Education:

• 2006-2008 - Post-Doc. (Physiology) Faculty of Medicine, University of Manitoba
• 2003-2007 - Ph.D. (Work Physiology) Faculty of Kinesiology, University of Waterloo
• 2000-2002 - M.Sc. (Work Physiology) Faculty of Kinesiology, University of Waterloo
• 1996-2000 - B.Sc. (Kinesiology) Faculty of Kinesiology, University of Waterloo

Research Group Affiliations

• Human Leisure Health and Performance (HLHP) Research Institute, University of Manitoba, Winnipeg, MB, Canada
• Institute of Cardiovascular Sciences (ICS), St. Boniface Hospital Research Centre, Winnipeg, MB, Canada

Research Focus Creating a link between Kinesiology and the Cardiac Sciences

Heart disease is the leading cause of death amongst diabetic populations. In fact, epidemiological studies have estimated that greater than 6% of the population has diabetes. However, diabetics represent as much as 25% of the population diagnosed with cardiac dysfunction. More notably, 4 out of every 5 deaths in diabetic populations are attributed to cardiovascular diseases. One factor contributing to the high incidence of heart disease in this population is the fact that diabetes promotes the pathological remodeling of cardiac proteins at the level of the cardiomyocyte (the contractile cell in the heart), which impairs the ability of the heart to pump blood effectively (commonly referred to as diabetic cardiomyopathy). The contractile dysfunction that characterizes diabetic cardiomyopathy has been shown to be directly influenced by abnormal ryanodine receptor (RyR2) and sarcoplasmic reticulum calcium-ATPase (SERCA2a)-mediated calcium cycling. Therefore, it is imperative that researchers identify therapeutic approaches to restore or enhance the expression and function of RyR2 and SERCA2a proteins in the diabetic heart.

Sufficient physical activity is a prerequisite for health. In fact, physical activity is widely accepted as a pillar for the prevention of Type 2 diabetes, as people that are insufficiently physically active (i.e.; those who lead a sedentary lifestyle) are at an increased risk of developing Type 2 diabetes compared to individuals who engage in regular physical activity. Even so, we still do not fully understand the biological mechanisms to explain how physical activity facilitates health. Part of the reason for this deficiency is that we still have not defined the minimum or optimal doses of physical activity required to maintain health. Several studies have indicated that the beneficial effects of regular physical activity may depend on the intensity and volume of exercise performed. However, controversies associated with the clinical feasibility of moderate and high intensity exercise training protocols still exist. Specifically, there is concern that high intensity exercise protocols may not be appropriate for heart disease patients because this population tends to have reduced aerobic fitness and impaired cardiac function compared to healthy individuals. Therefore, one of the objectives of my research program is to characterize the potential health benefits of two clinically relevant physical activity interventions. One intervention will employ a voluntary exercise model where participants individually select the intensity, duration and frequency of physical activity completed. The second intervention will employ a prescribed high-intensity interval running model where participants will run on a treadmill for 1 hour per day, 5 days per week using an intermittent interval running program where they perform interval training intervals of 2 minutes at 85-90% of their aerobic fitness level followed by 2 minutes at 40-50% of their aerobic fitness level. These interventions are similar to the voluntary walking programs or prescribed exercise interventions being utilized to reduce the prevalence of heart disease and Type 2 diabetes in a variety of research settings. Our rationale for including both physical activity interventions is to directly compare the potential clinical benefits of each approach by determining if these physical activity models improve cardiovascular health differently or more effectively than the other approach.

I envision a research program that will combine experimental research with clinical initiatives. Therefore, I will utilize isolated cell models, animal models as well as human volunteers to conduct this physical activity-based research program. My basic science program will focus particular attention to identify the cellular and molecular processes that regulate muscle metabolism and calcium transport proteins during a single bout of physical activity or in response to physical activity training.

Exercise physiology

It is now widely accepted that exercise training prevents heart disease and counteracts many of the disease processes that contribute to heart disease. One of the reasons for this health benefit is that exercise-training normalizes myocardial calcium-cycling by restoring RyR2-mediated calcium-release and SERCA2a protein expression in the diabetic heart. Furthermore, our preliminary work in this field indicates that the beneficial effects of exercise-training are dose-dependent. However, previous work in this area, including our own, has not identified the underlying biological mechanisms by which exercise regulates RyR2 and SERCA2a protein expression and function in the diabetic heart. Therefore, a significant opportunity exists to utilize physical activity as a tool to identify novel therapeutic targets and signaling pathways that regulate heart health. Accordingly, my research program will take advantage of this opportunity to establish a causal relationship between proteins that are turned on/off by exercise training and the regulation of RyR2 and SERCA2 protein expression and function. To do so, we plan to conduct gain and loss of function experiments using adenovirus-mediated gene overexpression to selectively manipulate target protein content in primary cardiomyocytes isolated from wild-type or transgenic mice. We also utilize treadmill-based or voluntary wheel running interventions to manipulate target protein content and activity in vivo. Collectively, these approaches will enable us to identify novel biological pathways that regulate RyR2 and SERCA2a protein expression and function in the diabetic heart, which may serve as the theoretical basis to guide the development of novel therapeutic interventions to prevent or better manage the clinical complications of diabetic cardiomyopathy.

Clinical exercise physiology

My clinical research program examines the utilization of clinical exercise rehabilitation programs for the prevention or treatment of diabetes and cardiovascular disease. To facilitate this clinical research program, I have created links with regional cardiac rehabilitation programs at the Reh-Fit Center and the Wellness Institute at Seven Oaks Hospital. My research program directly interacts with the Cardiovascular Health and Research in Manitoba (CHaRM) Investigator group. This group was created to improve the care and quality of life of patients with cardiovascular disease through multi-disciplinary, investigator-initiated research and to promote the collaboration for basic, translational and clinical research in Manitoba. This inter-professional research group draws expertise from several disciplines in the field of cardiac sciences, including cardiac surgery, cardiology, nursing, pharmacy, cardiac rehabilitation and epidemiology. For example, we have worked on a prospective, observational trial at the St. Boniface General Hospital examining the Impact of Physical Activity on Depression after Cardiac Surgery (IPAD-CS).

Although there is a widespread recognition that people who are active have a reduced risk for chronic disease, traditional primary care services in Canada do not provide the supports patients require to adopt a more physically active lifestyle. To address this gap, we have partnered with the Winnipeg Regional Health Authority to conduct research examining the implementation of a model for physical activity promotion within primary health care. Specifically, the ENCOURAGE project will integrate a kinesiologist into an existing Winnipeg Regional Health Authority primary care team to determine if this addition will enhance the prescription of physical activity as a health intervention. The kinesiologist’s role will be to support and educate the primary care team about the link between physical activity and patient care. The kinesiologist will also develop patient-centered referral processes so patients can access existing physical activity programs through new linkages between primary care and community-based physical activity providers.

By collaborating with others researchers and partnering with service providers in the community, my clinical research program will be positioned at a point where it can create knew knowledge and then translate that knowledge into programs that will improve cardiovascular health in society.

Why is this work important?

Physical activity is viewed as a viable approach for the prevention and treatment of many chronic diseases, including cardiovascular disease, type-2 diabetes, and some cancers. Insufficient physical activity is the single largest risk factor contributing to development of chronic diseases in the world today. For example, epidemiological studies have indicated that less than 15% of Canadians are physically active enough to maintain optimal health. A greater concern for the health of Manitoban’s, is the fact that less than 10% of our children meet current physical activity guidelines. If this trend continues, it is expected that 1/3rd of our children will develop type 2 diabetes by the time they reach 20 years of age. This should concern parents as diabetics tend to have a life-expectancy that is ~7 years shorter than non-diabetic populations. Diabetes is also a major risk factor for the development of many cardiovascular diseases, which could be expected to further reduce the life expectancy of our children as cardiovascular diseases tend to develop much earlier in diabetic patients compared to the general population. Physical inactivity is also a major concern for the health care system, as health care expenditures associated with diabetes exceed $13 billion per year.

Historically, society has viewed physical activity as a leisure activity, a work (labor) activity or a sports-associated endeavor. However, there is a paradigm shift occurring in the world today, which is leading to the view that there is a minimum amount of physical activity required to maintain health. In fact, there is a compelling amount of data to suggest that insufficient physical activity induces genetic changes, which promote the development of chronic diseases and lead to the manifestation of pathological symptoms, by activating “disease-promoting” genes and by inhibiting “health-promoting” genes. Conversely, there is a growing body of evidence indicating that regular physical activity reduces the impact of chronic diseases, such as cardiovascular disease, type-2 diabetes, and some cancers, by activating “health-promoting” genes and by inhibiting “disease-promoting” genes.

What techniques and equipment are used in this laboratory?

My basic science program employs a range of animal models of Type 1 diabetes (streptozotocin induced Type 1 diabetes), dietary induced insulin-insensitivity (high western fat feeding, sucrose feeding), as well as genetic models of type 2 diabetes (ob/ob mice or db/db mice). The physical activity models that we employ for our animals studies are based on two clinically relevant physical activity interventions (8 weeks in duration). The first intervention will utilize spontaneous wheel running, where animals individually select the intensity, duration and frequency of physical activity completed. The second intervention will utilize prescribed high-intensity interval running, where rats will run on a treadmill for 1 hour per day, 5 days per week using an interval running program where they complete a 10 minute warm-up run at 50% of their aerobic fitness level followed by 5 intervals of 8 minutes at 85-90% of their aerobic fitness level followed by 2 minutes at 60-65% of their aerobic fitness level. It should be indicated that this physical activity pattern simulates the activity patterns that many animal voluntarily choose to do every day. Moreover, these interventions are similar to the voluntary walking programs or prescribed exercise interventions being utilized to reduce the prevalence of T2Dm in society. To analyze tissue samples, we utilize several biochemical, cellular and molecular assessment techniques in our laboratory to examine the changes that occur in response to models of physical inactivity, physical activity in combination with our chronic disease models. We also assess functional changes in muscle and cardiac contractility through the use of echocardiography technologies, miniature catheterization technologies, and isolated tissue (cell culture and isolated muscle) technologies. Our laboratory also has access to equipment that can detect and analyze proteins (Western blot) and RNA (real-time PCR). Fluorescent, spectrophotometric and radioactive assays can be employed to characterize changes in protein function in tissue homogenates and isolated fractions.

Our clinical research program also uses a variety of tools. For example, we use two approaches to assess changes in physical activity behaviour, including the use of the International Physical Activity Questionnaire (IPAQ) and Actical accelerometers. We also use surveys to assess measures of anxiety and symptoms of depression using the Cardiac Anxiety Questionnaire (CAQ) and the Patient Health Questionnaire (PHQ-9), respectively. Finally, we assess clinical outcomes by reviewing patient medical records to determine if the specific interventions lead to changes in blood pressure, blood lipids and other parameters routinely collected by primary care physicians.

Dr. Todd Duhamel

Dr. Todd Duhamel was born in Atikokan, Ontario. After completing his undergraduate degree in Kinesiology at the University of Waterloo, he went on to complete a Ph.D. in the field of skeletal muscle physiology in the laboratory of Dr. Howard Green at the University of Waterloo. To complete his academic training, he finished a 2 year postdoctoral fellowship placement within the Institute of Cardiovascular Science at the St. Boniface General Hospital Research Centre. Dr. Duhamel is a recently recruited Assistant Professor in the Faculty of Kinesiology and Recreation Management, University of Manitoba. His research program brings a distinct expertise to the Institute of Cardiovascular Sciences, as he has a particular research emphasis examining the role of physical activity for the prevention, as well as treatment of cardiovascular disease in diabetes.

For more information, please contact:

Dr. Todd Duhamel
Tel. 204.235.3589
Email. tduhamel@sbrc.ca

Articles Published in Refereed Journals

1. Hnatiuk JA, Duhamel TA, Katz A, Ready AE.Physical Activity Supports Provided by Health Care Providers to Patients with Type 2 Diabetes. Canadian Journal of Diabetes. Accepted. In press. 2012.

2. Green HJ, Duhamel TA, Smith IC, Rich SM, Thomas MM, Ouyang J, Yau JE. Muscle Fatigue and Excitation-Contraction Coupling Responses Following a Session of Prolonged Cycling. Acta Physiol (Oxf). 203(4):441-55. doi: 10.1111/j.1748-1716.2011.02335.x. 2011.

3. Green HJ, Duhamel TA, Smith IC, Rich SM, Thomas MM, Ouyang J, Yau JE. Muscle metabolic, enzymatic and transporter responses to a session of prolonged cycling. Eur J Appl Physiol. 111(5):827-37. 2011.

4. Bohm CJ, Ho J and Duhamel TA. Regular physical activity and exercise therapy in end-stage renal disease: how should we move forward? J Nephrol. 23(3):235-43. 2010.

5. Adameova A, Xu YJ, Duhamel TA, Tappia PS, Shan L, Dhalla NS. Anti-atherosclerotic Molecules Targeting Oxidative Stress and Inflammation. Curr Pharm Design 15: 3094-3107. 2009.

6. Green HJ, Bombardier E, Duhamel TA, Stewart RD, Tupling AR, and Ouyang J. Metabolic, enzymatic and transporter responses in human muscle during consecutive days of exercise and recovery. Am J Physiol Regul Integr Comp Physiol. 295(4):R1238-50.2008.

7. Dhalla NS, Sani-Chohan HK, and Duhamel TA. Strategies for the regulation of intracellular calcium in ischemic heart disease. Future Cardiology. 4(4), 339-345. 2008.

8. Green HJ, Duhamel TA, Stewart RD, Tupling AR, and Ouyang J. Dissociation between changes in muscle Na+-K+-ATPase isoform abundance and activity with consecutive days of exercise and recovery. Am J Physiol: Endo Metab. 294(4):E761-7. 2008.

9. Green HJ, Duhamel TA, Holloway GP, Moule J, Ranney DW, Tupling AR and Ouyang J. Rapid upregulation of GLUT4 and MCT4 expression during sixteen hours of heavy intermittent cycle exercise. Am J Physiol Regul, Integ Comp Physiol. 294(2):R594-600. 2008.

10. Duhamel TA and Dhalla NS. New insights into the causes of heart failure. Drug Discov Today: Dis Mech 4: 175-184, 2007.

11. Duhamel TA, Green HJ, Stewart RD, Foley KP, Smith IC, and Ouyang J. Muscle metabolic, sarcoplasmic reticulum calcium cycling and blood hormonal responses to prolonged cycling with and without glucose supplementation. J. Appl. Physiol. 103(6):1986-98. 2007.

12. Duhamel TA, Stewart RD, Tupling AR, Ouyang J, Green HJ. Muscle sarcoplasmic reticulum calcium regulation in humans during consecutive days of exercise and recovery. J Appl. Physiol. 103(4):1212-20. 2007.

Funding

Opportunities

My research program is currently accepting applications for students with an interest to pursue graduate degrees, research projects or summer research opportunities. I strongly encourage interested candidates to contact me to pursue these opportunities.