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Iona Cuthbertson

Iona  Cuthbertson

BHF PhD candidate


Departments and Institutes

Department of Medicine:

Research Interests

Pulmonary Arterial Hypertension (PAH) is a devastating disease, in which gradual obliteration of pulmonary microvasculature leads to increased right ventricular pressure, and eventually heart failure. There is no cure, and treatments minimally improve patients’ quality of life. Dysfunctional endothelial cells (EC) are key to the development of PAH and are characterised by excessive proliferation and resistance to apoptosis. Our lab has shown that PAH ECs also upregulate expression of glycolytic enzyme pyruvate kinase M2 (PKM2) and upstream splicing factor polypyrimidine-tract-binding protein (PTBP1). Further our lab has shown that inhibition of PTBP1 normalises glycolysis and cell proliferation rates to those observed in healthy cells. In cancer, therapeutic agents which inhibit PTBP1 and PKM2 potently suppresses cell proliferation by suppressing glycolysis, however, whether these agents are viable for the treatment of PAH EC dysfunction is not known. My PhD project investigates this using in vitro EC culture and in vivo models of PAH treated with these agents, and subsequent analysis of protein and gene expression in addition to several metabolic and functional parameters.

Keywords

endothelial cells ; pulmonary arterial hypertension ; metabolism ; PTBP1, PKM2

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