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 and FIH oxygen sensors

  • Determination of the hydroxylation activity of PHD1, PHD2, PHD3 and FIH
  • Identification and characterization of novel PHD- and FIH-dependent hydroxylation target proteins
  • Regulation of PHD and FIH oxygen sensor proteins in vitro and in vivo
  • Oxygen-dependent regulation of energy metabolism

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-1alpha and HIF-2alpha in tumor progression
  • Oxygen imaging and feedback regulation of PHD/HIF in solid tumors

Mechanisms of oxygen signaling in pathophysiological conditions

  • Oxygen sensing and Epo regulation in the hypoxic and diseased kidney
  • Interplay between hypoxic and inflammatory/fibrotic pathways in the diseased kidney, atherosclerosis and colon cancer

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, ubiquitination), 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)