Research Area: Mechanisms of disease

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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Rebecca Shapiro

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To better study the biology and virulence of fungal pathogens, we are developing new genomic technology platforms for diverse fungal species. We are exploiting CRISPR-Cas9 based technologies to revolutionize the way we do high-throughput functional genomic analysis in fungal pathogens. This is enabling us to map large-scale genetic interaction networks, and uncover genetic factors and pathways that mediate important phenotypes associated with pathogenesis, antifungal drug resistance, and other biological processes associated with fungal infectious diseases.

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Shaun Sanders

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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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Emma Allen-Vercoe

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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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Scott Ryan

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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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David Mutch

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Dysfunctional lipid metabolism is a key feature of cardiometabolic diseases, such as obesity and type 2 diabetes. My research program has three primary areas of interest:
First, we are using cell and mouse models to determine how omega-3 fats regulate lipid metabolism. We are investigating how omega-3 fats control adipogenesis, as well as lipogenic, lipolytic, and triglyceride synthesis pathways in adipose tissue and liver.
Second, we are studying how different nutrients regulate omega-3 synthesis in the body using both mouse models and human clinical trials.
Third, we are interested to personalize nutrition to improve human cardiometabolic health. We continue to be active in this area through various national and international collaborations.

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David Ma

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Currently, there are several major areas of research focus including the study of basic fatty acid metabolism, understanding the association between plasma fatty acids and health outcomes, omega-3 fatty acids in the prevention of breast cancer, and examining determinants of health in the Guelph Family Health Study. In addition, related projects include the study of fats in brain health (concussion, Alzheimer's Disease), fatty liver disease, fatty acid metabolism, bone development and nutrigenomics.

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Glen Van Der Kraak

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My research focuses on the reproductive physiology of fish. We study which hormones affect ovarian follicle development and if there are hallmark responses (changes in hormone biosynthesis, receptor abundance, recruitment of downstream activators) that determine whether an ovarian follicle is destined to mature and ovulate. This research is fundamental to defining spawning success which is a prime measure of reproductive fitness and provides the toolbox that we use to examine the mechanisms by which endocrine disrupting compounds (pharmaceuticals; ammonia) and complex environmental effluents (municipal waste water, pulp mills; oils sands process affected water) affect ovarian physiology.

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Geoff Power

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Skeletal muscle is a remarkable tissue which regulates many metabolic processes, generates heat and is the basic motor of locomotion allowing us to meaningfully interact with our environment. When a muscle is activated at various lengths it produces a given predictable amount of force. However, when that muscle is actively lengthened or shortened those predictions go out the window. We actually know very little regarding dynamic muscle contraction. My research program focuses on muscle contractile properties and gaining a deeper understanding of how muscle works. I use altered states to tease out some of these fine muscle details such as muscle fatigue, aging, and training.

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Jim Uniacke

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Protein synthesis involves the translation of ribonucleic acid information into proteins, the building blocks of life. The initial step of protein synthesis consists of the eukaryotic translation initiation factor 4E (eIF4E) binding to the 5' cap of mRNAs. However, many cellular stresses repress cap-dependent translation to conserve energy by sequestering eIF4E. This raises a fundamental question in biology as to how proteins are synthesized during periods of cellular stress and eIF4E inhibition. Research in our laboratory will build upon the discovery that cells switch to an alternative cap-binding protein, eIF4E2, to synthesize the bulk of their proteins during periods of oxygen scarcity (hypoxia).

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Jamie Burr

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Our research centres on the application of physical activity and other acute/chronic perturbations to human physiology to understand how and why the body adapts to these stresses. We take an integrative systems approach, with our work focusing on interventions and assessments of cardiovascular, respiratory and muscular physiology. Specific focus areas include projects to understand the effects peripheral blood flow manipulation, the consequences of particularly stressful exercise, and novel training methods to optimize targetted physiological adaptations. From a health perspective, we are interested in understanding how exercise can be used to prevent and control risk factors for cardiovascular and cardiometabolic disease.

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Stephen Seah

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We are interested in microbial enzymes involved in the steroid and aromatic compounds degradation. These enzymes are important for bioremediation of organic pollutants and are potential targets for development of antibiotics against tuberculosis. In collaboration with Dr. Ting Zhou at Agriculture Agri-food Canada, we are isolating and characterizing enzymes capable of detoxifying the mycotoxins, deoxynivalenol and patulin. These mycotoxins contaminate grains and fruit juices.

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Elizabeth Boulding

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The current rates of environmental change experienced by animal populations are higher than have been experienced over much of fossil record. My laboratory investigates the factors that determine whether a population will adapt to a change in the environment without going extinct. Our current projects are:
1) Invasion biology, comparing scales of local genetic adaptation to exotic predators by prey with high and low dispersal potential.
2) Genomic selection and genome wide association analysis of growth, shape, pathogen resistant and life history traits in Atlantic salmon populations.
3) Assessing heritable variation in biological control of the salmon louse by two species of cleaner fish and co-operative behaviour by their client, Atlantic salmon.

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Georgia Mason

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Our research typically involves assessing animals' preferences for and responses to 'enriched' housing conditions that are more complex and naturalistic than the standard norms; investigating abnormal behaviours like stereotypic pacing; validating potential welfare indicators (e.g. facial expressions), and we also analyse multi-species datasets to looks for species-level welfare risk and protective factors. We have worked or are working with mink, rats, mice, rhesus monkeys and zebra fish; and with large datasets from elephants, Carnivora, parrots and lemurs.

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Cezar Khursigara

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Dr. Cezar Khursigara's research focuses on understanding how bacterial pathogens respond to their environment to cause disease. They are particularly interested in factors involved in biofilm formation and chronic infection. His research group is taking a multidisciplinary approach to answer fundamental questions related to how bacteria form biofilms to cause persistent infections. By combining advanced systems biology and imaging techniques, his goal is to identify potential therapeutics that can target a broad spectrum of disease-causing bacteria.

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Todd Gillis

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Ongoing projects include:
1) Examining cardiac remodeling in zebrafish and trout in response to thermal acclimation.
2) Characterizing the role of the troponin complex in regulating the function of striated muscle.
3) Examining the function of the hagfish heart during prolonged anoxia exposure.
4) Examining the change in diaphragm function during the onset of heart failure.
5) Characterizing how bitumen exposure of sockeye salmon early life stages influences cardiac development and aerobic fitness.

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Philip Millar

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The primary aim of my research is to better understand the mechanisms that control, and functional consequences of, sympathetic outflow at rest and during stress in humans with and without cardiovascular disease. To uncover these mechanisms, my laboratory employs direct intra-neural recordings of postganglionic sympathetic traffic, studying both multi- and single-fibre preparations. Additionally, we are also interested in understanding the mechanisms responsible for the large inter-individual variability in blood pressure responses to stress, as well as testing novel interventions to reduce resting blood pressure, a major modifiable risk factor for cardiovascular disease.

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Stephen Brown

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Our research is dedicated to understanding mechanisms that dictate healthy function of the human spine, and ultimately the causes and consequences of low back injury and pain. To do this we study the mechanics and physiology of the lumbar spine and its musculature. We use both human and animal models to understand different aspects of how spine movement is achieved and what "normal" movement looks like, the role of muscle in producing this movement and stabilizing the spine, and how the spine and muscle both adapt to injury and how they can be rehabilitated from injury.

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John F. Dawson

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Prof. Dawson studies the impact of inherited changes in heart muscle proteins to understand what is going wrong in patients with heart diseases so that we can develop specific strategies to treat the problem. His research takes the research from molecules to organisms, studying the biochemistry of proteins and the development and physiology of zebrafish with changes in their hearts reflecting those seen in people with diseases.
Prof. Dawson's education research focuses on learning outcome assessment in general and the development, implementation, and assessment of critical thinking through higher education science curricula in particular.

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Wei Zhang

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First, we have systematically generated inhibitors and activators for E3 ubiquitin ligases to discover new enzyme catalytic mechanism and new substrates. We continue to develop synthetic peptides and proteins to delineate biochemical mechanisms of E3 ubiquitin ligases.
Second, we showed that structure-based protein engineering enables development of anti-viral reagents for Middle East respiratory syndrome (MERS) coronavirus. Now we started engineering post-translational modifications to probe and rewire DNA damage signaling for cancer therapeutics.
Finally, we created molecular tools to increase CRISPR-Cas9 genome-editing efficiency. Now we are developing new tools as "off-switch" for CRISPR-based gene editing through targeted protein degradation.

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Jennifer Geddes-McAlister

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We are interested in characterizing the mechanisms of pathogenesis, adaptation, and survival in fungal and bacterial microbes from a systems biology perspective through mass spectrometry-based quantitative proteomics. Specifically, research in the lab centres around the following areas:
1) Systems biology to elucidate microbial proteome dynamics and interactions;
2) Mechanistic characterization of pathogenic proteins; and
3) Mass spectrometry-based proteomics for drug discovery and repurposing.

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