Multiple sclerosis (MS) is thought to be a chronic autoimmune disease of the central nervous system, which attacks myelin, a protective material that insulates nerve fibers in the brain and spinal cord. Over time, MS can cause loss of balance, impaired speech, extreme fatigue and problems with vision. Currently there is no cure, but treatment with beta-interferons (IFNBs) is available to reduce the frequency of MS attacks. After a MS patient treated with IFNBs and other medications developed liver failure, Dr. Helen Tremlett initiated research examining liver function in patients treated with beta-interferons. The research revealed that 20 to 40 per cent of MS patients treated with IFNBs developed liver enzyme abnormality.
Now Dr. Tremlett is extending her research to also investigate MS patients treated with other drugs. Since many MS patients take multiple medications, her goal is to determine whether use of other drugs increases the risk of liver injury associated with IFNBs. She is also interested in determining if MS patients taking medications other than IFNBs developed liver damage. The research could provide insights about whether people with MS are at greater risk of liver injury, and whether IFNBs are the likely cause.
Steroid hormones have profound effects on human physiology and behaviour. They are critical for the nervous system to develop and function normally, and play a role in psychiatric and neurological diseases. The levels of one steroid hormone, DHEA (dehydroepiandrosterone), drop dramatically as people age. DHEA supplements have been promoted in the media as a “fountain of youth” that can reverse brain aging and cognitive decline. However relatively little is known about the actions of DHEA on the nervous sytem and how DHEA acts at the cellular and molecular level. In earlier research, Dr. Soma showed that DHEA increases aggressive behaviour and the size of specific brain regions. Now Dr. Soma is further clarifying the effects of DHEA on behaviour and neuroplasticity (the brain’s natural ability to form new nerve cells and new connections after a change in the environment). He is assessing whether DHEA must be converted to sex steroids such as testosterone and estrogen to affect the brain. The research could improve understanding of the physiological functions of DHEA in humans, and help determine how DHEA treatment could be used to alleviate mental illness and increase neuroplasticity.
Alzheimer’s disease is the most common neurodegenerative disorder leading to dementia. The disease affects about 10 percent of people over the age of 65, and prevalence increases with age. Approximately $5.5 billion is spent in Canada each year on people with Alzheimer’s and related dementias. Deposits of the amyloid ß(Aß) protein in the brain are a characteristic feature of Alzheimer’s. Four genes, including APP, have also been linked to the disease. Processing of APP by the BACE enzyme is essential to generate the A-beta protein. In previous research Dr. Weihong Song made important discoveries about the role of presenilin proteins in the development of Alzheimer’s Disease. Now Dr. Song, who holds the distinction of being the youngest physician to graduate in China, is researching the role of BACE in the development of Alzheimer’s Disease. The research could contribute to development of BACE inhibitors, which could improve treatment of Alzheimer’s.
Access to primary care is problematic for large numbers of Aboriginal people in BC and other parts of Canada. Because of these difficulties, many Aboriginal people rely on hospital emergency departments for health care. Since emergency departments are not designed to provide comprehensive primary care, there are concerns about health outcomes and continuity of care for patients who rely on them. To plan effective, responsive services, more must be known about the ongoing use of the emergency department for health concerns that could potentially be addressed elsewhere. Dr. Annette Browne and a team of Aboriginal and non-Aboriginal researchers are exploring the factors and social contexts that influence access to primary care from the perspective of Aboriginal patients who seek care at the emergency department. Learning from the perspectives of Aboriginal peoples will be critical to the design of accessible, culturally safe, primary care services. Dr. Browne is also examining how interactions between Aboriginal patients and health professionals affect decisions about where to seek care. Findings from this research will be discussed with leaders in Aboriginal health, policy makers and health care planners to improve access to effective health care services involving Aboriginal peoples.
Nearly half of the human brain is involved in processing vision and eye movements. These functions can be impaired by strokes or brain tumours, as well as neurological disorders such as schizophrenia and autism. Using imaging technologies, experimental vision tests and eye movement recordings, Dr. Jason Barton is studying how neurological diseases disrupt the brain_s sensory and motor processing systems. Recognizing faces is one of the most demanding tasks for our visual systems, requiring both high-level perception and memory. Faces differ in only subtle ways in structure and shape, and the average person sees hundreds of faces in a day: despite this, humans are able to recognize faces effortlessly. Dr. Barton is studying how face perception is organized in the normal human brain, and how it is disrupted in patients with brain damage from strokes and surgery, and in those with Asperger_s disorder, an autism-like condition. Dr. Barton is also investigating saccades, rapid eye movements that shift our gaze toward a target and antisaccades, an unusual eye movement in which subjects look away from a suddenly appearing target. Performance on novel tasks like antisaccades can tell us something about how we exercise control over our responses to the environment. Abnormalities on such tasks can inform us about the problems with response control in conditions like schizophrenia. These studies will improve our understanding of these neurological disorders, how they disrupt visual processing, and lead to the development of future remedies.
In order to combat neurological disease and mental illness, a greater understanding of how the brain functions at the molecular and cellular level is needed. If we can learn how nerve cells form connections during development, we can develop therapies for regenerating connections following injury. Dr. Ann Marie Craig is leading an effort to understand how nerve cells form and modify synaptic connections. Her group uses a combination of fluorescence imaging, molecular biology, and electrophysiology to investigate how nerve cells communicate. By studying nerve cells growing in a dish, the scientists have already begun to identify molecular signals on the surface of nerve cells that induce contacting partners to form a synaptic connection. Mutations in one of these molecular cues has recently been linked to autism. Dr. Craig and her team are also studying how neurotransmitter receptors are localized and modified to control the strength of synaptic signaling between nerve cells. Given that synapses are the basic units of communication in the brain, the knowledge gained from understanding synapse development and modification has broad implications for the treatment of all neurological diseases and mental illnesses.
Campylobacter jejuni (C. jejuni) is the leading cause of bacterial food poisoning worldwide, infecting approximately 300,000 Canadians, three million Americans, and even higher numbers in developing countries each year. Most cases result from eating contaminated poultry; other causes include exposure to young animals and drinking contaminated water or milk. The bacteria cause severe bloody diarrhea, vomiting and fever, and can lead to more serious medical problems such as bowel disease, arthritis and paralysis. Compared to well-studied bacteria like E. coli and Salmonella, relatively little is known about how C. jejuni causes disease. Using new genetic tools, Dr. Erin Gaynor is identifying and characterizing C. jejuni genes involved in causing infection. She is examining the interaction between the pathogen and host cells to determine how the bacteria cause disease at the molecular level. Dr. Gaynor is also investigating why C. jejuni causes disease in humans when it harmlessly inhabits the intestinal tracts of many other animals, and how host systems respond to infection with the bacteria. This research may lead to a greater understanding of the mechanisms of pathogenesis for C. jejuni and contribute to the development of new treatments and potentially a vaccine to prevent infection from occurring.
The causes of many brain diseases, such as epilepsy and schizophrenia, are unknown. Researchers such as Dr. Kurt Haas are exploring the possibilities that abnormal brain development in the prenatal stage may play a role. Using a powerful gene delivery technique, Dr. Haas is investigating how nerve cell activity contributes to brain development, specifically, the effect of altered levels (i.e. too much or too little) of activity on the structure and function of neuronal circuits. This research could lead to more specific and effective interventions to prevent abnormal circuits from forming during prenatal development, and also to treat adults with schizophrenia or epilepsy.
Coxsackievirus infections can cause a variety of illnesses, including heart disease. In North America, the coxsackievirus is estimated to cause up to 30 percent of new cases of dilated cardiomyopathy, a condition in which the heart becomes enlarged and pumps less strongly. Dr. Marc Horwitz is studying how viruses such as coxsackievirus can induce autoimmune diseases such as chronic heart disease, and how immune system components shape and control development of the disease. Studies have shown that the body’s immune response has a profound effect on the development of chronic heart disease after infection with the virus, revealing that immune cells and antibodies that attack infection also damage heart tissues. Dr. Horwitz is examining how innate and adaptive immune responses following viral infection contribute to development of chronic heart disease. He will use findings from the study to design and test new methods to prevent heart disease, which could also lead to new treatments.
Tumour suppressor genes, such as ING1, help regulate normal cell growth by encoding proteins that inhibit abnormal proliferation of cells. Dr. LeAnn Howe is studying the molecular properties and function of ING1 proteins to understand the processes that lead to the development and growth of tumours. Research has linked ING1 proteins to modification of histones, the main protein component of chromatin, which makes up our chromosomes and genes. Evidence suggests that defects in regulation of chromatin structure may improperly activate or silence genes, leading to disease. Dr. Howe is examining the way ING proteins interact with chromatin to determine whether the proteins can modify chromatin. This research could help explain the role of ING1 genes in cancer development and contribute to new cancer therapies.
