Raphaela Fritsche

PostDoc Jul 2016 -

Berlin Institute of Health (BIH), Max Delbrück Center for Molecular Medicine

Neuroblastoma (NB) is the primary cause of death from pediatric cancer deriving from neural crest precursor cells. Its clinical impact and biological heterogeneity leading to a highly aggressive malignancy drive the translational research effort. In the last years, analyzing tumor metabolism in adult solid tumors has an enormous boost of interest, however, only minor attention has been focused on childhood cancer. Despite intensive research, improvements in clinical outcome of NB have been achieved mostly for low- and intermediate-risk tumors. To gain new insights into NB pathogenesis we will analyze several high-risk NB cell lines and a cohort of NB tissue samples using MS-based proteomics and metabolomics techniques. As it is known that NB tumors show dependency on glycolysis, targeting major branching points may be a promising therapeutic strategy.

PostDoc May 2013 - Jun 2016

Berlin Institute of Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine

It is well known, that oncogenic signaling directly induces metabolic dependencies. Several studies have shown the importance of metabolic changes induced by oncogenic KRAS. Further, nutrient uptake and metabolic alterations are under control of the RAS oncogene leading to increased glucose consumption, glycolysis and lipid synthesis. A result of this metabolic reprogramming is the dependence of KRAS transformed cells on glucose availability. However, the precise metabolic effects downstream of oncogenic RAS signaling in cancer cells have not been completely elucidated. Aiming to investigate the impact of activated KRAS and BRAF onto tumor cell metabolism, signaling and protein abundance in a nutrient altered microenvironment using cutting edge mass spectrometry-based metabolomics (pSIRM) and proteomics techniques (part of OncoPATH). With the mentioned approach we were able to get new insights into molecular biology of colorectal cancer. We found that oncogenic signaling directly induces metabolic dependencies. Therefore a therapeutic window opens that can be addressed by metabolic therapies.

Colorectal cancer are invariably less well-oxygenated than normal tissues from which they arose. Hypoxia induces a wide range of biological changes including decreased proliferation, increased expression of drug resistance genes, selection of apoptosis-resistant clones or facilitation of tumor invasion and metastasis. Tumors which possess low oxygen regions have a poorer prognosis than well oxygenized ones. Hypoxic conditions result in selective pressure on cancer cells and their ability to survive in a hypoxic microenvironment. However, the escape mechanisms of cancer cells under hypoxic stress have not been fully characterized. Trying to find out, how KRAS and BRAF oncogenes signaling through the same pathway can give rise to distinct tumor behavior under hypoxic stress, we could show that BRAF and KRAS can be influenced by hypoxia resulting in activation of multiple signaling and metabolic pathways. Therefore we suggest, that hypoxia is an important selective force in the mutational evolution of colorectal tumors.

PostDoc Jun 2008 - Apr 2013

Institute of Theoretical Biology, Humboldt University of Berlin

We are investigating how mammalian cells process information about intra- and extracellular cues through their intra-cellular signalling and gene-regulatory networks, how these networks dysfunction in disease and how these networks can be modulated by drugs. We are an interdisciplinary team of experimentalists and theoreticians and utilise mathematical models and theoretical concepts as well as quantitative and high throuput experimental approaches to analyse signalling and gene expression. Part of FORSYS and OncoPATH (formerly ColoNET).

PostDoc Mar 2008 - May 2008

Institute of Pathology, Charité-Universitätsmedizin Berlin

Scientific employee in the group of C. Sers, Institute of Pathology. After thesis, ongoing work on Ephrin receptor ligand interaction.

PhD student Sep 2003 - Feb 2008

Institute of Pathology, Charité-Universitätsmedizin Berlin

Thesis with title "Genom-wide expression profile of skeletal tumors and functional analysis of Ephrins and CD52 in osteosarcoma and giant cell tumors of bones".

Freie Universität Berlin 1999 - 2003

Field of study: Biology
Degree: Diploma