Asthma is a chronic disease that affects approximately one in 20 Canadians. Research has shown an association between lower socioeconomic status and poorer outcomes for asthma patients, including more hospital admissions and emergency room visits and a greater likelihood of a fatal attack. Excessive use of short-acting bronchodilators, which help manage acute episodes of asthma, indicates inadequate asthma control and has been associated with poorer outcomes. Larry Lynd is investigating whether there is a relationship between lower socioeconomic status-measured by education, income, occupation and characteristics of residence-poor asthma control, and the overuse of bronchodilators. Confirming that relationship could determine whether inappropriate management of asthma is at least partially responsible for poorer outcomes. Larry hopes this research can lead to policies and strategies aimed at improving the management of asthmatics of lower socioeconomic status.
Program: Trainee
An evaluation of the full circle project: The effects of a theatre-based HIV prevention intervention on audience and actor/educator learning
What are the best ways to ensure young people listen to and act upon information about avoiding high risk sexual behaviours? This is the research focus for Josephine MacIntosh, who is delving into the individual, social and cultural factors that may perpetuate the epidemics of HIV and sexually transmitted diseases, especially among young women. Josephine is studying the effectiveness of using a theatre-based intervention program among youth aged 13 to 15. The theatre productions will consist of a series of original dramatic productions researched, scripted, produced and presented by youth volunteers. She hopes to develop an educational approach that can engage the audience and actors as they learn about issues such as abstinence, treatment of HIV and sexually transmitted disease, pregnancy prevention, decision-making, peer-pressure, negotiation for safer sex and alternative safer sexual behaviours.
Transcriptional regulation of HIV LTR and mechanism of HIV latency and reactivation
Anti-retroviral therapy for HIV typically suppresses the virus in patients’ blood to undetectable levels, enabling people with the infection to live symptom-free. However, some T cells are latently infected by HIV and remain unaffected even by prolonged treatment. These latently infected cells and other lymphocytes pose the major barrier to eliminating HIV infection, and provide a latent reservoir for the virus to reactivate. Long-term anti-retroviral treatment can also cause HIV resistance to therapy in some patients. An alternate strategy is therefore needed to target the latently infected virus and ultimately cure AIDS. Dr. Jiguo Chen is researching how HIV-1 establishes latency and how it reactivates. He and other colleagues in the Sadowski lab have isolated and identified a complex of several transcription factors termed RBF-2 (Ras-responsive element binding factor), which binds to HIV long terminal repeat (HIV-1 LTR) and represses HIV-1 transcription during latency. He believes that this complex plays a role in establishing and maintaining latency. He is using several different experimental strategies to determine the role of RBF-2 and to learn how it works during latency and reactivation, so new drug therapies can be designed to clear HIV from patients’ immune systems.
Susceptibility genes and environmental risk factors in Alzheimer's Disease
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.
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.