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Professor Margaret Ashcroft

Hypoxia signalling


Research themes

Vascular Medicine:

Research Interests

The main goal of the Ashcroft laboratory is to understand the key cellular mechanisms involved in oxygen sensing and hypoxia signalling in mammalian cells. In particular, we have a strong interest in the hypoxia inducible factor (HIF) family of transcription factors and their role in cancer, renal disease and cardiovascular disease.

 

Research Aims

Our main goals are to:

1) Evaluate known and novel regulators of the hypoxia/HIF signalling with particular focus on link between mitochondria and the cellular oxygen-sensing machinery.

2) Investigate the key cellular mechanisms regulating hypoxia/HIF signalling in mammalian cells and elucidate how these are mechanistically linked to disease.

3) Identify and develop strategies to exploit hypoxia/HIF signalling in disease.

Keywords

cancer ; reperfusion ; mitochondria ; hypoxia ; HIF ; angiogenesis ; cardioprotection ; ischaemia

Key Publications

Recent Publications

CHCHD4 confers metabolic vulnerabilities to tumour cells through its control of the mitochondrial respiratory chain.   Thomas LW, Stephen JM, Esposito C, Hoer S, Antrobus R, Ahmed A, Al-Habib H, Ashcroft M.

Cancer Metab. 2019 Mar 6;7:2. doi: 10.1186/s40170-019-0194-y. eCollection 2019.

Exploring the molecular interface between hypoxia-inducible factor signalling and mitochondria.   Thomas LW, Ashcroft M.  

Cell Mol Life Sci. 2019 Feb 14. doi: 10.1007/s00018-019-03039-y. [Epub ahead of print] Review.

VHL-mediated regulation of CHCHD4 and mitochondrial function. Briston T., Stephen J., Thomas L.W., Esposito C., Chung Y.L., Syafruddin S., Turmaine M., Maddalena L., Greef B., Szabadkai G., Maxwell P.H., Vanharanta S. and Ashcroft M. Front Oncology (2018) 8: 388.

The mitochondrial oxidoreductase CHCHD4 is present in a semi-oxidized state in vivo. Erdogan A.J., Ali M., Habich M., Salscheider S.L., Schu L., Petrungaro C., Thomas L.W., Ashcroft M., Leichert L.I., Roma L.P. and Riemer J. Redox Biol (2018) 17: 200-206.

CHCHD4 regulates intracellular oxygenation and perinuclear distribution of mitochondria. Thomas L.W., Staples O., Turmaine M., Ashcroft M. Frontiers in Oncology (2017) 7: 71.

 

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