Depression is a widespread mental illness, affecting one in ten people. Twice as many women as men suffer major depression. Hormonal changes brought on by puberty, menstruation, menopause, and pregnancy may contribute to the higher risk, as these periods in a woman’s reproductive cycle have been associated with depression. Hormone replacement therapy has been prescribed to treat changing sex hormone levels, but a study found the health risks exceeded the benefits. Carolin Klein is investigating the impact of an alternative approach, cognitive-behavioural therapy (CBT), on hormone levels. CBT has been as effective as medication in treating depression, with no side effects. If depression and sex hormone levels are related, cognitive-behavioural therapy could also normalize hormone levels. Carolin is measuring hormones in depressed men and women before, during, and after CBT. The results could clarify if changing hormone levels cause depression, and lead to greater use of cognitive-behavioural therapy to treat abnormal hormone levels, without the side effects associated with some medications.
Neurons (nerve cells) in the brain and central nervous system relay messages to each other by releasing neurotransmitters. For the message to be received, neurotransmitter receptors and associated proteins must be strategically transported to the synapse, the site of contact between neurons. Defects in the transportation of proteins is thought to affect neuronal activity and ultimately may lead to neurological impairments like epilepsy and mental retardation. Marie-France Lise is studying this fundamental process – how the molecules important for normal brain functions are transported throughout the neurons from their site of synthesis to their specific site of action. Her research focuses on a family of neuronal proteins known as Myosin V, thought to be important regulators of protein transport. These proteins act as molecular motors by binding and “walking” cargoes along actin filament highways, leading to different destinations within the cell. By characterizing how the Myosin V family regulates transport of proteins in neurons, Marie-France hopes to gain a better understanding of how synapses are formed during brain development, learning, and memory formation.
Successful kidney transplants significantly improve physical and psychological health and life expectancy for recipients. However, a kidney transplant’s impact on cognitive abilities (brain functions such as awareness, perception and reasoning) is relatively unknown, even though cognitive impairments have been reported in patients on dialysis treatment for chronic kidney disease. Other factors can also impact cognitive function, including other illnesses and medication regimens. Patients with chronic kidney disease are also at considerably higher risk of emotional distress than their peers. To determine if cognitive capacities improve following a transplant, Shannon Lund is conducting one of the first studies comparing cognitive differences between patients on dialysis and those who have received kidney transplants. Shannon is specifically comparing cognitive function, depression, anxiety and coping styles in groups of patients, before and after transplantation. The research could help clarify the source of cognitive deficits in patients with chronic kidney disease before and after kidney transplantation, and help health care professionals develop more effective treatment strategies to improve care of these patients.
Non-Hodgkin’s lymphoma (NHL) is the fifth most common cancer in Canada, and incidence has been increasing steadily for the past 30 years. However, at present, little is known about the risk factors for developing this cancer of the lymphatic system. Danhong Shu is examining whether exposure to organochloride compounds (chemicals such as DDT and PCB) increases the risk for developing Non-Hodgkin’s lymphoma, and whether certain genetic factors may also contribute to increased or decreased susceptibility to NHL. Using blood and mouthwash samples from 1,600 test subjects, she is comparing organochlorine levels between people with NHL and those who are cancer free. In addition, Danhong is using these samples to compare genetic patterns that may point to increased susceptibility to this type of cancer, focusing on genes involved in the metabolism of organochlorines (Ahr and CYP1A1). This research could confirm environmental risks and genetic susceptibility for Non-Hodgkin’s lymphoma, and help explain how the disease develops. Ultimately, the information may lead to preventive measures to limit environmental exposures and reduce the risk of NHL.
The Bordetellae are respiratory pathogens that can cause severe infections in both humans and animals, including whooping cough. In spite of widespread vaccination, whooping cough is undergoing resurgence worldwide, including a peak of 1,800 reported infections in British Columbia in 2000. Autotransporters are the largest class of secreted proteins produced by Bordetella and other Gram-negative bacteria. They possess a characteristic domain that facilitates their export from the cell, which is a factor implicated in microbial virulence (disease causing ability of infectious agents). Recently, a novel autotransporter (BapF) was identified from the genome sequences of Bordetella, and is predicted to be modified by lipids. Although lipid-modified autotransporters are rare, known ones contribute significantly to virulence in their respective organisms, and little is known about their mechanism of secretion. Peter Sims is investigating the role of BapF in the disease-causing properties of Bordetellae. His work will determine whether BapF is expressed (activated) in these bacteria, and how this autotransporter is secreted. Research into BapF may reveal new information regarding protein secretion in bacteria, and provide potential targets for fighting infection.
The well-being of health care workers and a healthy work environment are critical components of an effective health care system. According to the Workers’ Compensation Board of BC approximately 40% of all violence related claims come from health care workers. In a survey of St. Paul’s Hospital in Vancouver, 66% of employees had experienced physical assault in the previous year. Despite the increasing recognition of the severity and impact of violence in the workplace, there have been few studies that have investigated the impact of workplace strategies and interventions that mitigate violence in the workforce. Rakel Kling is examining the overall effectiveness of a violence-reduction intervention in the health care industry. Her research is specifically investigating the rate of violence-related incidents among health care workers at Vancouver General Hospital (VGH) over a five year period and examining the differences in rates by year and unit type. She is also examining whether there is a reduction in healthcare worker injuries as a result of the implementation of a new patient risk assessment system. Results from Rakel’s research will help guide policy and program decisions surrounding violence prevention measures at VGH and ultimately other hospitals and health care facilities in the province.
In mammalian cells, DNA is packaged into a tight structure called chromatin. The DNA in cells can be damaged by a number of agents, including ultraviolet light, and failure to repair damaged DNA can lead to genetic mutations that can kill cells or induce cancer formation. In order for core DNA-repair proteins to access damaged genetic material, the condensed chromatin structure must be relaxed. The protein ING1b (a growth inhibitor) is known to enhance the repair of DNA in ultraviolet-injured cells by relaxing the chromatin structure. Conversely, mutations in the ING1b gene within a region called the PHD finger have been shown to reduce DNA repair and have also been correlated with reduced survival of patients with melanoma (an aggressive form of skin cancer). Building on the research findings of his supervisor, Dr. Gang Li, William Kuo is studying the mechanisms through which ING1b assists DNA repair. He hypothesizes that ING1b associates with a class of chromatin-modifying protein complexes, called histone acetyl transferase (HAT) to induce chromatin relaxation. He will also explore the possibility that the PHD finger tethers the ING1b-HAT complex to chromatin for its relaxation during DNA repair. He hopes that an understanding of these mechanisms could lead to the development of new therapies for cancers caused by damage to DNA.
A growing field in the world of immunology is the study of T regulatory cells (Tregs), a specialized subset of T cells that has the ability to “”turn off”” the immune system after an infection has been cleared. While research has been focused on how Tregs suppress one class of lymphocytes (Th1 and Th2 cells) from proliferating and making molecules that are involved in activating the immune system, the effect of Tregs on the other major class of lymphocytes – the B cells – has received far less attention. Previous experimentation in the laboratory of Grace Lam’s supervisor, Dr. Anthony Chow, has revealed that one injection of Toxic Shock Syndrome Toxin (TSST-1) to cell cultures induces a massive systemic inflammatory response. However, repeated injections of this toxin leads to the activation of Tregs that “”calm down”” the immune response. Grace’s own research has shown that TSST-1 induced Tregs may be able to prevent activation of B cells by suppressing B cell proliferation and/or inducing B cell death. Now, she is studying the mechanisms by which this down regulation occurs. This work holds important promise for understanding and developing more effective treatment for chronic health problems caused by an overactive immune response. Diseases such as systemic sclerosis, systemic lupus erythematosus, or rheumatoid arthritis, all result from overactive B cells producing excessive amounts of antibodies that damage normal tissue. Grace hopes her research might open the possibility of employing TSST-1 induced Tregs to shut down this abnormal immune response.
Methanol and ethylene glycol are the principle ingredients in automotive antifreeze products. When ingested, the result is organ failure and death unless treatment is initiated within hours of exposure. Survivors are at risk for blindness from methanol, or severe kidney damage from ethylene glycol, which can require weeks of dialysis. Treatment of methanol and ethylene glycol poisoning includes antidote therapy and use of dialysis to remove the poison. There are currently two antidotes available: ethanol and fomepizole. Ethanol is inexpensive but difficult to administer and causes many adverse effects. A new antidote, fomepizole, is relatively free of adverse effects, easy to use, and may prevent the need for dialysis in some patients, but it is very expensive. Katherine Lepik, a pharmacist with the BC Drug and Poison Information Centre, is researching the incidence, severity, mortality, and cost of methanol and ethylene glycol poisoning in BC. She is examining which age groups are at greatest risk for poisoning, why people are poisoned, and how to use health databases to monitor rates and severity of methanol and ethylene glycol poisoning. Her goal is to help prevent poisonings and ensure hospital staff have the resources and training to appropriately treat patients.
The placebo effect, when a patient’s beliefs or expectations can influence the course and outcome of disease, is a well-recognized medical phenomenon that is particularly prominent in neurological disorders such as depression, pain and Parkinson’s Disease. But little research to date has examined the therapeutic impact of taking placebos and the mechanism by which they work. Studying the placebo effect is also important to assess the need to control the phenomenon in clinical trials, and to address the difficulty in detecting a true therapeutic effect when benefits are masked by a strong placebo effect. Sarah Lidstone is using advanced imaging techniques to assess the physiological changes in the brain associated with the placebo effect in Parkinson’s Disease. Sarah is studying how a patient’s expectation about their treatment influences how they respond to that treatment. Her group has already discovered that a placebo can induce the release of dopamine in the brains of Parkinson’s patients. A deficiency of dopamine, a chemical that transmits messages between brain cells involved in controlling movement, causes Parkinson’s Disease. The research could help explain how the placebo effect occurs in Parkinson’s, and improve treatment for the disease, along with drug addiction, depression and pain.