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David Mole

Associate Professor, Senior Clinical Research Fellow, Group Head / PI, Consultant Physician

Oxygen is of fundamental importance for most living organisms. In higher animals such as human beings appropriate delivery of oxygen (by the lungs, heart, blood, circulation and blood vessels) to all the cells is a considerable challenge - particularly as inadequate delivery will impair metabolism whereas excess oxygen is toxic. Not surprisingly, inappropriate oxygen delivery to cells plays a major role in many human diseases.
The group is analysing transcriptional responses to oxygen availability that regulate processes such as angiogenesis, cellular energy metabolism and proliferation/survival signals that operate in development. An important focus is on the hypoxia inducible factor (HIF) system that is regulated through oxygen dependent targeting of the transcription factor for ubiquitin mediated proteolysis. The group has demonstrated that this involves a novel method of protein recognition in which oxygen sensitive prolyl hydroxylation of HIF regulates ineraction with the von Hippel-Lindau tumour suppressor E3 ubiquitin ligase. Current lines of investigation include the general importance of prolyl hydroxylation as a signalling mechanism, the structural analysis of oxygen sensitive prolyl hydroxylases, the role of the HIF system in development, ischaemia/hypoxic disease, and tumour biology, and the interaction between oxygen and iron signalling

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