The aim of our research is to understand the interplay between cellular oxygen sensing mechanisms occurring over different time-scales. This includes the long-term, transcriptional response mediated by the hypoxia-inducible factor (HIF) pathway, which operates ubiquitously across cells, and the rapid electrophysiological response elicited by hypoxia in specialised cell types, such as the carotid body. We have shown that the HIF-2 isoform spans these two systems in being critical to ventilatory control in response to both acute and chronic hypoxia, in line with its uniquely abundant expression in the carotid body. Our work also describes the pathological role of HIF-2 in cancers of this and related tissues (pheochromocytomas and paragangliomas, PPGLs). This shows that aberrant activation of HIF-2 during development causes a lineage shift to predispose to subsequent PPGL formation, in line with the common occurrence of germline (or post-zygotic but early somatic mutations) mutations in the HIF pathway in these particular tumours.

SPEAKER BIOGRAPHY

Tammie read Natural Sciences, followed by a PhD in mitochondrial bioenergetics with Professor Martin D. Brand, both at the University of Cambridge. This was followed by a post-doctoral study with Professor Peter J. Ratcliffe and Associate Professorship, both at the Nuffield Department of Medicine, University of Oxford. Her research is in understanding the interplay between responses to hypoxia occurring over differing timescales, with a focus on rapid responses to hypoxia. This work was recently awarded a Wellcome Disocvery Award. In October 2024, she was appointed an Associate Professorship at DPAG with Tutorial Fellowship at Trinity College, University of Oxford.