Balfour lecture 2010 – Sarah Flanagan

Sarah Flanagan is a Sir Henry Dale Fellow at the University of Exeter whose work focuses on the genetics of neonatal diabetes and congenital hyperinsulinism, two opposing disorders of insulin secretion.  The overarching aim of her research is to gain novel insights from rare monogenic disease to improve understanding of biological pathways which are important for the development of more common conditions such as type 1 and type 2 diabetes.

Sarah’s doctoral work focused on studying the pancreatic K-ATP channel genes KCNJ11 and ABCC8, in which activating mutations cause a loss of insulin secretion leading to neonatal diabetes, and inactivating mutations cause increased insulin secretion and congenital hyperinsulinism.  Identifying a mutation in a K-ATP channel gene has major implications for the treatment of neonatal diabetes with patients being able to transfer from insulin injections to sulphonylurea tablets.  Similarly identifying a K-ATP channel mutation in a patient with medically-unresponsive hyperinsulinism will help to guide surgery in those requiring pancreatectomy.  Given the importance of genetic testing for this condition, Sarah has recently formed a partnership with the charitable organisation, Congenital Hyperinsulinism International, to ensure that patients throughout the world have access to genetic testing regardless of their economic status.

Following her PhD Sarah re-focused her efforts on gene discovery and identified 5 novel genes for neonatal diabetes and 3 new genes for congenital hyperinsulinism.  This work provided the first conclusive evidence to support the role of these genes within the human pancreas.  Currently Sarah leads the hyperinsulinism genetic research in Exeter where she is investigating the underlying mechanisms of disease in the 50% of patients without a genetic diagnosis.  Sarah’s work in the field of metabolism has recently been recognised by her receipt of the 2018 Morgagni Silver Medal Award.