Summary

Massive parallel sequencing has provided the means to rapidly identify all mutations that are present in a tumor as well as functionally describe disease related genes. Nevertheless, in the future it will be crucial to add additional molecular data to advance novel therapeutic and diagnostic strategies. In particular, the addition of functional data promises to broaden the field and to allow a more personalized evaluation improving treatment predictions.

The research group of Frank Buchholz is using different strategies to dissect gene function relevant to human disease, such as cancer biology and stem cell research. The laboratory has developed an innovative platform to perform large-scale RNAi experiments in mammalian cells and in mice. Endoribonuclease prepared siRNA (esiRNA) is used for efficient and specific knockdown in genome wide screens to identify and characterize genes relevant to cancer biology and differentiation. Furthermore RNAi profiling in primary cancer cells is performed with the aim to implement functional data into personalized medicine. To achieve this goal the established expertise on RNAi profiling is currently translated to different tumor entities.

In addition, the laboratory is using innovative genome-editing technologies to unmask mutations that drive cell growth and viability in cancer cells. As programmable scissors the CRISPR/Cas9 technology allows for example cleavage of DNA at predefined sites mutated in the genome of cancer cells. Based on the achieved successful and promising results it is planned to further develop this technology for use in primary patient material as a diagnostic tool to pinpoint specific cancer vulnerabilities.

An additional research pillar of the laboratory represents the use of directed molecular evolution to evolve site-specific recombinase for precision genome editing. By applying substrate-linked directed evolution, in combination with rational design, site-specific recombinases are being generated with therapeutic potentials as they are representing proven tools that allow safe genetic manipulations of whole organisms. Therefore, it is planned to generate new designer recombinases that correct genetic alterations found in different human diseases, including cancer.