Professor Margaret Ashcroft

Research Overview

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.

We are interested in how the oxygen sensing machinery controls cell function and adaptive processes that are associated with a variety of diseases including cancer, renal disease and cardiovascular disease. Our work primarily focuses on the heterodimeric transcription factor family, hypoxia inducible factor (HIF). HIF-1, the prototype of the family is composed of α and β subunits. Regulation of HIF-1 activity is primarily via the HIF-1α subunit, which is rapidly turned over via ubiquitin-mediated degradation by the proteosome; however, the HIF-1β subunit is constitutively expressed. In response to low oxygen tension (hypoxia), HIF-1α protein is stabilised and localises to the nucleus where it binds to HIF-1β and recruits transcriptional coactivators.

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.