Melanoma molecular genetics

In Xiphophorus, the development of naturally occurring melanomas can be initiated by simple crossings, which lead to a pigment cell specific overexpression of Xmrk, a mutationally activated EGF-receptor tyrosine kinase. In order to understand the molecular processes underlying the melanoma-initiating overexpression, we use Next Generation Sequencing (NGS) based approaches (RNA-seq, ATAC-seq and methylome sequencing) as well as cell and molecular biology techniques, including expression pattern analyses and structural and functional promoter studies. Moreover, the development of a mitfa:xmrk transgenic medaka line allows us to perform in vivo studies on transgenic and CRISPR/Cas9 knock-out models. We are also interested in characterizing the role of several tumor modifier candidate genes and perform validation of candidate genes detected in our fish models with established cell culture systems of human melanoma research.

Our goal is to identify global melanoma associated gene expression signatures by comparing RNA expression profiles of different melanoma samples from medaka and Xiphophorus. Once identified, these signatures will be used to search for new therapeutic agents for melanoma therapy.