VCKD Members


Volker Hans Haase M.D.,

Department: Medicine


Oxygen Metabolism Group

Principal Investigator: Professor Dr. med. Volker H. Haase

       Chronic kidney disease (CKD) represents a major health burden worldwide, is associated with high cardiovascular morbidity and mortality, and frequently leads to the development of end-stage renal disease (ESRD). In the United States, the prevalence of CKD in the general population is estimated to range from 10 to 15% (all CKD stages; Renal Data System, 2005-2010). Therefore, novel approaches for the diagnosis (biomarkers), the prevention and treatment of CKD are needed to reduce the risk of cardiovascular events, ESRD and death in patients with CKD.

      Hypoxia has been identified as a final and common pathway in the pathogenesis of CKD irrespective of etiology, as demonstrated by the Professor Haase’s group and other laboratories. Professor Haase’s laboratory has a long-standing interest in mammalian oxygen sensing, specifically in the biology of the hypoxia-inducible factor (HIF)/prolyl-4-hydroxylase domain (PHD) pathway and non-HIF-related dioxygenases. PHD enzymes are oxygen sensors that target the α-subunit of HIF for hydroxylation and subsequent proteasomal degradation via the von Hippel-Lindau (VHL) E3 ubiquitin ligase and belong to a family of oxygen- and 2-oxoglutarate (2-OG)-dependent dioxygenases. These enzymes represent excellent drug targets and several compounds are currently in clinical trials for the treatment of renal anemia (Koury and Haase, Nat Rev Nephrol, 2015). Using mouse genetics Prof. Haase’s group identified HIF-1 as the first molecular link between hypoxia and CKD progression (Higgins, JCI, 2007).

      Central hypothesis of Professor Haase’s research program is that hypoxia, the HIF/PHD pathway and other oxygen- and 2OG-dependent dioxygenases play critical roles in the pathogenesis of renal injury and CKD progression through the regulation of metabolic pathways and mitochondrial metabolism. Shifts in cellular metabolism provide specific signals that modulate cellular differentiation and function, cell-cell interactions and inflammation, and thus can lead to maladaptive tissue repair impacting the development and progression of fibrotic diseases, such as CKD. Specifically, Prof. Haase’s group was able to show that changes in epithelial mitochondrial function modulate the function of pericytes and renal microvasculature through changes in renal tissue pO2 (Farsijani, JCI, 2016). Prof. Haase’s group has furthermore shown that the activation of hypoxia responses in renal endothelium modulates inflammatory responses in the context of acute and chronic renal injury (Kapitsinou et al., JCI, 2104).

      The long-term goals of Professor Haase’s research program are to characterize the molecular links between oxygen sensing, renal metabolism and chronic kidney injury. Data generated from this research program are likely to provide general insights into the role of metabolism in the regulation of tissue injury and repair and will therefore be of relevance to multiple organ systems.

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