We are the Division of Molecular Neurobiology at the German Cancer Research Center (DKFZ) in Heidelberg, Germany. Here you can learn more about our research interests and lab members.
The central nervous system (CNS) is one of the most fascinating organs in our body, not only because every other organ lays under its control, but also because of its cellular and functional complexity. The CNS contains over a million different neural subtypes and billions of connections. Since I established my laboratory at the DKFZ, our work has focused on understanding the mechanisms underlying neuronal plasticity, which on the one hand underlie malignant transformation in neurooncology and on the other hand are essential to re-build the CNS after injury in regenerative medicine. Over the years, we have established ourselves as an internationally leading group in two fields: (i) the complex functions of CD95 and (ii) adult neural stem cell biology. With these two research lines (RL) we complement our systematic stem cell-centered strategy with mechanistic studies of CD95’s function in homeostasis and disease. In order to study stem cells globally within the CNS in a living organism, we have taken a multidisciplinary approach that combines genetically engineered mouse models with models of injury and cancer and cutting edge technologies in single cell analyses such as lineage tracing, epigenomics, and transcriptomics. We furthermore used advanced cell and animal imaging, and employ powerful in vitro 3D-cell culture models of patient-derived and genome edited human cells.
Our first set of key achievements came from elucidating the function of CD95 in neural, immune and tumor cells. We have discovered that CD95 acts as a potent survival signal for cancer and stem cells, as a proinflammatory factor and activator of angiogenesis. These findings formed the basis for testing inhibition of CD95-activity as a second-line therapy in glioblastoma patients in successful clinical trials. Our current work to identify the molecular events to switch from these pro-disease to pro-apoptotic activity of CD95 will be key to devise novel targeted therapies against cancer, inflammatory and neurodegenerative disorders.
Our second set of achievements focused on the identification of key regulators of stem cell-driven malignant degeneration, regeneration and ageing. In particular, we entered the field of stem cells, by the unbiased identification of CD95 as a factor acting in acquisition of epithelial-to-mesenchimal-like traits and malignant degeneration and in activation of stem cells for repair and survival. In addition, we have identified interferon-gamma as an important activator of stem cells to repair the brain, and the Wnt-antagonist DKK1 as an important pro-aging factor whose inhibition rescues the age-associated cognitive impairment and leads to improvement of mood. Finally, our comparison of neural stem cells to stem cells in the adult pancreas has uncovered common and unique features of stem cell activation in homeostasis and injury that will be instrumental to understand their malignant degeneration. Importantly, our studies on rare stem cells in the adult organs, led us to establish a set of very powerful single-cell technologies. Our laboratory is a pioneer in single stem cell sequencing studies, which has generated many international collaborations with leading groups in the field.
Our future studies will focus on further advancing our understanding of the molecular mechanisms of malignant and normal stem cell activation. Specifically, we want to understand how conversion of aging and inflammation increases cancer risk while decreasing stem cell derived regeneration. These studies integrate analysis of the response of single stem cells at the chromatin, transcriptional and protein level in the living organism. This knowledge will be applied to develop new therapies that prevent malignant degeneration, help to repair the CNS and avoid age-related stem cell decline.