Q&A with Amanda Greenwell

For her excellence in research on working to validate a potential new drug class for diabetes, Faculty of Pharmacy and Pharmaceutical Sciences doctoral student, Amanda Greenwell, has received both the Vanier Canada Graduate Scholarship and Izaak Walton Killam Memorial Scholarship.

Amanda Greenwell (BSc 2018, PhD 2024) has always been fascinated by the heart. She graduated with a Bachelor of Science in Biological Sciences from the University of Alberta in 2018, during which she met her current supervisor, Dr. John Ussher, Associate Professor and Canada Research Chair in Pharmacotherapy of Energy Metabolism in Obesity, when he taught several lectures in an undergraduate cardiovascular physiology course. From there, she joined the Faculty of Pharmacy and Pharmaceutical Sciences to pursue her PhD in Pharmaceutical Sciences under his supervision.

Recently, Greenwell was awarded the Vanier Canada Graduate Scholarship, one of Canada’s most prestigious awards for doctoral students that demonstrate both leadership skills and a high standard of scholarly achievement, and the Izaak Walton Killam Memorial Scholarship, the most prestigious graduate award administered by the University of Alberta, for her excellence in research on diabetes—a disease defined by high blood sugar that affects 463 million people globally—particularly, working to validate a potential new drug class for diabetes that is safe for the heart. 

What research are you working on now?

Individuals with diabetes are at a significant risk of developing heart disease. The risk for heart failure can be increased up to two-fold in males and up to five-fold in females. Given the strong link between diabetes and heart disease, health agencies (e.g. Health Canada) now require that all drugs in development for diabetes undergo rigorous testing to determine their impact on heart health. Recently, the Ussher lab has discovered that a clinically available drug for treating Tourette’s syndrome, pimozide, improves blood sugar control in diabetic animals by preventing the body’s muscle from burning ketone bodies, a fuel source produced from fats by the liver, for energy. Although the link between ketone body metabolism and blood sugar control requires further investigation, pimozide and more broadly, inhibition of ketone body metabolism, represents an exciting new class of drugs for the treatment of diabetes provided that it is deemed safe for the heart. Therefore, the goal of my research will be to study the effects of inhibiting the heart’s reliance on ketone bodies for energy in order to validate its potential as a new drug class for diabetes. 

What do you hope to accomplish in your research?

Therapies specifically designed to treat diabetes-related heart disease are limited, thus there is a critical demand for anti-diabetic treatments that also improve cardiovascular outcomes. Although the exact cause of diabetes-related heart disease is unknown, there is evidence that the heart of a diabetic individual is unable to produce enough energy to effectively pump blood throughout the body and relax between beats. Specifically, the ability of the heart affected by diabetes to use sugar for energy is reduced.  Furthermore, several studies have reported that ketone body metabolism is also altered in the diabetes-affected heart, however, whether this alteration reflects a helpful or harmful response remains unknown. Therefore, with my research, we hope to shed further light on the role of ketone body metabolism in the development of diabetes-related heart disease and whether pharmacological manipulation of the pathway represents a potential therapeutic target. Our previous data suggests that pimozide improves blood sugar control in diabetes by increasing sugar metabolism in the muscle. Interventions that increase heart sugar metabolism also improve heart function in animal models of diabetes. Therefore, inhibition of ketone body metabolism could have heart protective effects in the context of diabetes. Ketone bodies also have potent anti-inflammatory properties, thus ketone body accumulation in the heart as a result of inhibited usage for energy could reduce the high level of inflammation that is characteristic of the heart affected by diabetes.

Why did you choose this area of research?

I have always been fascinated by the heart. I actually met my supervisor, Dr. John Ussher, when he came to teach several lectures in an undergraduate cardiovascular physiology course. However, I fell into diabetes research quite unexpectedly. When I initially joined Dr. Ussher’s lab as a Master’s student in 2018, my work was predominantly focussed on investigating the alterations in energy metabolism that may contribute to heart dysfunction in the rare genetic disorder, Barth Syndrome. After having the opportunity to work on several diabetes-related projects in the lab, the field really captured my interest, so when the opportunity to work on diabetes-related heart disease came up, I knew that this was the perfect thesis project for me. Although the main focus of my research will be to investigate cardiac energy metabolism in the context of diabetes, I am also continuing my research in Barth Syndrome and leading projects to determine the effect of the ketogenic diet on cardiac function and glycemic control in obesity. I am very grateful to be in a lab that allows me to explore my diverse research interests. I believe that the diversity of my research portfolio allows me to approach my projects with a more well-rounded and comprehensive perspective, in addition to keeping research continually exciting and engaging.   

Why is your work important to you?

The prevalence of diabetes has reached an epidemic level affecting nearly 463 million people worldwide and heart disease represents the leading cause of death among those affected by the disease. Interestingly, even when blood sugar levels are well controlled, diabetic individuals are still at an increased risk for heart disease. This highlights the critical need for further investigation into the factors underlying diabetes-related heart disease in order to improve its clinical management. It is extremely motivating knowing that I have the opportunity to work in an area that has the potential to improve the quality of life of so many people.    

How does it feel to be the recipient of the Vanier Canada Graduate Scholarship and Izaak Walton Killam Memorial Scholarship?

I feel incredibly honoured to be a recipient of the Vanier and Killam Scholarships. Graduate school has definitely helped me to achieve a much greater sense of clarity regarding my interests and goals and has opened my eyes to opportunities and careers that I had never previously considered. To receive these scholarships was exceptionally encouraging as it was reassuring to know that I am on the right path, plus it affirmed the enthusiasm for the work we are doing. In my spare time, I coach an incredible group of girls in rhythmic gymnastics. With these awards, I hope to inspire an enthusiasm for science in the young women I teach and to empower them to always follow their passions and dreams. 

What are your goals and aspirations for the future?

After I complete my PhD, I plan to pursue an MD with the eventual goal of becoming a clinician-scientist in the field of pediatric cardiology. I would love to establish my own independent research program at an academic medical centre and be involved in the facilitation of a translational research education program. 

What's your favourite thing about studying at the University of Alberta?

Being able to work with such an incredible and talented group of people is definitely my favourite part about conducting research in the Faculty of Pharmacy and Pharmaceutical Sciences. I am really grateful for all the extraordinary support, encouragement and advice that I have received from my supervisor, mentors and colleagues.