Genes regulated by the androgen receptor in prostate cancer cells

Dawn Bradley’s research focuses on the key role of the male hormone androgen in prostate cancer, the second leading cause of death for men with cancer in North America. Prostate tumours initially need androgen to grow and proliferate, but tumours can progress to the point where they survive without androgen. Conventional treatments are ineffective when prostate tumours become androgen-independent. Bradley is investigating the process by which the androgen receptor regulates various genes. Using microarrays, a technology that allows thousands of genes to be examined in a single experiment, she hopes to identify genes that are regulated by the androgen receptor and other genes that progress to androgen-independence. Her research will improve understanding of how prostate cancer cells become androgen-independent and provide potential targets for anti-cancer therapies.

Cytoskeletal modulation and developmental regulation of Kv15 surface expression

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.

Single Channel analysis of the mechanism basis of Zn 2+ and H+ medical block of Kv1.5

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

Identification of caspase modifiers via genetic selection in yeast

Elaine Law’s Masters research literally related to matters of life and death. Elaine investigated apoptosis – the process of programmed cell death. Apoptosis plays a critical role in normal body function by eliminating unwanted and potentially dangerous cells as part of tissue renewal. However, too much cell death can lead to strokes and neurodegenerative disorders such as Alzheimer’s Disease and Huntington’s disease, while too little cell death has been associated with many forms of cancer and autoimmune diseases. Using yeast as a host and advanced genetic techniques, Elaine studied caspases, a group of proteins that play a key role in cell death. She developed a genetic selection system in yeast for identifying caspase modifiers: proteins that either activate or inhibit caspases. Her research improves understanding of cell death and provides insights about genes that contribute to abnormal patterns of cell death leading to cancer.

Identification of Notch4-Modulated Genes in Vascular endothelia Cells

Graeme McLean’s research focuses on angiogenesis, the process by which a person’s existing blood vessels sprout extensions from themselves to enhance blood flow or nutrient delivery. The process is critical in embryo development, wound healing and inflammation. Defects in angiogenesis can interfere with wound healing and contribute to conditions such as rheumatoid arthritis. Abnormal patterns of angiogenesis also contribute to the growth of cancerous tumours that are capable of co-opting the process to increase their blood supply. In addition, the ability to increase blood flow to the heart is crucial to the survival of heart attack victims. McLean is studying Notch4, a protein in endothelial cells that line the blood vessel wall and participates in the regulation of angiogenesis. Investigating how this protein works will lead to a better understanding of angiogenesis and provide insights into correcting defects in the process.

Calcium Homeostasis and Basal Entry in Vascular Smooth Muscle

Much research has been devoted to understanding how calcium enters stimulated vascular smooth muscle and causes muscle contraction. Defects in this process have been linked to diseases such as hypertension and peripheral vascular disease. But little research has been done on calcium entry in unstimulated muscle. Damon’s research suggests that a significant amount of calcium enters muscle even in the absence of a contraction-inducing stimulus. By investigating the pathways through which calcium enters vascular smooth muscle and skeletal muscle, Mr. Poburko aims to identify the specific role of calcium entry in causing diseases such as muscular dystrophy and chronic hypertension. Ultimately the research may point to new drug therapy targets for the diseases.

The role of cystine transport by the xCT protein in maintaining the brain antioxidant glutathione

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.

Material properties of the spinal cord

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.

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.