Nick Talbot - Cardiac Sciences - 'Modulators of the hypoxia-inducible factor (HIF) pathway and cardiorespiratory physiology'

The hypoxia-inducible factor (HIF) signalling pathway regulates the cellular response to hypoxia, but also appears to coordinate systemic responses to hypoxia, including the pulmonary vascular and ventilatory responses. In humans, the role of the HIF pathway in cardiorespiratory physiology has been characterised to date mainly by studying small groups of patients with genetic disorders, for example those with mutations in the HIF proteins themselves, or in the associated prolyl hydroxylase domain (PHD) oxygen sensing enzymes. Recently, a number of drugs have been developed that influence HIF signalling. Roxadustat, for example, is licensed for treatment of renal anaemia, and acts by upregulating the HIF pathway through PHD inhibition. However, the effects of this drug on systemic responses to hypoxia are not well understood. This project, funded in part by a Medical Research Council award to Dr Mary Slingo, will initially examine the effects of roxadustat on physiological responses to hypoxia in healthy volunteers, with a view to longer term studies in patients receiving this drug in the clinical setting.