spatial proteomics, to gain deeper insights into the biology of the tumors. Mechanistic investigations of selected aberrations is enabled by our expanding model system panel and comprehensive toolkit enabling functional genomics investigations (e.g. CRISPR/Cas9 libraries).
We are currently pursuing the following objectives:
- Targeting critical disease processes: Focus – Activated telomere maintenance mechanisms
- Integrative multi-omics characterization: Focus – Ultra-rare sarcoma
- Development of innovative therapeutic approaches: Focus – Targeted protein degradation, individualized immuno-therapeutics
