Research Area: Mechanisms of disease

Lindsay Robinson

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. My current research projects are:
1) Regulation of adipose tissue-derived cytokines in integrative metabolism.
2) Effect of n-3 and n-6 fatty acids in the presence and absence of LPS on adipocyte secretory factors and underlying mechanisms.
3) Effect of dietary fatty acids on pro-inflammatory markers in an in vitro murine adipocyte macrophage co-culture model.

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Jeremy Simpson

My lab conducts research on several areas related to cardio-respiratory physiology and pathophysiology. For example, we are studying: 1) how the heart initially adapts to hypertension before the development of contractile dysfunction and heart failure; 2) skeletal and cardiomyocyte cell signalling during normal and hypoxic conditions; 3) proteomic alterations that occur in limb muscles during exercise; 4) key post-translational modifications of myofilament proteins that arise during the development of whole muscle dysfunction as a result of fatigue or ischemia; and, 5) dyastolic dysfunction in various physiological and pathological states, such as aging, sex differences, and models of heart failure.

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David Wright

Since changes in how the body metabolizes glucose are a hallmark of Type 2 diabetes, understanding how the function and metabolism of adipose tissue are regulated will be crucial for understanding diabetes itself. My students and I look at how exercise and nutritional interventions affect gene expression in adipose tissue, and, in turn, how these changes can affect both adipose tissue’s metabolism and the whole body’s glucose metabolism. One of the applications of my research is to potentially develop new, non-drug-based approaches that can be used to prevent and/or reverse Type 2 diabetes.

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Clara Cho

The primary goals of our research program include: 1) to determine the fundamental role of methyl nutrients in health outcomes; 2) to determine molecular mechanisms underlying the development of obesity, metabolic syndrome and chronic diseases; and, 3) to contribute to evidence-based strategies that will improve the health of the population.

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Dave Dyck

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.

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Graham Holloway

My research is primarily focused on understanding the regulation of mitochondrial bioenergetics, with a particular interest in studying fatty acid oxidation (breakdown of fat yielding energy) in skeletal and cardiac muscle. We also study human exercise performance as well as type 2 diabetes, heart failure, diabetic cardiomyopathy and various neuropathologies, all conditions that have been affiliated with alterations in mitochondria as a key event in the progression and/or development of the disease.

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Jen Monk

My students and I aim to understand the mechanistic role(s) of microbial-host intestinal communication. In particular, we focus on how microbial-derived metabolites (from dietary precursors) can influence the integrity of the colonic epithelial barrier (EB), as well as its capacity for defense and repair. The importance of this research lies on not only advancing basic knowledge on the effect of microbial metabolites on gastrointestinal functions, but also on informing the agri-food sector the ways in which the intake of nutrients, biomolecules, and dietary precursors can shape human health.

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Siavash Vahidi

A key focus of the group is on the protein degradation machinery that helps to maintain proper level of proteins (protein homeostasis) in Mycobacterium tuberculosis, the causative agent of TB, the world's single largest infectious killer that is annually responsible for 1.5 million deaths. The questions we aim to answer are:
1) What is the assembly mechanism of the M. tuberculosis proteasome core particle and its regulatory particles?
2) What is the role of allostery and long-range interactions in the machinery that tags substrates for proteasomal degradation?
3) How are substrates selected for tagging and degradation?
4) What is the molecular basis of antibiotics that operate by disrupting proteasomal protein degradation?

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Terry Van Raay

Many of the signaling pathways that are involved in development are also involved in the onset and progression of disease. As an example, the Wnt signaling pathway is required during many stages of development and in the homeostasis of stem cells in the adult. Perturbation of this pathway in stem cells in the adult often leads to cancer. It is now known that greater than 90% of colorectal cancers are caused by mutations in the Wnt signaling pathway. As this pathway is important for both proper development and disease, I am curious to know how this pathway can turn it self on and off so many times during development and why it fails to turn off in disease. The lab focuses on two negative feedback regulators of Wnt signaling: Nkd1 and Axin2.

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Chris Whitfield

Research in my laboratory is focused on the architecture and assembly of the cell surfaces of pathogenic bacteria. Current areas of emphasis are:
1) Structure and function of multi-enzyme complexes required for the export of capsular polysaccharides through the periplasm and across the outer membrane of Gram-negative bacteria.
2) Structural basis for substrate recognition by ABC transporters involved in the export of bacterial cell-surface polysaccharides.
3) Structure and function studies of prokaryotic glycosyltransferase enzymes.
4) Mechanisms that couple glycan biosynthesis and chain extension to transport pathways.

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Melanie Wills

My research group focuses on the diagnosis, prognosis and treatment of Lyme disease. I focus on different topics within this research theme, including: 1) the various forms that Borrelia (Lyme bacteria) can adopt and their corresponding role in the expression of the disease; 2) the effects of people and batceria genetics in the expression of of the disease; 3) the development of new diagnostic tools; and, 4) the interactions that people diagnosed with Lyme disease have with the medical system.

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Marica Bakovic

My background is in molecular and cell biology of lipid metabolism. Currently, my students and I work on the regulation of membrane phospholipids, fatty acids, and methyl-group donors. More specifically, we look at 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; and, nutritional genomics (nutrigenomics) of risk factors for cardiovascular disease and insulin resistance.

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Leah Bent

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. My research program involves two key areas of study:
1) 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.
2) To elicit balance perturbations to test the function of these reflex loops, and sensory contributions to the maintenance of equilibrium and postural control.

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Andrea Clark

More than 4 million Canadians have arthritis and the number of people living with arthritis continues to increase year after year. Osteoarthritis involves multiple tissues and often includes cartilage damage, bone sclerosis and synovial inflammation. A pressing need remains for joint localized therapies and interventions that could slow or ideally stop this debilitating disease.
In our research, we use genetic and surgical models of spontaneous osteoarthritis (with old age) and post-traumatic osteoarthritis (following injury). We follow the progression of disease in a joint in order to better understand how proteins such as TRPV4, integrin alpha1beta1 and cilia influence chondrocyte signal transduction and thus the development of osteoarthritis.

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Ray Lu

My lab focuses on two main axes of research:
1) Unfolded Protein Response and Human Diseases: We study proteins that play key roles in animal stress responses, specifically the Unfolded Protein Response (UPR), which has been linked to animal development, cell differentiation, as well as a variety of human diseases such as Alzheimer’s, diabetes, cancer and viral infection.
2) Molecular Mechanisms of Aging: We are working to establish planarians as a new aging model to test the hypothesis that longevity requires multiplex resistance to stress. We hope to identify genes or alleles that confer such multiplex stress resistance and/or promote longevity.

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Rod Merrill

My research is in the general area of protein structure and dynamics and is specifically focused on the biochemistry of bacterial toxins involved in disease and consists of the following projects: Membrane structure of the colicin E1 ion channel; data mining and bioinformatics of bacterial virulence factors; optical spectroscopic approaches to study protein structure and dynamics; enzyme reaction mechanism of the bacterial mono-ADP-ribosyltransferase family; inhibition mechanisms and structural complexes of toxins with inhibitors; and, X-ray structures of protein-protein complexes involving toxins.

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Mark Baker

My lab aims to understand 1) the molecular genetic mechanisms of recombination in mammalian cells; 2) how defects in recombination contribute to tumorigenesis; and, 3) the nature of recombination hotspots. We are presently researching questions pertaining to: the mechanism and frequency of recombination in mammalian cells; the role of large palindromes in promoting recombination; mammalian heteroduplex DNA formation and repair; genetics of strand invasion and 3' end polymerization; how DNA sequences act to stimulate recombination; non-crossover mechanisms of homologous recombination; the genetic control of recombination.

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Marc Coppolino

Cell adhesion and migration are fundamentally important to the existence of multicellular organisms. This is obvious in light of the numerous diseases that can afflict humans when these processes are impaired. Disruption of normal cellular adhesive and migratory activities can lead to developmental disorders and contribute to the progression of arthritis, immunological deficiencies and cancer. Both cell adhesion and migration are complex processes involving numerous biochemical signalling events, reorganization of the cellular cytoskeleton and localized remodelling of the plasma membrane. It is the goal of my laboratory to elucidate the molecular mechanisms that link these activities, allowing them to be coordinated during changes in cell adhesion and motility.

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Michael Emes

Much of our current effort is focused on understanding the regulation of starch synthesis in storage tissues such as the developing seeds of cereals. Starch is the major determinant of yield in such crops, and has wide application in both the food and non-food industries, yet there remain a huge number of unknowns in what limits the production and structure of this important glucan polymer. There is also an increasing realization that different types of starch provide benefits for human health. Our research covers cereals such as maize, barley, rice, and wheat, as well as the model organism Arabidopsis thaliana. I lead a large, interdisciplinary team whose expertise includes plant biochemistry, genetics, molecular biology, microbiology, human physiology, and nutrition.

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Nina Jones

Research in our laboratory is focused on defining eukaryotic signal transduction pathways, and investigating how mutations in components of these pathways can contribute to human disease. Signal transduction is a central process in multicellular organisms that allows for the exchange of informational cues between and within cells. Current areas of research include: 1) Signalling pathways controlling kidney podocyte morphology; 2) focal adhesion dynamics in cancer cells; and, 3) characterization of a novel neuronal adaptor protein, ShcD.

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Shaun Sanders

The Sanders lab is interested in how neurons use the protein-lipid modification palmitoylation to target proteins to subcellular locations and to define how palmitoylation-dependent targeting contributes to physiological neuronal function and neuropathological conditions. Current projects include characterizing how palmitoylation of vesicular transport machinery regulates fast axonal transport and how palmitoylation of ion channels and their scaffold proteins regulates clustering at the axon initial segment, a critical site of neuronal excitability where action potentials are generated.

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John Srbely

My research program adopts a broad and integrative approach to the study of chronic musculoskeletal pain, incorporating both basic and clinical sciences. A major arm to my research program is investigating the underlying pathophysiologic mechanisms using both animal and human models. My research also aims to advance reliable diagnostic criteria (imaging, biomarkers) and physical assessment techniques (quantitative sensory testing, electromyography) that enable effective and reliable treatment and management strategies. By emphasizing transdisciplinary and multi-institutional collaborations, my research program will continue to inform future clinical and experimental initiatives in the field of chronic musculoskeletal pain.

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Jasmin Lalonde

The growth of neurons and their organization into circuits is a tightly controlled process that follows a series of well-defined steps. Once differentiated and integrated into networks, neurons also retain a remarkable capacity to rapidly change the arrangement of their connections in response to activity, a feature that is believed to critically support cognition as well as our ability to learn and retain information for long periods of time. Accumulating evidence strongly suggests that perturbation of the molecular interactions responsible for the growth of neurons, or the capacity of these cells to adequately respond to activity-dependent signals, contributes to the pathophysiology of different brain disorders. Our laboratory uses a multidisciplinary approach to explore these questions.

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Scott Ryan

While animal models have lead to huge advancements in our understanding of neurobiology, there is controversy over whether overexpression/silencing of gene expression is representative of diverse disease states. Indeed, the lack of availability of primary human neurons has made evaluating the pathological consequences of genomic mutations arduous. The use of human induced pluripotent stem cell (hiPSC) technology overcomes these limitations by providing a source of human neurons from both normal and disease genetic backgrounds. We currently focus on stem cell based models of Parkinson's Disease (PD) to study how mitochondrial stress mechanisms impact on neuronal function in human disease.

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Emma Allen-Vercoe

We currently have several projects in various areas that explore aspects of the gut microbiome and beyond:
1) Understanding how gut microbes are involved in the modulation of disease in colorectal cancer, diabetes, infection, and inflammatory bowel diseases
2) Isolation and characterisation of hunter-gatherer people's gut microbiome in an effort to discover novel microbial species and understand their function
3) Characterisation of the non-bacterial microbes of the human microbiome and their functions
4) Building model systems to study human gut microbes in vitro and in vivo
5) The study of 'oncomicrobes' (in particular, Fusobacterium nucleatum), and the development of colorectal cancer.
6) Translation to the clinic - development of 'microbial ecosystem therapeutics'

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