Carolyn Sparrey wants to help develop new technologies and devices that prevent and improve treatment of spinal cord injuries. She’s working toward that goal by researching the biomechanical properties of the spinal cord to determine how tissues deform under various forces. This may provide new insights about the reasons the spinal cord deforms so rapidly during trauma. Sparrey ultimately wants to develop sophisticated mathematical models that simulate the injury process and accurate spine models. These models will provide valuable new tools to help in the assessment of new therapies, such as drug treatments and rehabilitation protocols for treatment of spinal cord injuries.
Research Pillar: Biomedical
Effects of amphetamine challenge on working memory in schizophrenia: A fMRI study
Christine Tipper is committed to studying schizophrenia in a multi-disciplinary manner. That’s why Christine combined cognitive neuroscience and cognitive psychology in her Master’s research on the disorder. She specifically examined the increases in brain activity that schizophrenia patients experience in areas of the brain associated with working memory — a phenomenon that is especially pronounced during acute phases of their illness. Research shows that both the acute symptoms of schizophrenia and the increased brain activity may be affected by high levels of dopamine, an important neurotransmitter (messenger) that brain cells use to communicate with each other. As one of only a few studies that have utilized fMRI (Functional Magnetic Resonance Imaging – an advanced MRI scanner) to examine the effects of a pharmacological compound, Christine studied the impact of amphetamine – an agent with neurochemical responses that partially mimic the brain’s chemistry during acute schizophrenia – on brain functions involved in working memory. The research confirmed a relationship between amphetamine dose and working memory processing efficiency, supporting the implication that both the excessive dopaminergic activity associated with acute schizophrenia, and excessive dopaminergic blockade caused by overmedication may lead to working memory deficits. Christine hopes her findings will help physicians identify individuals at high risk for developing schizophrenia, potentially leading to earlier treatment and better long-term outcomes.
Genetic analysis of natural killer cell functions
Linnea Veinotte believes immunology (studying the immune system’s functions and disorders) and molecular genetics (studying the molecular structure and function of genes) will be an important research combination in the future. Linnea worked in both areas during her Master’s Research, studying natural killer (NK) cells, unique types of lymphocytes (white blood cells). Distributed in various tissues, the cells are thought to be the body’s first line of natural defense against cancers and viruses. NK cells can kill a wide range of cancer and virus-infected cells but not normal cells. Linnea aimed to better understand their development during varying stages. Linnea discovered, unexpectedly, that a small percentage of NK cells in the neonatal and adult stage express a gene specific to T cells: the T cell receptor gamma gene (TCR). This suggests that a population of NK cells shares extensive characteristics with T cell development, and that multiple developmental pathways of of NK cells may exist. She continues to further define NK cell differentiation in her PhD program, and hopes that the research will contribute to treatments for cancer and virus infection.
Regulation of Bcl-2 family members involved in macrophage cell survival
Shih Wei Wang is examining the role of a family of proteins implicated in atherosclerosis (hardening of the arteries), a condition that puts people at risk of heart attacks and stroke. In the early stage of atherosclerosis, plaque forms along the inner lining of arteries. This occurs at sites where altered LDL blood proteins enable blood cells known as macrophages to survive. While macrophages act as scavengers to remove foreign substances from the body, macrophages also turn into foam cells that contribute to plaque build-up. Wang’s research focuses on the Bcl-2 family of proteins, including proteins that regulate cell death and others that contribute to cell survival. In experiments incorporating techniques from biochemistry, cell biology and molecular biology, Wang is analyzing proteins that influence macrophage survival and death. The research could lead to improved therapy for people with atherosclerosis, involving selective drugs that block specific proteins or enzymes.
In vivo trafficking of mutant and wild-type glucocerebrosidase-GFP chimerae
Tessa Campbell’s research has a clear purpose: improving treatment options for Gaucher disease. People with this genetic disorder lack sufficient amounts of glucocerebrosidase, an enzyme the body needs to help recycle old membrane fat. The fat accumulates in certain body tissues such as the spleen, liver, and bone marrow, resulting in problems ranging from anemia to neurological impairment. Enzyme replacement therapy helps to alleviate symptoms for one type of Gaucher disease, but the therapy’s exorbitant cost prevents many from receiving the treatment. Tessa created specially-marked versions of the gene for this enzyme, introduced them into cells, and studied the resulting protein synthesis and trafficking. Tessa also employed cutting edge RNA interference technology to further examine regulation of glucocerebrosidase protein production. Results from the research provide insights about maximizing efficiency of enzyme production and secretion, which could reduce enzyme replacement therapy costs. Results also offer further clues to glucocerebrosidase translational control and shed light upon possible involvement of inhibitory proteins in other cellular pathways.
Role of complement in the antitumor effect of photodynamic therapy and its exploitation for therapeutic gain
Ivana Cecic is investigating a novel strategy in the fight against cancer. Her research concerns the complement system, a series of proteins that help the body protect itself from harm due to infection and injury. During the course of certain diseases, such as heart attack and stroke, complement activates against tissues and can result in life-threatening consequences. Cecic conducted research that revealed complement contributes to the effectiveness of photodynamic therapy, a new method of activating light-sensitive drugs in specific tissues as part of the treatment of a variety of cancerous and non-cancerous lesions. Now she’s examining the potential of harnessing complement’s tissue-destructive power in cancer treatment involving photodynamic therapy. Cecic hopes the research will contribute to more effective treatment of malignant tumours.
Alternative Signaling of the Glucose-dependent Insulinotropic Polypeptide (GIP) Receptor
Jan Ehses is conducting research that may contribute to improved treatment of type 2 diabetes, a form of the disease that occurs most frequently in adults and obese individuals. Ehses has a particular focus on glucose-dependent insulinotropic polypeptide (GIP), a potent hormone that accounts for at least 50 per cent of the insulin secreted from the pancreas following a meal. Studies have consistently shown that GIP’s ability to cause insulin secretion is compromised in type 2 diabetes. Using state-of-the-art technology, Ehses is investigating the hypothesis that GIP affects tissues through complex intracellular networks, and that the imbalances in metabolism associated with diabetes may affect this transfer of genetic material important for regulation of insulin production. Ultimately, the goal is to provide a map of the numerous ways GIP affects the whole body, leading to information that can be applied to treatment of type 2 diabetes.
Cardiac Myocyte Apoptotic and Anti-Apoptotic Signalling Pathways Following Coxsackievirus B3 Infection
Mitra Esfandiarei has a specific goal: making a significant contribution to treatment of myocarditis (inflammation of the heart muscle) induced by a type of enterovirus (virus that comes into the body through the gastrointestinal tract). One such virus, coxsackievirus B3 (CVB3), causes severe cardiac and pancreatic diseases by directly injuring and killing heart muscle cells. In many cases, CVB3-infected myocarditis leads to cardiomyopathy (destruction of the heart muscle), for which the only available treatment is heart transplantation. Esfandiarei is studying how heart muscle cells can survive in the face of infection by CVB3. She hopes the research will enable novel treatment for viral-induced myocarditis and other cardiac conditions.
Synthesis and Evaluation of a Novel Class of Glycosidase Inhibitors for the Treatment of Type-2 Diabetes
Ahmad Ghavami’s PhD research involved a rare South Asian plant containing compounds that could be helpful in the treatment of type 2 diabetes. The Salacia reticulata climbing plant has been used for centuries in treatment of diabetes in Sri Lanka and India. Researchers have isolated compounds from the plant and demonstrated their effectiveness in inhibiting glycosidases, the enzymes that break down starch into smaller sugars, and finally into glucose. Using the compounds to inhibit these enzymes in people with type 2 diabetes could lower blood glucose concentration, which is critical in treatment of the disease. Ahmad and his colleagues designed a method to synthetically produce the plant’s compounds, together with the next generation analogues, and they tested the inhibitory effects on a wide range of enzymes. More importantly, in vivo studies with rats have shown effective control of blood glucose levels with use of Ghavami’s compounds. Results from the study confirm the effectiveness of the method for designing and synthesizing a new class of molecules that function as glycosidase inhibitors, which can control the breakdown of carbohydrates. These findings were patented, with Ahmad listed as part inventor, and were responsible for securing venture capital and the formation of a spin-off company, Mimos Therapeutics, Inc.
The Role of Homeobox Transcription Factors in Hematopoietic Stem Cell Function
For her Master’s research, Rhonna Gurevich studied the prevention of apoptosis (programmed cell death) in cardiac cells. Now she’s examining the genes that transform normal blood cells into malignant ones in leukemia patients. Gurevich is focusing on hematopoietic stem cells, which can self-renew to produce more stem cells with non-specific function or divide to create highly specialized cells to replace others that die or are lost. Maintaining the balance between stem cell self-renewal and division is a tightly controlled process. Gurevich is investigating how certain genes regulate hematopoietic stem cells, and specifically, how they may cause leukemia by disrupting the normal balance of cell renewal and division. She hopes that increasing knowledge of these genetic alterations can enable development of drugs to treat and potentially cure leukemia patients.