Tammie Bishop

I am an Associate Professor of Cellular and Integrative Physiology in the Department of Physiology, Anatomy and Genetics.

I read Natural Sciences at Cambridge, followed by a PhD in mitochondrial bioenergetics with Martin Brand at Cambridge. I subsequently came to Oxford as a post-doctoral scientist to research hypoxia signalling with Peter J. Ratcliffe.

I currently lead a group investigating rapid responses to low oxygen (hypoxia), as exemplified by the increase in breathing in response to hypoxia that is mediated by the peripheral arterial chemoreceptor: the carotid body. This work has recently been awarded a Wellcome Discovery Award.

Oxford has a long history of discovery in oxygen sensing, beginning with early pioneers into altitude research: John Scott Haldane and Mabel FitzGerald, through to the discovery of the HIF pathway by Peter J. Ratcliffe. We strive to build on this legacy by expanding our horizons into hypoxia signalling.

I lecture and give tutorials on ‘Physiology and Pharmacology’ for the first-year Medicine courses; ‘Applied Physiology and Pharmacology’ for the second-year Medicine course, and ‘Body and Cells’ for the first-year Biomedical Sciences course. I also give lectures and tutorials in the Final Honour School (FHS) option: ‘Applied Human Physiology’. 

I teach first-year students, in groups of two or three, throughout the year (typically five tutorials per term). Teaching of second-year medical students is conducted in a similar manner but only over the first two terms (the 1st BM Part 2 examination is at the beginning of the third term). 

I also supervise undergraduate research projects and extended essays, all of which are key parts of the final-year course. In addition to undergraduate teaching, I supervise graduate research students studying for DPhils.

The focus of my 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 in specialised cell types such as the carotid body to mediate hypoxic ventilatory control. Specifically, my team discovered a role for HIF-2 in hypoxic ventilatory control and carotid body function.

Regulation of ventilatory sensitivity and carotid body proliferation in hypoxia by the PHD2/HIF-2 pathway. Hodson_EJ, Nicholls_LG, Turner_PJ, Llyr_R, Fielding_JW, Douglas_G, Ratnayaka_I, Robbins_PA, Pugh_CW, Buckler_KJ, Ratcliffe_PJ*, Bishop_T*. (2016) The Journal of Physiology 594: 1179-1195. * Joint senior and corresponding authors. PMID: 26337139. The first paper to define a role for HIF-2alpha in ventilatory control in response to acute and sustained hypoxia. This shifted the thinking in the hypoxia field by: demonstrating the importance of HIF-2, rather than HIF-1, in hypoxic ventilatory control; linking the HIF-2 transcription factor in mediating acute hypoxic responses.

PHD2 inactivation in Type I cells drives HIF-2α-dependent multilineage hyperplasia and the formation of paraganglioma-like carotid bodies. Fielding_JW, Hodson_EJ, Cheng_X, Ferguson_DJP, Eckardt_L, Adam_J, Lip_P, Maton-Howarth_M, Ratnayaka_I, Pugh_CW, Buckler_KJ, Ratcliffe_PJ*, Bishop_T*. (2018) The Journal of Physiology 596: 4393-4412. *Joint senior and corresponding authors. PMID: 29917232. Defined carotid body Type I cells as the critical cell autonomous proliferating population in hypoxia. In agreement, inactivation of HIF-2 in Type I cells markedly impairs hypoxic ventilatory control and carotid body proliferation whilst HIF-2 stabilisation with genetic inactivation of Phd2 results in the formation of paraganglioma-like carotid bodies.

Marked and rapid effects of pharmacological HIF-2alpha antagonism on hypoxic ventilatory control. Cheng_X, Prange-Barczynska_M, Fielding_JW, Zhang_M, Burrell_AL, Lima_JDCC, Eckardt_L, Argles_ILA, Pugh_CW, Buckler_KJ, Robbins_PA, Hodson_EJ, Bruick_RK, Collinson_LM, Rastinejad_F, Bishop_T*, Ratcliffe_PJ*. (2020) Journal of Clinical Investigation 130: 2237-2251. *Joint senior and corresponding authors. PMID: 31999648. The first paper to define a role for HIF-2alpha antagonists in non-renal tissues; these have marked and rapid effects on hypoxic ventilatory control when administered at anti-cancer doses. This work also suggests a potential functional role for the HIF-2 PAS B domain e.g. in binding endogenous ligands.

Developmental role of PHD2 in the pathogenesis of pseudohypoxic pheochromocytoma. Eckardt_L, Prange-Barczynska_M, Hodson_EJ, Fielding_JW, Cheng_X, Lima_JDCC, Kurlekar_S, Douglas_G, Ratcliffe_PJ*, Bishop_T*. (2021) Endocrine-Related Cancer 28: 757-772. *Joint senior and corresponding authors. PMID: 34658364. This paper (awarded the Society for Endocrinology Award (2022)) models PPGLs, in which inherited mutations of the HIF pathway are common, by demonstrating that HIF-2 activation in the adrenal medulla during the developmental window causes a lineage shift towards an immature cell population which predisposes towards subsequent development of PPGLs.

Hif-2alpha programmes oxygen chemosensitivity in chromaffin cells. Prange-Barczynska_M, Jones_HA, Sugimoto_Y, Cheng_X, Lima_JDCC, Ratnayaka_I, Douglas_G, Buckler_KJ, Ratcliffe_PJ*, Keeley_TP*, Bishop_T*. (2024) in print Journal of Clinical Investigation; BioRxiv DOI: https://doi.org/10.1101/2023.07.14.548982. *Joint senior and corresponding authors. Defined HIF-2alpha as a lineage specifier conferring oxygen chemosensitivity on chromaffin cells, opening a new entry point for mechanistic studies of rapid oxygen sensing pathways.

Hif-2alpha: the interface between oxygen-sensing systems in physiology and pathology. Bishop_T and Ratcliffe_PJ. (2025) in print Physiology. PMID: 39946558. doi: 10.1152/physiol.00043.2024.

Fluorescent image of the carotid body (an oxygen chemoreceptor located at the base of the arteries supplying the head and neck), whose cells sense a reduction in oxygen and trigger hyperventilation. Red stains endothelial cells and blue stains nuclei. Credit: James W. Fielding.

In situ hybridisation for Hif-2 mRNA (pink) in the carotid body, showing high levels of expression, in line with the importance of HIF-2 in oxygen chemosensing by this organ. Credit: Emma J. Hodson.