Professor Dame Frances Ashcroft

As a Professorial Fellow my undergraduate teaching is limited to hosting undergraduate students in Medicine, Biomedical Science and Biochemistry (many of whom are Trinity students) for their final year research project in my lab. I run a multidisciplinary research group in the Department of Physiology Anatomy and Genetics where I also supervise DPhil students and postdoctoral fellows.

There is currently a worldwide epidemic of diabetes. Research in my lab aims to elucidate how a rise in blood glucose stimulates insulin secretion from the beta-cells of the pancreas and why this process is impaired in diabetes. Our previous studies showed that a membrane protein known as the ATP-sensitive potassium channel plays a key role in this process and that mutations in the genes that encode this channel cause a rare genetic form of diabetes known as neonatal diabetes. Our research has enabled most patients with these disease-causing mutations to treat their diabetes with oral tablets instead of insulin injections. Our current work on type 2 diabetes, the most common form of diabetes, has shown that chronically elevated blood sugar levels have deleterious effects on beta-cell function. This leads to a progressive decline in beta-cell function, hastening the transition from impaired glucose tolerance to diabetes and exacerbating the diabetes. We are trying to understand the underlying mechanisms and how this decline can be prevented or reversed. We also continue to study the ATP-sensitive potassium channel and its regulation by glucose metabolism.

You can find out more about my work here.

Usher S.G., Ashcroft F.M., Puljung M.C., ‘Nucleotide inhibition of the pancreatic ATP-sensitive K+ channel explored with patch-clamp fluorometry’, eLIFE 9 (2020), e52775  

Pipatpolkai T., Usher S., Stansfeld P.J., Ashcroft F.M., ‘New insights into KATP channel gene mutations and neonatal diabetes’, Nature Review Endocrinology 16 (2020), 378-393

Haythorne E., Rohm M., van de Bunt M., Brereton M.F., Tarasov A.I., Blacker T.S., Sachse G., Silva dos Santos M., Terron Exposito R., Davis S., Baba O., Fischer R., Duchen M.R., Rorsman P., MacRae J.I., Ashcroft F.M., ‘Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells’, Nature Communications 10 (2019), 2474

Puljung M., Vedovato N., Usher S., Ashcroft F.M., ‘Activation mechanism of ATP-sensitive K+ channels explored with real-time nucleotide binding’, eLIFE (2019), 8:e41103

Rohm M., Savic D., Ball V., Curtis M.K., Bonham S., Fischer R., Legrave N., MacRae J.I., Tyler D.J., Ashcroft F.M., ‘Cardiac dysfunction and metabolic inflexibility in a mouse model of diabetes without dyslipidaemia’, Diabetes 67 (2018), 1057-1067

Rorsman P., Ashcroft F.M., ‘Pancreatic β-cell electrical activity and insulin secretion: Of mice and men. Physiological Reviews’, 98 (2018), 117-214