Migraines affect about 15 per cent of the population, with the incidence being two times greater in women than in men. Symptoms of common migraines include pain, nausea, vomiting, sensitivity to light, sound, and smells, sleep disruption, and depression. Progress in developing new treatments has been slow due to a lack in understanding regarding the complex genetic roots of the disorder. Familial Hemiplegic Migraine (FHM) is a sub-type of common migraines with similar symptoms, but with simple genetic roots, making FHM a good model for study purposes. Most patients with FHM experience a visual aura – such as shimmering lights, wavy images or temporary vision loss – before the headache starts and varying degrees of paralysis in one side of the body (called hemiparesis). The symptoms can last from a few minutes to several days, in some cases outlasting the headache. About 50 per cent of patients with FHM have mutations in the CACNA1A gene. Paul Adams is investigating these mutations to better understand the molecular mechanisms that underlie migraines – an important step towards developing effective new treatments to alleviate all migraines.
Program: Trainee
Entry of Dendritic Cells into the Brain: Regulation by Endothelial Cell Adhesion Molecules and Chemokines
Immune reactions in the central nervous system (CNS) – the brain and spinal cord – differ from other organs. Under normal conditions, the endothelial cells lining blood vessels in the brain act as a “blood-brain barrier” to block the entry of most immune cells into the CNS. In some CNS diseases like multiple sclerosis, and in trauma, stroke and infections, this barrier is compromised. As a result, immune cells migrate to the brain in large numbers causing inflammation, which can lead to serious consequences. Azadeh Arjmandi is studying how immune cells gain access to the brain and spinal cord in infectious, inflammatory and autoimmune diseases. Immune cells called dendritic cells have been found in the central nervous systems of patients with these diseases and their numbers increase with more chronic conditions. Azadeh is examining dendritic cell trafficking across the blood-brain barrier in order to further characterize the molecular mechanisms of inflammation in the brain. This will provide important information about how certain CNS diseases develop and may contribute to more effective treatments.
Lung disease epidemiology: evaluation of methods suitable for analyzing change in respiratory symptoms in longitudinal studies
In the past two decades, researchers have examined how lung health is affected by changes in smoking and environmental and occupational exposures, and in the process have learned a great deal about the way lung disease develops. However, most of these studies focused on lung function tests rather than information on chest symptoms, even though detailed information on these symptoms has been collected in a questionnaire used around the world since 1978. A change in symptoms, not in lung function, is the most common reason people seek medical attention and express concerns about potentially harmful workplace exposures. Victoria Arrandale is examining data on changes in coughing, phlegm, wheezing and breathlessness to determine if unused data on these symptoms can help explain the development of chronic pulmonary disease, and contribute to disease prevention through occupational surveillance programs. The results could flag early signs that have been overlooked until now. Ultimately, the goal is to lessen the impact of occupational lung disease by controlling exposures and developing early methods of diagnosing disease onset.
Characterization of SNARE complex proteins in severe mental illness
Schizophrenia is a severe psychiatric illness affecting one percent of the general population. It typically begins in early adulthood and often has a devastating effect on an individual’s quality of life and functioning in society. The diverse and debilitating symptoms associated with schizophrenia include hallucinations, delusions, dampened emotion and poverty of speech. It has been hypothesized that faulty neuronal function may contribute to these symptoms. Communication between neurons is achieved by neurotransmission at synapses. Because soluble NSF-attachment receptor proteins (SNAREs) mediate this process, they are important in neuronal communication and normal brain function. Altered levels of SNAREs have been found in patients with schizophrenia, which may mean that abnormal levels of SNARE proteins disrupt normal transmission of synapses, contributing to the disorder. Vilte Barakauskas will compare SNARE protein levels from control subjects and from people with schizophrenia to identify differences in the brain. She will also attempt to identify the significance of SNARE properties in their role in neurotransmission. This information will increase our understanding of why brain function may be altered in people with schizophrenia. By comparing protein properties between control subjects and those with schizophrenia, Vilte is looking for molecular mechanisms that may contribute to altered neurotransmission. This may ultimately lead to new treatments for, and a better understanding of, this psychiatric disorder.
Intestinal Goblet Cells and Their Role in Host Defense Against Enteric Bacterial Pathogens
An important role of intestinal goblet cells is to secrete mucus into the gut, which is believed to act as a barrier, preventing contents in the intestine from damaging intestinal tissue. However, researchers have also hypothesized that mucus secretion by goblet cells may also serve as a defense mechanism against bacterial pathogens such as enterohemmorhagic E. coli (EHEC), a bacteria that causes diarrhea and inflammation in humans. Kirk Bergstrom is investigating if, and how, goblet cells may also secrete toxins to combat infecting microbes. With a better understanding of how these cells respond to bacterial pathogens, he hopes his research may lead to new treatment options to combat bacterial diseases of the intestine.
Life at the Margins: Understanding Social Determinants of HIV/AIDS on Women's Health Through Multidisciplinary Translational Research
Vancouver’s Downtown Eastside community has the highest rates of HIV infection and the poorest health outcomes in Canada. Female sex workers in the community are among those at highest risk of infection. The limited success of public health programs and harm reduction interventions in this population reflect the multiple barriers that compromise their access to care. This includes socioeconomic factors such as poverty and unstable housing, the stigma associated with sex work, multiple addictions, and limited autonomy and personal choice. Disease control and harm reduction measures typically focus on individual responsibility, and often do not accommodate for the influences that can increase HIV risk and diminish autonomy among women in the downtown eastside. Susan Berkhout is utilizing an alternative framework developed from contemporary feminist and bioethics literature on ”relational autonomy” in order to more accurately characterize HIV risk behavior, and to produce more effective prevention and treatment strategies aimed at reducing HIV risk among female sex workers. This model considers the socioeconomic and cultural influences, and relationships involved in sex work and injection drug use. The findings should contribute to new harm reduction strategies tailored for this population, provide ethical guidance for researchers working with members of vulnerable populations, and help health care providers enhance autonomy in female sex workers.
The Role of Dopamine in Depression
Parkinson’s disease (PD) is a progressive neurological disorder that typically begins with minor motor impairments and eventually progresses to severe immobility, as well as mood and cognitive dysfunction. About 40 per cent of patients experience major depression, marked by hopelessness, inability to experience pleasure, suicidal thoughts and delusions/hallucinations. While depression is an understandable reaction to living with a chronic and potentially debilitating illness, the rate of depression in PD patients is nearly double the rate of depression seen in comparably disabled patients with other chronic illnesses, indicating the likelihood of a neurochemical element. Common to this motor disorder and mood disorder is the neurochemical dopamine, a neurotransmitter that is involved in many brain activities, including movement and emotion. Elliott Bogusz is investigating the role of dopamine as it relates to depression in Parkinson’s disease patients. He is identifying differences between depressed and non-depressed PD patients using Positron Emission Tomography (PET), a neuroimaging technology, to visualize dopamine activity in the brain. This research could provide insight into the development of Parkinson’s disease and the neurochemical activity associated with depression. It also may contribute to the development of dopamine-related therapy in the treatment of depression and to screening depressed patients for Parkinsons.
Role of Notch-1 in Neurodegeneration and Neuroprotection
Alzheimer’s disease is a neurodegenerative disorder that causes deficits in memory, language and other cognitive functions. A family history increases the risk for Alzheimer’s by about four-fold. Early onset, familial Alzheimer’s disease (FAD) runs in families, and strikes under the age of 60. Brain cells shrink or disappear, and are replaced by irregularly shaped spots, called amyloid beta plaques (A-beta). A-beta is normally found in brain cells, but harmfully accumulates in FAD – a process that is facilitated by “presenilin” proteins. FAD has been linked to multiple genetic mutations, including defects in these proteins. These proteins also decrease the production of Notch-1, a brain receptor involved in learning and memory. Notch-1 is essential for normal development, but its role in the mature brain is unknown. Kelley Bromley is investigating the ability of Notch-1 to protect brain cells from the toxic effects of A-beta plaques, and how levels of Notch-1 change during the aging process. Her research could help explain how Alzheimer’s disease develops and potentially lead to new treatments for the condition.
Bereaved family caregivers’ adjustment to loss: developing evidence to support healthy adjustment
Providing care for someone with a life threatening illness is a difficult job that taxes family members’ emotional and physical resources. Changes in the health care system have increased the amount of care family caregivers provide at home, with the result that many are caring for a loved one seven days a week for weeks and months. About half of these family caregivers report chronic illnesses of their own, and up to a third have symptoms of depression. Painful emotions experienced by family caregivers can worsen when the ill person dies. Bereaved family caregivers suffer from exhaustion and emotional distress, and are at risk for developing health problems, including illness, insomnia, anxiety and depression. Even the most resilient people experience significant distress in the early months of bereavement. Health care providers do their best to respond to bereaved family caregivers’ needs, but little is known about what helps to foster adjustment in bereavement or when particular interventions would be most useful. Moira Cairns is asking bereaved family caregivers what they find helpful and unhelpful, with the goal of determining what types of care and support health professionals can offer to reduce physical, mental and social health risks and promote healthy adjustment among bereaved family caregivers.
Structure-function relationship in smooth muscle contraction
Hollow organs such as the intestines, bladder, uterus, blood vessels, and the airways that make up lungs are lined with smooth muscle cells. Normal functioning of these organs depends on the ability of these cells to contract and relax – processes that control the volume and shape of the organs and enable them to perform their various functions. When an individual has asthma, excessive contraction of the airway smooth muscle results in airway narrowing, compromising the individual’s ability to breathe. In asthmatics, airway smooth muscle has a tendency to generate more force and shorten more extensively than in individuals without asthma. This condition is further exacerbated by the fact that the muscle cells adapt to this shorter length, making it difficult for asthmatic airways to open after an attack has occurred. Leslie Chin is studying the role airway smooth muscle plays in the development of asthma. Generally, asthma research focuses on relaxing the smooth muscle cells which is typically accomplished by using an inhaler; however, it is also important to focus on preventing these muscle cells from adapting to shorter lengths. Leslie is investigating how this adaptation occurs in asthmatics and how this adaptation is prevented in healthy people. Understanding how both the mechanics of airway smooth muscle in asthma and the alterations are altered could lead to new treatments for the disease.