Can you describe the aim of this project in 10 words?
Releasing the “insulin handbrake” for improving glycemic control in diabetes.
What have you already discovered about neuropeptide Y ?
The NPY family comprises three peptides (NPY, PYY and PP) and five receptors (Y1, Y2, Y4, Y5 and Y6). Central NPY plays a major role in the regulation of appetite and energy expenditure by activating central Y1 receptors in the hypothalamus. It is well established that NPY contributes to the development of obesity by promoting energy intake and decreasing energy expenditure. In 2014, I co-authored research that showed the central Y6 receptor regulates energy metabolism and circadian rhythms.
In 2017, I discovered that the Y1 receptor is expressed in mouse and human islets. Islet Y1 receptor plays a major role in the regulation of insulin secretion and that inhibition of Y1 receptors improves β-cell function and islet transplantation outcomes. These exciting studies open up the possibility for the use of Y1 antagonist as a therapeutic option to enhance β-cell function and islet transplantation outcome in a clinical setting.
What aspect of this current research excites you the most?
The access to human tissue samples excites me the most and the ability to translate the findings in mouse to human islets. There is a potent pharmacological compound – a Y1 inhibitor – that allows us to test with commercialisation potential. With an ADS Skip Martin Early Career Fellowship, I will now extend my recent published work with a detailed exploration of Y1 receptor inhibition in type 2 diabetes models. I aim to investigate whether pharmacological inhibition of Y1 receptor will enhance β-cell function and improve glucose homeostasis in type 2 diabetes.
How long before this work might impact clinical care?
While our research is still at a preliminary stage (ie in mouse models), we have at least tested our findings in human islets. We plan to perform more preclinical studies in the near future.
What’s your Holy Grail – the one thing you’d like to achieve in your research career?
Successfully discover at least one novel therapeutic target that ultimately leads to treatment for metabolic disorders such as diabetes and obesity.
What is your biggest research hurdle?
It’s very competitive and there is a lack of research funding opportunities for young scientists in Australia. However I’d like to thank the NHMRC, Diabetes Australia Research Trust and ADS for their support over the last five years.
Who has inspired you?
Professors Tony Tiganis (Peter MacCallum Cancer Centre), Herbert Herzog (Garvan Institute of Medical Research) and Bruce Kemp (St Vincent’s Institute) have provided me with their support and mentorship throughout my research career.