Biomarker in occupational medicine

The research group concentrates on cellular responses to exposure to hazardous substances/xenobiotics. To achieve this objective, the fate of xenobiotics is monitored from the uptake/metabolisation to the occurrence of adverse responses. The group uses cell models (2D and 3D models) that are exposed to xenobiotics time- and dose-dependently. This study design captures cellular responses ranging from no effect over low dose response to definite toxic effects enabling the analysis of the transition from adaptive to adverse responses. Mechanistic studies of this transition are essential for the protection of humans.

A variety of biological-analytical methods are used to investigate underlying mechanisms. One focus of the investigations lies on changes in the metabolism of cells in response to exposure, which are determined using a metabolomic approach. In order to characterize the transition from an adaptive to an adverse response, various biomathematical methods are applied.

Selection of research projects:

• Modelling of dose-dependent changes in the energy metabolism of urothelial cells after exposure to 3-nitrobenzanthrone (DFG SCHM 1207/5-1):
  3-Nitrobenzanthrone (3-NBA) is a mutagenic compound in diesel engine emissions. So far, only a few studies adressing the mode of action in lung and liver cells have been carried out. Diesel engine emissions are also discussed as triggers of urinary bladder carcinomas. In this study, the cellular effects in bladder cells on exposure to 3-NBA have been investigated. Changes of the energy metabolism have been analyzed metabolically. These changes are currently being mathematically modelled in a systems biology approach in cooperation with the research group of PD Dr. Maria Neuss-Radu (Department of Applied Mathematics).

• Analysis of calcium-mediated changes of cellular metabolism in lung cells in response to an exposure to carbon black (funded by the scholarship program „Promotion of Equal Opportunities for Women in Research and Teaching“):
  In this project, alveolar and bronchial lung cells have been exposed in vitro to carbon black as a model substance for nanoparticles. A metabolomic (flux) approach and a large number of assays have been used to assess changes in the oxidative state of the cells. Gene analyses provide information on the role of MAP kinases (mitogen-activated protein kinases).

• Nanoparticles and their corona (funded by the Cluster of Excellence Engineering of Advanced Materials, subproject NS2):
  As soon as nanoparticles come into contact with biological fluids, a so-called corona is formed around the particles, which consists of proteins, but also lipids, sugars and other molecules. The project has developed a method for gradually „peeling“ the corona. This enables more detailed investigations of components that are bound to the particles to varying degrees. Furthermore, smaller molecules of the corona have been identified for the first time by mass spectrometry (GC-MS) and compared between particles of different toxicity.

• Hazard and risk assessment of contact allergens in skin models:
  The combinatorial effect of allergens and irritants on the skin has not been well investigated. In this project the effect of different combinations of allergens and irritants is tested according to OECD guidelines. In addition, a 3D skin model (reconstructed skin model) was developed to investigate signaling pathways and cell-cell communication.