Researchers

My interests lie in the regulation of fat and carbohydrate metabolism in skeletal muscle, with a particular emphasis on the dysregulation that occurs in obesity and diabetes.  Several cytokines released from skeletal muscle, including leptin and adiponectin, are known to significantly affect insulin response in peripheral tissues such as muscle.  My research has focused on the effects of these adipokines on muscle lipid and carbohydrate metabolism, and particularly, how the muscle becomes resistant to their effects in obese models and with high fat feeding.  The interaction of diet and exercise is also a point of interest in terms of the muscle’s response to various hormones including insulin, leptin and adiponectin.

The general focus of my research program is the integration of diet and exercise in mediating metabolic processes in health and chronic disease.
I am interested in understanding the physiological roles and regulation of adipose tissue and skeletal muscle-derived cytokines in mediating metabolic processes in the body. I am particularly interested in the mechanisms by which dietary factors and/or exercise modulate various cytokines and inflammatory mediators implicated in insulin resistance, a key characteristic of obesity and type 2 diabetes.

Current Research Projects

• Regulation of adipose tissue-derived cytokines in integrative metabolism
• Effect of n-3 and n-6 fatty acids in the presence and absence of LPS on adipocyte secretory factors and underlying mechanisms
• Effect of dietary fatty acids on pro-inflammatory markers in an in vitro murine adipocyte macrophage co-culture model 

My research examines the structural and functional effects of aging on basic muscle contractile function; muscle mechanics and lengthening muscle actions; cross-bridge and non-cross-bridge based forces; history dependence of force production; age-related alterations to muscle mechanics, acute and chronic alterations to the​ neuromuscular system as a result of muscle fatigue, damage and natural aging; masters athletes and neuroprotective effects of exercise; muscle architecture plasticity and neural control of human movement.

Purposeful action requires the central nervous system to integrate, into ongoing movement patterns, available sensory information about body position in space. Vision is a unique sensory input as it provides this information in advance, for route-planning, and the adjustment of on-going stepping strategies. To date, my research program has focused on strategies used to execute safe movement during adapted locomotor tasks (steering, obstacle circumvention, obstacle stepping) and the role of vision in these tasks. 

I am also interested in exploring the impact of cognitive or brain function on locomotor control. The reality is, we routinely perform mental tasks while walking in busy, dynamic environments (e.g. listening to a loudspeaker announcement while walking through a busy shopping mall) and recent research indicates that performing more than one task at a time influences our walking performance. Given the commonness of dual tasking in our daily living, I hope to map patterns of cognitive-locomotor interference for multiple adapted locomotor (e.g. obstacle circumvention) and cognitive activities (e.g. visuo-spatial cognitive tasks) and ascertain optimal training strategies for dual-task performance.

It has been suggested that at different stages in life, there are varying levels of available cognitive resources in addition to shifts in the role of various sensory input in locomotor control, however, there is little basic scientific evidence which examines these shifts over the lifespan. 

For example, young children demonstrate effective locomotor strategies in uncluttered environments however observations during complex locomotor tasks e.g. obstacle avoidance tasks suggest that the maturation of locomotor control strategies are still developing in mid-childhood. In this area of my research program I probe how children perform cognitively demanding tasks while integrating sensory information during complex gait tasks.
At the other end of the life spectrum, my research program aims to explore how the aging process influences and changes the complex relationship between cognitive resources, sensory input and executed adaptive locomotor strategies. The increasing number of aging baby-boomers in Canada and the financial impact that falls in the elderly has on the healthcare system draws attention to the importance of this research focus.

Sensory contributions are intimately related to successful movement.  With age and pathology, there is an increase in the difficulties associated with mobility.  These changes alter the freedom and independence of the aging population and can largely be attributed to a decline in sensory function.  The primary goals of my research program are 1) to understand where posture is controlled 2) to understand what sensory information contributes to successful movement and equilibrium.

By investigating these two key questions I believe we will have a better understanding of how sensory decline contributes to a loss of mobility as we age.  Declines in sensory information are often replaced by other sensory modalities through compensation.  Does this take place at the level of the spinal cord, or further upstream with changes in cortical plasticity?  Are we able to develop facilitatory devices such as shoe insoles to improve cutaneous sensation or visual aids to enhance visual cues?

My research program involves two key areas of study.

• To perform direct recordings from sensory afferents and motor efferents in awake human subjects to investigate sensory contributions to movement, balance control, and reflex responses.
• To elicit balance perturbations to test the function of these reflex loops, and sensory contributions to the maintenance of equilibrium and postural control.

I use several techniques to investigate sensory contributions to standing balance.  To perturb the vestibular system I use the technique of Galvanic Vestibular Stimulation (GVS), which alters the firing of peripheral vestibular afferents and changes the perception of vertical.  One goal is to establish the role of vestibular input in “setting” the excitatory nature of the spinal cord.  In an altered vestibular state do we see changes in other sensory reflexes?  For example, does our ability to reflexively respond to a stumble change?

Microneurography is another technique used in my laboratory.  This tool enables direct recordings from afferent and efferent nerve fibres in awake humans.  The advantage of microneurography is that it enables a level of investigation currently unafforded by other approaches.  Our access to single cutaneous afferents, for example, allows us to monitor their involvement in postural responses, functional strategies and their interaction with other sensory input, including vestibular.  Many sensory receptors, such as those from the skin and muscle have been shown to degenerate with age and in certain pathological conditions.  My work to date has focused on determining how nerves connect in healthy individuals so that we can then apply this knowledge to developing rehabilitation programs for target populations.  Isolation of individual cutaneous receptors involved in functional postural responses will serve the purpose of developing more sophisticated and applicable prosthetic devices to facilitate skin input in deficient aged and diabetic populations.

Finally, I am able to examine contributions from cortical areas in the control of movement.  To do this I use a technique called transcranial magnetic stimulation (TMS).  TMS allows us to probe central contributions to postural reflex loops by enabling us to excite or inhibit descending input from the brain.

My overall research interest intersects the fields of clinical biomechanics and neurophysiology. I have a specific interest in the study of chronic pain and joint function associated with aging and chronic musculoskeletal diseases such as osteoarthritis, myofascial pain and fibromyalgia. A unique focus to my research is the study of the pathophysiologic mechanisms of myofascial trigger points, using both animal and human experimental models, and their role in the clinical expression and treatment of pain and joint/muscle dysfunction in chronic musculoskeletal disease.

A core theme of my research is the study of the neurophysiologic phenomenon known as central sensitization. Central sensitization is a neuradaptive state associated with chronic pain, however, the role of central sensitization in the physiologic expression of chronic myofascial pain and pathomechanics in chronic degenerative diseases such as osteoarthritis is poorly understood. My research aims to develop novel and/or enhance existing treatment approaches in clinical pain management (diagnosis and treatment) and musculoskeletal biomechanics/pathomechanics associated with chronic disease and aging.

My research interests are dedicated to understanding the mechanics and physiology of the lumbar spine and spine musculature.  This relates to four specific areas of study:

1. Function of the lumbar spine and spine muscles:
   • Understanding the anatomy of specific muscles and tissues of the spine, how they interact and are activated (muscles) and loaded (all tissues) to produce controlled movement
2. Injury to the lumbar spine and spine muscles:
   • Susceptibility under different loading scenarios
   • Types and mechanisms of injury
3. Adaptation of the lumbar spine and spine muscles:
   • Types of adaptations (to injury, changing internal or external environments)
   • Are the adaptations beneficial or detrimental?
4. Rehabilitation of the lumbar spine and spine muscles:
   • Can detrimental adaptations be reversed or corrected?
   • Strategies for rehabilitation

Studies in the lab generally follow one of three main paradigms:

1. Anatomical studies to characterize the mechanical capabilities of muscle and spine tissues:
   • Dissection and measurement of cadaveric human and animal tissues (eg. measurement of muscle physiological cross-sectional areas and sarcomere lengths to determine force generating and length changing capabilities, respectively) 
   • Modelling of functional capabilities based on these measurements
2. Mechanical testing of muscle and spine tissues:
   • Passive and active mechanical properties of different spine muscles
   • Mechanical interaction between neighbouring muscles and tissues
3. Testing of human participants to examine muscle activation (EMG), movement patterns and spine loading during a variety of tasks and perturbations:
   • Modelling muscle force generation, spine loading and stability

Information and insights obtained from the first two paradigms are used to feed into and out of the third paradigm, where the ultimate goal is to further the understanding of our four aforementioned “research themes”: human lumbar spine function, injury, adaptation and rehabilitation.

My research studies the regulation of genes involved in choline transport and phospholipid metabolism; nutrient transporters and kinetics of membrane transport; molecular and cell biology of lipids; the effect of nutrients on protein synthesis and gene expression. Nutritional genomics (nutrigenomics) of risk factors for cardiovascular disease and insulin resistance

Omega-3.  The focus of my research is to better understand how dietary fats influence health and disease throughout life with an emphasis on the prevention of chronic disease. Currently, a major area of study in my laboratory is the role of omega-3 fatty acids in breast cancer prevention.  We have shown that lifelong exposure to omega-3 fatty acids reduces mammary tumour development, which is mediated through changes in mammary gland development.  These findings provide evidence that omega-3 fatty acids are important components of the diet and play an important role in disease prevention.

Omega-6, trans, CLA, SAFA & MUFA.  I am also interested in the role of other bioactive fatty acids including omega-6 fatty acids, trans, conjugated linoleic acids, saturated and monounsaturated fatty acids in human health.  Other areas of research include brain health and Alzheimer’s disease, bone development, fatty liver disease and nutrigenomics.

Guelph Family Health Study.  In addition, as the Director of the Guelph Family Health Study (https://guelphfamilyhealthstudy.com), I lead a multidisciplinary team investigating determinants of health and interventions for the prevention of childhood obesity 

Training. As the lead applicant, I support a national network focused on Implementation Science training in Healthy Cities. Increasing urbanization creates opportunities and wicked challenges that require multidisciplinary and multisectoral approaches and interventions.  Training the next generation of leaders in implementation science will provide trainees the necessary skills and perspectives to tackle the problems of today and the future.  

Service.  In addition to my research responsibilities I serve on several committees and former President of the Canadian Nutrition Society.  I have served on CIHR and Cancer Research Society grant review panels, provided consultation for the food/fats & oils industry, and scientific leadership in the development of an unsaturated fat and cholesterol reduction health claim in Canada.

My research program focuses on the role of methyl nutrients in the risk of chronic diseases using precision nutrition approaches.  My laboratory uses animal models and human studies to provide mechanistic insights underlying metabolic disease risk from genetic, epigenetic, physiologic, metabolic and microbiome perspectives.  My research extends to the following core areas:

1. Role of methyl nutrients in metabolic programming of the epigenome and energy balance:  Inadequate or excess gestational consumption of nutrients can predispose the offspring to greater risk of metabolic diseases.  We have shown that an AIN-93G diet with high, non-toxic (10-fold) amount of multivitamins, methyl vitamins or folic acid alone consumed during pregnancy leads to the obesogenic phenotypes and epigenetic alterations in the hypothalamic regulatory systems in the offspring.  We utilize functional measures in addition to molecular analyses of genes, DNA methylation, proteins and hormones to elucidate mechanisms by which methyl nutrients shape epigenetic modification throughout the lifespan.
2. Diet, gut microbiome and genetic influences on trimethylamine-N-oxide (TMAO):  TMAO, the hepatic oxidized product of the gut microbial-derived trimethylamine is a newly emerged risk factor for cardiovascular disease.  We have previously shown that healthy young men with lower microbial diversity and greater enrichment of Firmicutes relative to Bacteroidetes exhibit a greater postprandial rise in circulating TMAO following dietary precursor consumption.  Unlike choline and carnitine, a methyl-deuterium-labeled TMAO metabolic tracer at physiologically relevant intake levels yielded near-complete absorption with uptake by extrahepatic tissue in a manner that appears to be under the influence of flavin-containing monooxygenase 3 G472A.  We continue to focus on individual variations of TMAO metabolism that may arise due to nutrient-gut microbiome-gene interactions using study designs that incorporate stable isotope methodology, 16S rRNA sequencing and SNP genotyping.

My research interests relate to relate to the biological effects of functional foods on chronic disease-related endpoints evaluated in human intervention studies, with a particular focus on the agri-food-health continuum.  Another research interest involves exploration of the use of functional foods and natural health products (prevalence, knowledge, attitudes) in healthy and clinical populations.

The mission of my laboratory is to help people get more from their body.  This applies across the spectrum of age and activity: from the elite athlete pursuing gains in performance to the person at risk of chronic disease seeking improvements in health.  We strive to accomplish this by gaining a better understanding of the physiological limits to optimal human body performance and the interactions with the physiological stressors of physical activity and exercise.

As such, my main research interests are thus split between two overlapping domains.  In the realm of human performance, we are investigating novel training methods, interventions and supplements which may lead to an acute or prolonged adaptation and performance improvement.  These include such things as blood flow restriction, training tools, and nutraceuticals.  In regard to health, our main interests surround the effects of physical activity, sport, and exercise to alter cardiovascular form and function (e.g. arterial stiffness, endothelial function) and metabolic regulation (glucose control) with a focus on the impact on chronic disease risk and management.

My main research focus centres around the issue of how contracting skeletal muscle can communicate with blood vessels in order to ensure adequate blood flow to the working skeletal muscle cells. There is a direct relationship between skeletal muscle metabolic rate and blood flow. This type of relationship requires that active skeletal muscle cells communicate their need for blood flow to the cells of the vasculature, endothelial cells and vascular smooth muscle cells, and that these cells alter their function in order to ensure the proper blood flow delivery. I am interested in this intercellular communication. The current thinking is that skeletal muscle cells release vasodilatory products which are end products of metabolism, and these products diffuse to effect the vasculature. Currently we are testing this hypothesis by contracting the skeletal muscle in various ways as to change its metabolism and determining how the different metabolic rates alter the microvasculature. We are also testing for what these specific diffusable products are and how they alter endothelial cell or vasculature smooth muscle cell function.

After working with Dr. Sarelius I have developed a keen general interest in the microvasculature of other tissue beds. This has lead to a variety of formal collaborations. I am part of a large NSERC/CIHR collaborative grant headed by Dr. Anne Croy at the Queens University where our part of the study is to characterize the nature of spiral artery function in pregnant females. Proper spiral artery function is necessary for healthy development and growth of the fetus as well as the health of the mother. Spiral artery dysfunction has been linked to pre-eclampsia and premature births. I also collaborate with Dr. Pat Wright in Zoology looking at the microcirculation of fish to understand how a certain species of fish can survive out of water for up to 30 days. So, basically, if it has a circulation I am interested in studying it!!!

I use classical physiology combined with proteomic techniques to study cardio-respiratory physiology and pathophysiology in multiple areas.

Heart failure remains the predominant cause of premature death and long-term morbidity in western society.  Cardiac hypertrophy (increase in cell size) develops in such conditions of chronic hemodynamic overload as hypertension and valvular disease.  Although the initial hypertrophy is critical as a compensatory response, it eventually becomes maladaptive, leading to contractile dysfunction and myocyte apoptosis.  Eventually, heart failure occurs.  Thus, a major goal of our lab is to better understand how the heart initially adapts to hypertension before the development of contractile dysfunction and heart failure.  We believe this will lead to a better understanding of why the heart begins to fail and will ultimately lead to new targets for the treatment of heart failure.

I am also interested in skeletal and cardiomyocyte cell signalling during normal and hypoxic conditions, both between the muscle cells and with other tissues in the body.  My research combines cell culture techniques with cutting edge proteomic tools to identify novel cardiac protein hormones.  I use different models to investigate their functional effects in vitro and in vivo.

While much is known about the development of exercise-induced fatigue of limb muscles, little is known about the proteomic alterations that occur during exercise that contribute to or compensate for contractile dysfunction.  Interestingly, we have recently shown that skeletal myofilament proteins undergo specific and progressive modifications during the development of muscle fatigue.  Current work is aimed at identifying key post-translational modifications of myofilament proteins that arise during the development of whole muscle dysfunction as a result of fatigue or ischemia and delineating their role(s) in contraction.  We have identified several key myofilament proteins that are altered in animal models but are potentially involved in the development of fatigue in humans.