Research Projects
Main Research Topics of Cellular Oxygen Physiology
General aims
The Cellular Oxygen Physiology Group is exploring the molecular mechanisms and therapeutical consequences of cellular adaptation to changing ambient oxygen conditions like found at high altitude, sites of inflammation or the tumor microenvironment.
Projects:
Functions of the PHD oxygen sensors
- Determination of the hydroxylation activity of PHD1, PHD2 and PHD3
- Identification and characterization of novel PHD-dependent hydroxylation target proteins
- Regulation of PHD oxygen sensor proteins in vitro and in vivo
Role of PHD oxygen sensors and HIF transcription factors in tumor progression
- Functional and diagnostic relevance of PHDs/HIFs in cancer
- Specific functions of HIF-1 alpha and HIF-2 alpha in tumor progression
- Oxygen imaging and feedback regulation of PHD/HIF in solid tumors
Mechanisms of oxygen signalling in pathophysiological conditions
- Oxygen sensing and Epo regulation in the hypoxic and diseased kidney
- Interplay between hypoxic and inflammatory pathways in atherosclerosis and colon cancer
Function of novel heme-containing oxygen-binding proteins
- Hypoxic regulation and pathophysiological role of recently identified globins
PASKIN, a novel metabolic sensory/regulatory protein
- Investigation of small molecules inducing PASKIN kinase activity
- Identification and characterization of PASKIN kinase target proteins
- Behavioural and metabolic analysis of PASKIN knock-out mice
Methods:
- Differential screening of environmentally regulated genes; database mining; screening for novel protein interaction partners
- Recombinant protein expression and purification; antibody production, protein-protein interactions, protein modifications (hydroxylation, phosphorylation, ubiquitinylation), protein localization
- DNA-Protein interactions; transcriptional, translational and stability regulation
- Generation and analysis of genetically modified cell lines (transient and stable overexpression or RNAi-mediated down-regulation) and animals (transgenic and knock-out mice)