Citation | Understanding oxygen sensing processes such as that regulating the erythropoietin (Epo) gene has been a longstanding goal in medical research because of the importance of oxygen homeostasis in clinical physiology. Ratcliffe's group worked initially on Epo regulation but made the important discovery that this response was (unexpectedly) part of a widespread transcriptional response with many other medically important functions (eg regulation of angiogenesis, cellular metabolism, matrix metabolism). Over the last 10 years Ratcliffe and his team have analysed the oxygen sensing/signal transduction pathway in detail and have succeeded in obtaining a molecular analysis from the oxygen sensing process (definition of a novel family of 'sensing' dioxygenases) to the mode of transcriptional regulation. This work has far-reaching importance in the understanding of neoplastic and ischaemic/hypoxic disease processes. |