HIF-2 and the Carotid Body: R Jean Banister Prize Lecture 2023

Dr Tammie Bishop is an Associate Professor at University of Oxford, UK where she leads a group investigating the role of HIF-2 in the carotid body, a sensory structure which mediates ventilatory responses to low oxygen or hypoxia.

The focus of her research is in understanding 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. Her work shows 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. Her work also describes the pathological role of HIF-2 in cancers of this and related tissues (collectively termed pheochromocytomas and paragangliomas or 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.