Division of Signal Transduction and Growth Control
Prof. Dr. Peter Angel
The Division was working on the characterization of the genetic response of organisms and their cells to external signals (growth factors, inflammation-related cytokines, carcinogens and tumor promoters), employing genetically modified mouse models (which replicate features of human diseases) and cell- and organ cultures derived thereof. We wanted to define and characterize altered gene functions, which result in imbalanced signaling pathways and downstream genetic programs that form the basis for acquired capabilities of uncontrolled cell growth, evasion of apoptosis, sustained angiogenesis and, finally, enhanced tissue invasion and metastasis. To date, we have applied genetically modified animal models, in vitro organ systems, and genome-wide expression analyses in order to decipher the individual functions of AP-1 subunits. Our study of individual AP-1 subunits with regard to their regulation, as well as the identification of distinct targets genes and genetic programs critically involved in cancer development and progression, has yielded major contributions to our current understanding of genetic programs in physiological (e.g. embryogenesis, vascular biology/angiogenesis, wound healing) and pathological processes (chronic inflammation, tumorigenesis). In collaboration with clinical partners, these studies, accompanied by analyses of human tumor samples, aim ultimately to define novel molecular markers for diagnosis and therapeutic intervention.
With the goal of bridging basic science and translational research, and in collaboration with partners at the DKFZ, Heidelberg University and external partners, our program has focused on intra- and intercellular signaling pathways and downstream genetic programs in cancer to develop and evaluate molecules as potential biomarkers or drug targets. We have utilized state-of-the-art methods including modified transgenic mice, various tumor models, interspecies heterologous co-culture cell systems, genome-wide expression and epigenetic analyses combined with systems biological approaches, and molecular and cellular biology to study tumor-relevant genetic networks. We have focused on mechanisms of cell-cell communication in wound healing, and cross-talk between tumor cells and cells of the microenvironment (endothelial, mesenchymal and immune cells). Attention was especially focused on (soluble) mediators of cell communication as well as downstream signaling pathways and genetic programs initiated in the corresponding target cells.
Our main projects concerned:
1. Physiology and pathology of wound healing: genetic programs of cell proliferation, migration and differentiation.
2. Function of the cell surface protein podoplanin in brain and skin tumors.
3. Genetic and epigenetic programs of tumor angiogenesis and vessel physiology; role of the tumor stroma.
4. Function of the receptor RAGE and its ligands (S100 proteins) in inflammation and cancer.
FUTURE OUTLOOK
Since the Division Head is approaching retirement experimental work of this Division will end in May 2024.
