Studying environmental and molecular toxicology
The Vogel research group focuses on the function of receptors for xenobiotics and inflammatory signaling to understand molecular mechanisms of the development of chronic inflammatory diseases promoted by exposure to environmental toxicants.
We investigate how the innate immune system is affected after exposure to environmental pollutants during and after differentiation. During an infection, dendritic cells and macrophages acquire defined identities culminating in the generation of an orchestrated immune response. This process is a precise temporal regulation of genes that program developmental decisions as well as the function of antigen presenting cells to regulate T cell differentiation for instance. Of the many factors that influence the function of the cells of the innate immune system, cytokines and chemokines are important regulators in a fine-tuned immune response. Activation of receptors and transcription factors such as Toll like receptors (TLR) and NF-kB is believed to be critical to orchestrating key molecular events in the transcriptional regulation of genes controlling a classical immune response. More recently the physiological role of the Aryl hydrocarbon receptor (AhR), a receptor protein for environmental chemicals and dietary components, has been identified as a transcriptional regulator of lymphoid cell subsets critical to mucosal immunity for instance. We believe that activation of AhR by toxic ligands and the resulting disturbance of TLR and NF-kB signaling pathways are the origin of deregulated immune response mechanisms leading to the devastating consequences of immune disorders.
Our mission is to gain a deeper understanding of the functional impact and molecular mechanisms of beneficial and detrimental ligands interacting with the AhR and cells of the innate immune system. Using both in vitro models (macrophages, dendritic cells) and mouse in vivo models, we intend to gain molecular insights into the development of chronic diseases mediated by environmental pollutants. These insights will be invaluable to device strategies to program and reprogram cells towards a particular immune response allowing the development of new therapeutic substances and strategies.
Why do we study immune disorders and AhR? Autoimmune diseases including allergy, asthma, and even cancer are based on or associated with non-functional or deregulated immune responses and remain the leading cause of death worldwide despite improved prognosis and aetiological understanding. In addition to genetic variants that result in the predisposition to disease, environmental elements may trigger or exacerbate the disease through interaction with AhR. Due to the prevalence of chronic inflammatory diseases, it is critical to gain deeper understanding of the genetic networks driving the development and function of immune cells in order to devise strategies to combat immune disorders and engineer regenerative strategies.
- Analysis of molecular mechanisms causing immunotoxic effects as a result from exposure to environmental pollutants.
- Identification of molecular markers (biomarkers) for risk assessment of the development of chronic diseases (autoimmune diseases, cancer) caused by exposure.
- Development and application of in vitro models as alternatives to animal experiments. One major topic is the detection and assessment of the inflammatory and oxidative stress responses caused by chemicals from combustion processes.
- Genotoxicity of fuel emission samples. The Single Cell Gel Electrophoresis assay (also known as Comet Assay) is a sensitive technique for the detection of DNA damage at the level of the individual eukaryotic cell. Human monocytic cells are used to evaluate the potential damage to DNA caused by exposure to fuel emission samples.