Research Area: Mechanisms of disease

Angela Scott

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Overall, my research program takes an integrative and comparative approach to study glial-neuronal interactions in relation to early development, physical injury, and neurological disease that spans across multiple levels of biological organization (molecular and cellular physiology > systems biology) and multiple model species (zebrafish and mice).
Our two areas of focus are:
1) investigation of glial-mediated mechanisms underlying development and disease;
2) exploration of naturally adaptive models with significant recovery from, or tolerance to, neurological stress or disease.

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Robert Harkness

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The Harkness group studies the dynamics of biological molecules toward better understanding how these influence human health and disease. Broadly, our areas of interest include:
(1) How biological macromolecules self-assemble, for example oligomeric protein “machines” that perform reactions as required by the cell, or non-canonical nucleic acid structures such as G-quadruplexes that regulate gene expression.
(2) The mechanisms of biomolecular recognition, e.g. allostery in modulation of the interactions between proteins and ligands.
(3) The relationship between structural dynamics and biological activity.

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Priyanka Pundir

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We study how eukaryotic cells communicate with microorganisms, focusing on cell surface receptors and their interaction with host and microbe ligands. We work at the intersection of immunology, microbiology, and neurobiology on how G protein-coupled receptors (GPCRs) on mast cells detect interbacterial communication and trigger antibacterial immune defense. We have shown that GPCRs can detect bacterial quorum sensing molecules, which are used by bacteria to coordinate group behaviors like forming biofilms and developing antibiotic resistance. When mast cells detect these signals, they release anti-bacterial mediators that attract other immune cells to sites of infection. Our ultimate goal is to advance knowledge that can lead to new treatments for infectious and inflammatory diseases.

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Melanie Alpaugh

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The Alpaugh Lab studies the mechanisms and consequences of protein misfolding in neurodegenerative diseases.
Theme 1- Interactions between the blood-brain barrier and misfolded proteins. Protein accumulation and blood-brain barrier break down are common features of diseases such as Alzheimer’s, Parkinson’s and Huntington’s diseases. We aim to understand if these two common disease features are related using a human 3D-cell culture model of the blood-brain barrier and human tissue.
Theme 2- Contributions of huntingtin seeding and spreading to Huntington’s disease. The mutant huntingtin protein displays prion-like properties. The Alpaugh lab is tackling the relevance to Huntington’s disease using tissue from human patients with Huntington’s disease phenocopies and Huntington’s disease.

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Matthew Sorbara

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Healthy gut microbiota can be disrupted due to antibiotic treatment, intestinal inflammation, or changes in diet. Targeted restoration of the microbiota will require an understanding of how genomic diversity between closely related microbes influences their ability to drive beneficial functions. To address this, our laboratory will use a large collection of whole-genome sequenced isolates to understand how variation between closely related gut isolates alters their ability to prevent pathogen expansion and maintain homeostatic interactions with the mucosal immune system.

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Sherri Cox

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My research is rooted in wildlife rehabilitation. Specifically, I am interested in the welfare of wild animals and helping restore health to sick and injured wildlife. I am also interested in looking at anthropogenic effects on wildlife that have been admitted to rehabilitation centres. There are so many ways that our actions have an impact on wildlife, and I am interested in helping wildlife rehabilitators care for wild animals for subsequent release back to the wild. I am also interested in wild animal welfare when working with free-ranging wildlife. In addition, we are investigating the extent of lead toxicosis in many (apparently) healthy Trumpeter Swans, as well as investigating other morbidities in individual wild animals admitted to rehabilitation centres.

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Jeremy Simpson

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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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Lindsay Robinson

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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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Graham Holloway

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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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Siavash Vahidi

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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

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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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Melanie Wills

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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 bacteria 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

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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

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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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Dave Dyck

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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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Jen Monk

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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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Ray Lu

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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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Marc Coppolino

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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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Nina Jones

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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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Michael Emes

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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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Mark Baker

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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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Jasmin Lalonde

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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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John Srbely

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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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