Research Location: University of British Columbia - Point Grey

Dr. Karuna P. Karunakaran is exploring a mystery around how Chlamydia pneumoniae (an infectious bacteria) is implicated in atherosclerosis (hardening of the inside of the arteries). While a strong link has been established between C. pneumoniae and atherosclerosis, 60 to 80 per cent of the adult population is infected with the bacteria with no apparent ill effects. One explanation may be that some strains of the bacteria are more capable of causing vascular disease than others, due to genetic variation. In fact, one strain of C. pneumoniae has been shown to contain a bacteriophage, a virus that infects bacteria and integrates itself into the genetic code. Preliminary studies have indicated a strong association between vascular disease and the presence of this strain. Karuna is studying the biology of the implicated bacteriophage, and hopes to identify the strains of C. pneumoniae that may cause vascular disease. This may lead to effective design of a vaccine to combat vascular disease caused by infectious bacteria.

Potassium channels comprise a group of transmembrane proteins in cells that typically allow preferential passage of K+ from the inside of the cell to its external environment. In excitable tissues such as neurons and myocytes, these channels functionally hyperpolarize the cell, serving to retard electrical conduction and excitability. In the heart, K+ channels such as Kv1.5 are of paramount importance in cardiomyocyte repolarization and governing the duration of the action potential. Since cardiac arrhythmias arise from abnormal cardiac excitability, the control of cardiac K+ channel modulation constitutes a promising site of clinical therapeutic intervention. It has been proposed that disruption of the actin cytoskeleton leads to an increased surface activity of cloned Kv1.5 channels in human embryonic kidney (HEK) cells. To investigate this hypothesis and its physiological importance, I propose to investigate cytoskeletal disruption in cardiomyocytes as well as HEK cells, examining its effect on levels of gating current in Kv1.5 and the distributions of a-actinin-2 and Kv1.5. In addition, it has been speculated that repolarizing K+ currents underlie the basis of alterations in cardiac action potential configuration occurring during post-natal development. I further propose to examine the possible postnatal changes in Kv1.5 expression contributing to this developmental dependence.

A goal that scientists have long hoped for — the ability to design drugs based specifically on the known properties of their targets — motivated Daniel Kwan’s Masters research. In order to develop such target-specific drugs, the molecular structure of potential targets needs to be well-defined. Daniel contributed to this goal by combining techniques in electrophysiology, cell biology and molecular biology to study Kv1.5, a protein controlling the movement of potassium ions from heart muscle cells. The protein acts as a pathway for ions to pass through cell membranes. Results from the research show that zinc ions and protons can block these pathways by causing a reduction in the channels available. Daniel also examined how nickel ion affects these channels and results from this study point to a possible link between zinc and epileptic seizures. These findings could help in developing drugs to block the channels as a treatment for diseases such as irregular heartbeat and epilepsy

Andy Shih’s Masters research focuses on preventing damage to cells in the central nervous system after a traumatic injury. Following such an injury to the brain or spinal cord, free radicals (oxidants) accumulate and damage almost all molecules in a cell by stealing electrons. Toxic damage to neural tissues worsens progressively over hours or days due to an imbalance between free radicals and antioxidants that normally protect the cells. Shih is examining the effectiveness of increasing antioxidants to prevent cellular damage, with a particular focus on glutathione, a potent antioxidant. He hopes this work will lead to new treatments for brain and spinal cord injuries. Shih also sees potential benefits from the research for many other diseases, including stroke, epilepsy and neurodegenerative disease.

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.

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.

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.