Dr. Robin Hsiung is researching the genetic and environmental origins of Alzheimer’s disease. The disease is the most common type of dementia, affecting five per cent of seniors aged 65 and older, and 40 per cent of people over 80. People suffering from Alzheimer’s often need costly treatments and placement in care facilities. Recent advances in molecular genetics have led to the discovery of at least four genes involved in the development of Alzheimer’s disease. However, a number of genes that are believed to be connected to the disease have yet to be confirmed. Robin will examine samples and data from two large Canadian studies of people with Alzheimer’s and other cognitive impairments. His research will identify the genes and environmental risk factors that indicate susceptibility for Alzheimer’s disease. Understanding how these risks can be modified will enable the development of new educational programs and therapies that may decrease the incidence and financial burden of this disease.
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Identification of critical gene regulatory domains using bioinformatics and comparative genomics
Over the last ten years, researchers have identified all the genes in our species—approximately 40,000 genes—called the human genome. The mouse genome will be completed soon. It’s estimated that mice and humans shared a common ancestor 70-100 million years ago, and we still share many of the same genes. Dr. Mia Klannemark is using specialized computer programs to compare data on mouse and human genes. She hopes to gain insight into regulatory regions adjacent to genes, which control the production of proteins. Mia is examining how genes make proteins, and identifying which regulatory regions have remained the same between mice and humans, because these genes indicate important functions that have not changed over the period of evolution. She is also identifying genes that have changed, which may contribute to the differences between species. This knowledge will help us understand how genetic variation influences the development of disease, and could lead to more effective treatments.
Role of Notch4 in angiogenesis
New blood vessels can grow from existing blood vessels in a process called angiogenesis. Limiting new blood vessel growth is a promising approach to treating cancer because tumours require a blood vessel supply to grow larger than two to three millimetres or to metastasize (spread) to other sites. But much remains to be learned about the molecular mechanisms of angiogenesis in tumours. In earlier research, Dr. Michela Noseda and colleagues have shown that a protein called Notch4 can inhibit angiogenesis. Notch arrests growth in the endothelial cells that line the inside of blood vessels, but it’s not known how this process occurs. In her current research project, Michela will investigate how the Notch protein prevents endothelial cells from proliferating. Ultimately, she wants to discover whether manipulating Notch activity in tumour blood vessels can induce tumour regression and limit metastasis.
Role of lipid rafts in AMPA receptor trafficking and synaptic plasticity
Brain cells communicate with one another by releasing chemical transmitters, which bind to receptors on the surface of neighbouring cells and cause them to become excited (switched on). One of the most important transmitters is glutamate, which plays a key role in learning and memory. However, the presence of too much glutamate in the brain (such as during a stroke) can lead to brain cell death. Dr. Changiz Taghibiglou is studying how lipid structures on the surface of brain cells – known as rafts – affect how glutamate is transmitted between cells. Floating on the cell membrane, lipid rafts contain channels and receptors that transmit brain cell signals. By conducting experiments that alter the composition of lipid rafts, Changiz hopes to better understand the role of lipid rafts in glutamate transmission and suggest possible ways to modulate the function of glutamate receptors and prevent cell death.
Molecular characterization of the virulence protein secretion machinery of Enteropathogenic E. coli
Enteropathogenic and Enterohemorrhagic Escherichia coli are disease-causing bacteria that cause severe diarrhoeal illness and death in young children and susceptible individuals. Often associated with hamburger disease, these bacteria are extremely dangerous when consumed, secreting proteins that cause cell disruption and damage to the human digestive tract. The resurgence of these bacteria in regional and rural water supplies also poses a considerable threat to the health of populations. Dr. Nikhil Thomas is working to improve the understanding of the mechanisms these bacteria use to cause disease. He aims to identify bacterial proteins that interact with each other to cause infection in the digestive tract. By understanding the mechanisms and strategies these disease-causing bacteria use, antimicrobials and treatments can be tested, with the ultimate goal of a vaccine to prevent disease.
Cancer Genomics: Targeting genes activated during early stage lung cancer
While early detection is key to the successful treatment of many types of cancer, tumours still often go undetected and untreated until they are well advanced. Using information generated by the cancer genomics project at the BC Cancer Agency’s Genome Sciences Centre, Dr. Greg Vatcher’s research focuses on gene expression analysis-identifying genes that are activated in the earliest stages of cancer. He is hoping gene expression analysis can help detect tumours earlier. He is also conducting work to determine if tests can predict whether a person will develop cancer, based on pre-cancer genetic changes. Greg is bringing together information from multiple genomics projects, including data from the recently-completed Human Genome Project. For example, he’s taking genetic data being gathered on the normal aging process and relating it to his cancer study to determine if there are any common genetic components.
Modulation of ligand-gated receptors by G protein-coupled receptors
Antipsychotic drugs for the treatment of schizophrenia work by blocking brain receptors for the neurotransmitter dopamine. An unusual interaction has been observed between dopamine receptors and GABAA receptors – another important type of brain receptor that inhibits brain cell activity. While these two receptors belong to two functionally different families of receptor, researchers have found that blocking dopamine receptors also reduces the number of GABAA receptors on the brain cell membrane surface. Dr. Tak Wong is studying the mechanisms by which the two receptors interact. Ultimately, he hopes to identify possible therapeutic targets that will allow better treatments for schizophrenia.
Influences of proprioceptive illusions on human action
Research indicates that people can experience sensory illusions when visual and tactile information are spatially separated. This has important implications for telesurgery, a procedure that permits surgery to be performed at a distance, but where information from the touch of hands and visual information presented on a monitor are separate and feedback is delayed. Manipulating tools under these conditions has not been as precise as hoped for. Erin Austen’s research is studying how a misperception of limb position and movement can affect the ability to accurately grasp, reach or move objects. She is also identifying ways to minimize any negative impact of such sensory illusions. The results of this research will increase understanding of how the brain coordinates behaviour and will contribute to the design of new technology in telesurgery, prosthetic limbs, telerobotics used to perform actions from a distance, and miniaturized tools for minimally invasive surgical procedures.
Glucosamine withdrawal study in Osteoarthritis
Affecting more than nine per cent of people over 63, osteoarthritis is the most common joint disease. Prevalence rises with age, so health care costs are expected to increase as our population ages. Glucosamine is a health food supplement that is widely promoted for treating osteoarthritis pain. Claims have been made that glucosamine may repair cartilage damage and cure osteoarthritis. Glucosamine use has risen dramatically as a result, but there is limited scientific evidence supporting these claims. Dr. Jolanda Cibere is conducting a study with patients taking glucosamine for knee osteoarthritis. Patients are randomly assigned to continue taking glucosamine or to receive identical-looking placebo tablets. Jolanda will assess whether people whose pain was relieved with glucosamine experience a flare up of pain when treatment stops. This research will provide insights about the effectiveness of glucosamine as a treatment for osteoarthritis pain.
The role of huntingtin interacting proteins (HIPs) in the pathogenesis of Huntington's disease
Huntington disease (HD) is a neurodegenerative disorder that causes uncontrollable movements, impairment in memory and reasoning ability, and alterations in personality. Patients with the disease carry a mutation in the HD gene, which results in an expanded tract of glutamine (an amino acid). The gene product is therefore a mutated form of the HD protein. This expanded tract disrupts the interaction between the HD protein and other proteins that work together to perform essential cell functions. A modified interaction may alter the normal function of any of the interacting proteins, making specific cells vulnerable to premature death. Anat Yanai is studying the cell biology of several HD interacting proteins, including the way they interact with proteins involved in cellular metabolism and the alterations in their normal function as a result of the mutation in the HD gene. The findings will assist in developing therapeutic strategies for Huntington patients, such as inhibitors or activators of these interactions.