Cellular Compartments and New Molecules Interacting in Hypoxia-Signaling and Associated Diseases - Thomas Kietzmann
The lack of oxygen (commonly termed hypoxia), the appearance of reactive oxygen species (ROS) and excessive protein synthesis and degradation are associated with the pathogenesis of diseases such as diabetes mellitus, atherosclerosis, thrombosis, pulmonary hypertension as well as with cancer. Our vision is to understand the mechanisms by which ROS from different cell compartments and ubiquitin-specific proteases modify the cellular gene and protein expression profile in response to the ambient O2 tension. While the existing body of work provides a general picture how O2 affects gene expression, metabolism, and protein degradation, a number of issues remain uncertain. Therefore, it is the overall aim of our work to understand the mechanistic link between hypoxia-associated diseases, compartment-specific changes of ROS levels and modulation of protein degradation in vivo and in vitro.