Researcher Database
Prof. Dr. Frank Buchholz
Fetscherstraße 74
01307 Dresden
Program
Molecularly Targeted Therapy (MTT)
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.
DKTK Junior Group Leader for Cancer Systems Biology
Single-cell approaches have not only revealed a wide variety of cell states, characterized by cells exhibiting striking differences in their transcriptional profile, but have also illuminated the mechanisms underlying state transitions in health and disease. Cellular plasticity and adaptive state changes have recently emerged as a basis for therapeutic resistance in cancer, and a better understanding of how cell state transitions are regulated is critical to develop therapeutic approaches that can overcome therapy resistance.
Our research focuses on understanding the mechanisms driving non-genetic cellular heterogeneity and therapy resistance in malignancy. Using novel single-cell sequencing approaches, we seek to develop new experimental and computational strategies to define altered cell states in both, cancer and immune cells. Our aim is to leverage a data driven strategy combined with single cell genomics and systems biology to address the challenges posed by heterogeneity in cancer, and to develop new strategies to overcome it, with the aim of translating laboratory-based findings into the clinic.