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Roland H. Wenger

Institute of Physiology, University of Zürich, Switzerland

Wednesday, October 23, 09:00 - 09:25

Modulating the human hypoxia response

Protein stability and transcriptional activity of hypoxia-inducible factor (HIF) α subunits is regulated by oxygen-sensing protein hydroxylases. When oxygen is abundant, HIFα subunits are hydroxylated and rapidly degraded; but when oxygen is scarce, HIFα subunits remain stable and form active heterodimeric HIF transcription factors which induce a large number of genes involved in the adaptation to hypoxic conditions with pathophysiological implications for erythropoiesis, angiogenesis, cardiovascular function and cellular metabolism in healthy and cancerous tissues. Oxygen-sensing is regulated by the co-substrate-dependent activity and hypoxia-inducible abundance of the HIFα prolyl-4-hydroxylases (PHDs) which trigger HIFα stability even under low oxygen conditions. Based on the subtle balance between PHD and HIFα levels/activities, these two factors form the core of a mutually adjusted, self-adaptive oxygen sensing system. A number of upstream regulators of the PHDs trigger this oxygen sensing system. Moreover, the recent identification of novel downstream targets of PHDs suggests that cellular oxygen sensing by PHDs cross-talks to additional signalling pathways, in addition to the HIF system.


Roland H. Wenger is Professor for Physiology at the University of Zurich. Born in Biel/Bienne, he studied chemistry at the University of Berne where he also did his PhD thesis at the Theodor-Kocher-Institute from 1987 to 1990. Following a post-doctoral fellowship at the Max-Planck-Institute for Immunobiology in Freiburg i.Bsg. from 1990 to 1993, he moved to the Institute of Physiology, University of Zürich, where he obtained the Venia legendi in Physiology in 1999. From 2000 to 2001 he was University Lecturer at the University of Lübeck and from 2001 to 2003 Associate Professor at the University of Leipzig.