Junior Research Group Soft-Tissue Sarcoma
Dr. Ana Banito
Endogenous tagging of the SS18-SSX fusion oncogene using CRISPR/Cas9-mediated homologous directed repair with Flag-HA epitopes in synovial sarcoma cells. The figure shows detection of SS18-SSX using anti-HA-tag immunofluorescence (red). This tool allowed to study genome-wide occupancy and protein-protein interactions of this oncogenic driver.
© dkfz.de
Sarcomas are an extremely heterogeneous group of mesenchymal tumors that arise in a multitude of tissues and cell types. Several genetic events have been identified in different sarcoma sub-types, but very few models were developed to study their role in tumorigenesis aiming at exploiting them as therapeutic vulnerabilities. As a result, the treatment of sarcoma has had extremely limited advancement in treatment options compared to other cancers. Thus, the generation of in vitro and in vivo models for sarcoma research is urgently needed, to provide insights into the pathobiology of these tumors and discover novel vulnerabilities in these often lethal but yet understudied diseases. A common molecular mechanism Many types of soft tissue sarcomas arising in children and young adults have a unifying underlying genetic mechanism, where chromosomal translocations generate fusion oncoproteins that serve as drivers of the disease. This genetic simplicity provides an exceptional opportunity to develop effective and specific therapies. My past research has applied cutting edge technology to define epigenetic vulnerabilities associated with the SS18-SSX gene fusion, the defining event in synovial sarcoma, and to study its oncogenic molecular mechanism. Our current goal is to combine a toolbox consisting of CRISPR/Cas9, RNAi technology and mouse modeling tools to systematically address key genetic and epigenetic mechanisms in the pathobiology of pediatric sarcomas. Our goal is to comprehensively study the impact of gene fusions and other genetic drivers in sarcomagenesis, uncover specific vulnerabilities they create, ultimately aiming at maximizing the potential for rapid clinical translation.
