Bacterial infections in the intestine cause diarrheal disease worldwide, affecting people of all ages. These bacteria also trigger inflammatory conditions of the digestive tract such as in Crohn’s disease and ulcerative colitis which can lead to chronic illness and hospitalization. Growing evidence suggests that the innate immune system is critical in regulating the body’s response to early infection, and recent research suggests that dysfunction of this innate response may contribute to Crohn’s disease. A strain of Escherichia coli (E. coli) that attaches to cells on the inner lining of the intestine is a major cause of diarrhea in children, but little is known about the mechanisms by which the immune system recognizes and responds to this type of bacterial infection. Mohammed Khan is investigating how the innate immune system detects E. coli infection and the mechanisms that regulate subsequent inflammatory events in the intestine. Using laboratory-grown human intestinal cells and mouse models, Mohammed hopes to reveal novel mechanisms of regulation of inflammation in host defense. This research may lead to new treatments for infectious and inflammatory diseases of the human intestine.
Program: Trainee
Assessing risk of myocardial infarction among fire fighters
Firefighters work in hazardous environments that may put them at risk of developing diseases such as cardiovascular disease. While job-related exposure to hazardous conditions is believed to increase firefighters’ risk of heart attack, there is little data available regarding their levels of exposure to hazardous work conditions and the risk associated with health outcomes. Canadian policy-makers are seeking new evidence to help them develop compensation programs and policies with regards to the risk of cardiovascular disease associated with work-related exposures among firefighters. Tracy Kirkham’s research is directed at identifying the types of hazardous exposures that may be related to an increased risk of heart attack among firefighters. Her study includes firefighters who had a heart attack while working at one of seven BC fire departments between 1984 and 2000. She is also monitoring and analyzing firefighters’ exposure to air pollutants and noise as well as using other indicators of exposure, such as signs of physiological stress, and numbers and types of fires fought. The results of this study may provide policy-makers with information to help inform decisions regarding compensation for work-related heart disease among firefighters. In addition, the results may be applied to other occupational groups with similar exposures to hazardous substances.
Neuroprotective mechanism of connexin43
Stroke is one of the leading causes of death in North America affecting about 16,000 Canadians each year. This disease causes a sudden loss of blood to an area of the brain typically due to blocked or ruptured blood vessels. Michael Kozoriz is studying how to reduce brain damage caused by stroke. The brain has two classes of cells – nerve cells (neurons) and glial cells. Neurons conduct electrical impulses, while glia surround, support and protect neurons. Glia are the most abundant cells in the central nervous system and are connected by a junction made of a protein called connexin43. Because these cells are physically attached they have the ability to share various molecules and nutrients. Studies have shown that stroke damage is less severe in the presence of connexin43, and damage is greater if the protein is absent. Michael is examining how connexin43 protects cells from death. He suspects the junctions remain open during a stroke, allowing neighbouring cells to share nutrients, much like neighbours helping a friend in need. His findings could explain how to protect the brain during stroke, and ultimately, lead to better treatments for this disease.
Dying for choices: decision-making in end-of-life care
Every year more than 185,000 Canadians die in acute-care settings. Previous research has shown that patient choices regarding care are extensively influenced by factors inherent in the place of death. However, no Canadian research has examined how end-of-life care (EOLC) decisions are influenced and shaped through these factors. The focus of Marian Krawczyk’s research is to examine EOLC decision-making within acute-care settings, specifically in regards to the use of life-extending technologies. Her study examines factors that are overlooked in existing research including the location of communication when discussing EOLC options, differing medical models of palliative care, doctor-patient communication, and the social capital and economic resources of patients. By providing data that examines communication in EOLC in British Columbia, this research seeks to strengthen the ability of health care providers, patients and families to effectively communicate and negotiate patient care choices before and during acute care settings. The research will also increase the ability and efficiency of policy makers in the delivery and distribution of health services. Finally, it may help improve communication and decrease consumer-driven health costs.
Aging and the Brain: Is reduced function of medial-frontal cortex responsible for motor control deficits in the elderly?
Motor control deteriorates with age. For example, people over the age of 65 commit more traffic errors than younger drivers. However, it remains unclear the extent to which this increased error rate is brought about by failures of high-level cognitive control systems within the medial-frontal region of the brain as opposed to other body/brain systems. Olave Krigolson is assessing the degree to which errors by elderly individuals performing continuous motor tasks result from an impairment of error processing systems within the medial-frontal cortex. He is observing brain activity in this region of cortex during a series of experiments that will test continuous tracking and decision-making abilities—two types of tasks that are important for driving. Olave’s research will improve our understanding of why motor errors occur more frequently among older people. Furthermore, it may help develop novel techniques for assessing the functionality of motor control systems in the elderly.
Cognitive and behavioural characterization of individuals genetically at risk for frontotemporal dementia
Frontotemporal dementia (FTD) is the second most common form of dementia affecting individuals under the age of 65. Characterized by the gradual wasting away of the brain’s frontal and anterior temporal lobes, FTD progressively affects mental function, personality and behaviour, while leaving memory largely intact. Over time, they lose the ability to organize and plan, become emotionally blunted and socially inappropriate, lose insight on the impact of their behaviour, and experience difficulty with speech and language. Currently, there is no cure for FTD and treatment methods are limited. Vulnerability to some forms of FTD has been linked to a specific gene mutation that runs in families. While the symptoms of FTD are well documented, few studies have looked at the characteristics of individuals who carry the mutation but do not yet show obvious FTD symptoms. However, research shows that even when they do not exhibit obvious symptoms of FTD, individuals who carry the gene mutation perform significantly worse on tests that measure frontal lobe functioning than family members who do not carry the mutated gene. Using measures such as cognitive testing, behavioural questionnaires and brain imaging, Amanda LaMarre is seeking to establish clinical markers of FTD in genetically at risk individuals in order to identify and distinguish the earliest symptoms. She hopes that by gaining a better understanding of the development and onset of FTD, her research will provide a base for future research aimed at preventing or slowing the progression of the disease.
The function of putative streptococcal family 41 carbohydrate binding modules in carbohydrate recognition during bacterial pathogenesis
Some carbohydrates act as a “fingerprint” or marker for each cell. These markers allow cells to recognize and talk to each other, which is critical for all aspects of cell development and cell-to-cell interaction. Importantly, carbohydrate markers allow the body to discriminate between substances that belong to the body from those that are foreign in order to determine the appropriate immune response required. Further protection against foreign material is provided by protective layers of mucus at entry points to the body such as the nose, throat and lungs. These layers are derived from carbohydrates. Many disease-causing bacteria are able to attach to, and infect cells, by binding to these carbohydrates. Alicia Lammerts van Bueren is studying how enzymes called glycoside hydrolases enable bacteria to infect human cells and hide from the body’s immune system. Her specific focus is on a glycoside hydrolase found on the surface of both Streptococcus pneumonie, which is the leading cause of pneumonia and bacterial meningitis, and Streptococcus pyogenes, which causes strep throat, necrotizing fasciitis and toxic shock. All these diseases can be fatal if left untreated. Alicia’s research into the carbohydrate binding function of these enzymes may explain how these bacteria cause disease in humans, and potentially lead to new drugs or vaccines to treat bacterial infections, which is particularly important given the rise of antibiotic resistance to streptococcal infections.
Risk Assesment for Oral Cancer Prevention in the Community
Even in countries with the best survival rates, 40-50 per cent of patients with cancer of the mouth (oral cancers) do not survive five years beyond diagnosis and treatment. Late diagnosis plays a major role in this high mortality rate because oral lesions at high risk of progressing to cancer are often difficult to differentiate from lesions that are a result of trauma or infection. Denise Laronde is examining two components central to the development of an effective oral cancer screening program. She is identifying and validating tools that can be used by dental professionals to help identify which oral lesions require follow-up. She is also designing and implementing a pilot education program for dental professionals to help train them in the use of these devices. Transferring this new technology to the community may result in earlier identification of high-risk lesions, and increasing the potential for earlier treatment and ultimately, improved long-term survival.
Characterization and Thrombogenic Contribution of Platelet Microparticles to Pathogenesis of Transient Cerebral Ischemic Attacks and Unstable Angina
Platelets are cells that augment blood coagulation to form blood clots which in some cases can restrict or halt oxygenated blood flow to the heart and the brain, causing a heart attack or stroke. Although drugs like aspirin have an anticoagulant effect that can decrease the chance and severity of a stroke or heart attack, these drugs do not entirely eliminate the risk. Platelets release mini-versions of themselves, called platelet microparticles (PMPs), into circulation, which are not affected by anti-coagulant drugs. The presence of PMPs in blood is a predictor of future blockages in the brain or heart, but their precise role is not clear. Hon Leong is investigating whether PMPs have the same clotting abilities as platelets to determine whether they cause the blood clots that lead to a stroke or heart attack. Hon is examining the structure of platelet microparticles and their ability to bind to other cells and clots. The results potentially may be used to develop more accurate blood tests to predict and detect strokes and heart attacks and, ultimately, new therapies that prevent platelets and PMPs from producing harmful clots.
Involvement of myosin V in glutamate receptor trafficking in neurons
The molecules that are essential for normal brain functions are transported throughout neurons, travelling from the site of their formation to the specific location where they are activated. Defects in the transport and exchange of these molecules may affect brain activity and lead to neurological impairments such as epilepsy and mental retardation. Marie-France Lise is studying Myosin V, a family of proteins that may be important regulators of how molecules travel across neurons and reach their destinations. By characterizing how the Myosin V family regulates transport, she hopes to create a better understanding of how these processes contribute to essential brain development, learning and memory formation.