The role of the stem cell antigen, CD34, on mature murine mast cells

In earlier research supported by a MSFHR Masters Trainee Award, Erin Drew disproved theories that CD34, a cell surface protein, was specific to immature blood cells. She found CD34 on immature blood cells, but also on cells lining the blood vessels and on mast cells. Mast cells are known to play a pivotal role in allergic and asthmatic responses. Erin’s work now focuses on CD34’s function in mast cells and how the protein prevents inappropriate adhesion to other cells and tissues. These enquiries will increase new knowledge on how blood cells move around the body and how mast cells can invade tissues and respond to allergens. Ultimately, Erin hopes her work will lead to the identification of targets for the treatment of allergies and asthma.

Bi-specific antisense and RNAi targeting of IGFBP-2 and IGFBP-5 as a novel treatment strategy for delaying progression and bony metastasis of prostate cancer

Prostate Cancer is the most common cause of cancer and the second leading cause of cancer death in men in North America. But removing the androgens (male sex hormones) that regulate tumour growth — the only existing therapy shown to prolong survival — only produces temporary remission. Surviving tumour cells usually recur, becoming androgen independent. To improve survival, new therapeutic strategies must be developed. Dr. Alan So is exploring a novel way to treat prostate cancer at the molecular level. He is observing how prostate cancer is affected by shutting down two common genes in prostate cancer cells: IGFBP-2 and IGFBP-5 (insulin-like growth factor binding proteins). These genes are essential for prostate cancer to grow and spread to the bones. His research is also examining the effect of combining this treatment with chemotherapy on prostate cancer cells. The ultimate goal is to develop a more effective treatment for prostate cancer that can be tested in clinical trials.

A finite element model of the spinal cord

The way spinal cord tissue responds to different forces is not well understood. Carolyn Greaves is designing a specialized computer model of the spinal cord and its surrounding structures to measure the impact of different types of injury. This type of model of the spinal cord, called a finite element model, has never been developed before. The model will provide detailed measurements of spinal cord response to internal stresses, strains, and pressure changes in spinal fluid, as well as the impact on blood vessels, grey matter (nerve cell bodies) and white matter (nerve fibres). This information will broaden understanding of spinal cord injuries and be used to evaluate potential treatments. As well, neurological changes-such as swelling-occur following a spinal cord injury and can lead to secondary injuries. Carolyn’s model may lead the development of other models that could provide better understanding of these secondary injuries and how to treat them.

The role of the integrin-linked kinase in intestinal inflammation

Affecting roughly one in 1,000 people in western populations, inflammatory bowel disease (IBD) includes both Crohn’s disease and ulcerative colitis. These conditions cause chronic inflammation of the large and small bowel and ultimately lead to severe tissue damage. Current therapies can relieve and treat symptoms, but neither a cause nor a cure has been established for these disorders. It is believed that integrin-linked kinase, an enzyme that is known to be responsible for a number of different cellular functions, may play a key role in IBD. Kuljit Parhar is investigating the role of integrin-linked kinase in regulating the chronically activated inflammatory response found in IBD. Learning about how the inflammatory response is regulated could lead to more effective treatments for IBD.

Identification and characterization of proteins that interact with the androgen receptor to modulate its activity

Prostate cancer is the second leading cause of cancer-related deaths in men. Advanced prostate cancer is often treated with androgen withdrawal therapy, which blocks the growth-promoting effects of androgens (such as testosterone). Unfortunately, while this treatment is initially effective in reducing prostate growth, the usual outcome is an untreatable, androgen-independent form of cancer, where the prostate gland grows without androgens. Latif Wafa is investigating how this change to androgen-independent growth occurs. He is focusing on the process in which androgen binds to a receptor that is essential to prostate growth and death. The receptor is believed to continue to have a role in prostate growth even when androgens are blocked. Latif is looking for possible genetic alterations to the receptors, as well as potential changes to other proteins that also interact with the receptors. Ultimately, he hopes to identify new molecular targets to block prostate growth in advanced cancer.

Role of PI3-kinase family in phagocytosis and phagosome maturation

Successful host defense against microorganisms relies heavily upon a population of immune cells called macrophages. These cells are capable of ingesting and destroying pathogens such as bacteria and yeasts. Jimmy Lee’s research will investigate the cellular mechanisms involved when macrophages ingest and destroy pathogens. Specifically, he is studying a protein family called PI(3)K, which is responsible for activating many cellular activities and is believed to enable macrophages to ingest microorganisms. He aims to identify the specific PI(3)K protein involved in this process. This research will increase the understanding of how the body responds to infection and may lead to the design of specific therapeutic approaches to fight infections.

AMPR receptor trafficking and membrane surface expression in models of cerebral ischemia (stroke)

A common consequence of stroke or heart attack is brain cell death. Studies indicate that an increase in AMPA, a type of neurotransmitter receptor on the surface of brain cells, may be one of the critical causes leading to brain cell death during a stroke. Yitao Liu is investigating the mechanisms that lead to an increase of AMPA receptors on the surface of brain cells. He hopes his work contributes to a better understanding of how brain cells die following a stroke and suggest ways to limit the activity of AMPA receptors and decrease brain cell death.

Effectiveness of CBT for panic disorder: Treatment outcome in research and community settings

About 37,000 people in BC suffer from panic disorder, a debilitating condition characterized by recurrent panic attacks, intense fear and anxiety. Common symptoms include heart palpitations, sweating, nausea, dizziness, numbness in the extremities, and hot or cold flashes. Panic disorder is also costly to our health care system: two-thirds of patients in Canada have sought psychiatric care, 21 per cent visited emergency departments (sometimes repeatedly), nine per cent saw a cardiologist, and 17 per cent saw a neurologist in an effort to understand their symptoms. Recent lab studies have shown cognitive behaviour therapy significantly decreased the frequency and severity of symptoms and achieved better outcomes than other treatments and medications for panic disorder. In her doctoral research, Kathleen Corcoran is comparing these results to outcomes among patients in two community settings-a community mental health clinic and the Anxiety Disorders Unit at UBC Hospital-to determine whether cognitive behaviour therapy is as effective in treating panic disorder in a less controlled, real-life setting.

The effects of bone mineral density (BMD) testing on behaviour change over 3 years

Osteoporosis develops when bone density deteriorates, which causes bones to become fragile and fracture easily. Little data exists to demonstrate whether people modify their lifestyle after receiving bone density test results that indicate they are at risk of osteoporosis. Elaine Kingwell is assessing whether bone density testing influences people to seek information about osteoporosis and to adopt preventative behaviours believed to have a positive impact on bone density. The behaviours include increasing calcium and vitamin D intake, participating in physical exercise, and taking medications to prevent and treat osteoporosis. Elaine is also studying the way bone density test results are communicated to patients, to determine whether people are more likely to make lifestyle changes when they receive their results directly or when results are sent via their family physician.

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.