July 03, 2020 Getting to the heart of the matter: A Q&A with one of our researchers

Dr. Thomas Pulinilkunnil and his team of researchers are examining if high blood glucose and fat levels cause the lysosomes (the “garbage cans”) of heart cells to stop working, allowing too much “junk” to build up in the cells and damage them. His research team will examine how lysosomes fail, if this is the cause of heart failure in diabetes, and if preventing this damage could reverse heart disease in people with obesity and diabetes.

Why did you choose diabetes and/or become a researcher?

My parents and their siblings have diabetes. I have personally seen the impact of this disease, which fuelled my desire to pursue diabetes research. This disease affects many systems in the body (eyes, skin, nerves), but the primary reason people die from diabetes is due to complications of the heart. In fact, many of my close and extended family members with chronic diabetes have developed heart disease.

How has the COVID-19 pandemic impacted your current research work? Can you describe a typical day in your lab? (pre- and post-COVID-19, if it has changed)

Due to COVID-19 all obesity and diabetes research-related activities in the university were suspended in the last week of March. We will commence research operations from July 1, only allowing 25 per cent of the research workforce to return to laboratory work to adhere to safe distancing guidelines.

A typical day pre-COVID-19 would encompass teaching, supervisory duties, meeting with research staff and trainees, discussing science, attending seminars, working in the laboratory, meeting students and offering them career support and guidance, and interacting with collaborators.

COVID-19 has disrupted research productivity and compelled researchers to move a few of these activities online. Despite pandemic times—wherein I primarily worked from home and tended to my five-year-old (I say “at home trying to work”)—I was able to maintain consistent contact with my research staff and trainees. We increased virtual engagement by actively participating in Zoom webinars/seminars to keep up to date with novel findings in the realm of diabetic heart disease. I do miss the coffee and lunch breaks with my research team and lab gatherings during which we actively discussed science and rewarded the hard work of our research staff and trainees. I must say that COVID-19 could not dent our research resilience, perseverance and zeal to garner knowledge and help individuals with diabetic heart disease. We will be back in the lab soon and hope for the best.

How did you come up with/settle on your research topic - Lysosomal role of transcription factor EB in diabetic cardiomyopathy?

The longstanding view that disordered metabolism of glucose and fatty acids in the power house of cells (mitochondria) is necessary and sufficient for causing heart failure is now being challenged by newer studies emphasizing the importance of cellular garbage cans, or lysosomes, in mediating heart dysfunction. Cellular waste degradation by lysosome is important to most disease states but its role in obesity and diabetes has not been well investigated. Our research investigates the link between how improper glucose and fat metabolism damage the garbage cans of the cell to hamper waste degradation. There are few labs in Canada which examines the impact of nutrient metabolism on lysosomal function in cardiac health and disease. Therefore, understanding the process of lysosome dysfunction in diabetic heart disease became a clinically relevant area of investigation of my laboratory.

Can you explain your research and its importance for people living with or impacted by diabetes? OR What’s the goal of your research and why does it matter for people living with or affected by diabetes? Can you explain the process of your research and any published preliminary results or findings?

If insulin is working properly, then glucose [sugar] can get into the heart for being used as energy. When insulin doesn’t work properly during obesity or when insulin levels are not adequate enough during diabetes, the heart is unable to use glucose and starts borrowing fat for use as energy source. Researchers have determined that [excessive dependence on fat for energy, rather than glucose,] is contributing to heart complications in people with diabetes. [One of the problems is] the failure of lysosomes—the heart cells’ ‘garbage cans.’ We discovered that, in people with diabetes, the heart accumulates more ‘garbage’ because the [lysosomes] do not work as well as they should, which makes the heart cells less efficient over time until the cells die. This eventually leads to heart failure.

If there’s one thing you could tell us about your research, what would it be? What would you want a person living with type 1 or type 2 diabetes to know about your research study and its potential impact?

The risk of heart disease and hypertension (high blood pressure) is increased three to four-fold in obese and diabetic patients, resulting in poor quality of life and premature mortality. Since current drug therapies can’t effectively control high blood glucose and excess fat, patients are exposed to the toxic effects of both, which also expose the heart to numerous complications.

Studies from Pulinilkunnil laboratory will provide insight into how maintaining lysosomal function is vital to prevent obesity and diabetes-induced cardiovascular injury. We welcome your continued support for our research program, which will help us to develop more targeted treatments that have a positive impact on the heart health of patients living with obesity and diabetes.

Why is it important for organizations like Diabetes Canada to fund a variety of research strategies such as complications and treatments?

The prevalence of diabetes in Canada is between 5-7 per cent, with the number of patients expected to almost double over the next 10 years, given the high incidence of obesity—a common risk factor for type 2 diabetes. In patients with obesity and diabetes, fat metabolism damages cellular structure and communication, predisposing the heart to premature failure when associated with comorbidities, such as high cholesterol, hardening of the arteries, and high blood pressure. Elucidating the specific mechanistic link between metabolic changes and lysosomal function during obesity and diabetes will result in novel and effective therapies aimed at preserving cardiac function and reducing the risk of heart failure, which is clearly relevant to the mission of Diabetes Canada. Diabetes Canada made it possible for me to pursue my research career mission to advance the scientific knowledge of how diet, genetics and environment unite to alter heart function in obesity and diabetes, which influences outcomes of cardiovascular complications, and is the major reason for mortality in our aging Canadian population. My future goal is to identify, design and implement translational research strategies to improve the heart health of Canadians.

Could you describe the impact of the Diabetes Canada funding, in terms of the subsequent funds you were able to secure as a result of your work?

Research in Pulinilkunnil laboratory is expected to lead to the development of new therapies that could limit and rescue heart failure, and provide relief to patients from the devastating effects of obesity and diabetes. With support from Diabetes Canada we recruited highly qualified personnel, communicated and disseminated our scientific results and leveraged funding with funding from agencies like Canada Foundation for Innovation, Natural Sciences Engineering Research Council, New Brunswick Health Research Foundation, and Dalhousie Medical Research Foundations to conduct patient-oriented research.