Identification of Phosphoregulation pathways involved in Hematopoetic Stem cell self-renewal

In recent years it has been suggested that hematopoietic stem cells (HSCs) possess the ability to develop into different types of tissue in the body. Conceivably this phenomenon could one day facilitate treatment of a variety of degenerative diseases via harvesting a patient’s own HSCs, genetically modifying them, and then transplanting them back into the body. Unfortunately at present there is no effective way to maintain HSCs outside of the body, as the cells self-renew only in response to the unique combination of growth factors present within the specialized environment of the bone marrow. Michael Long is comparing how different environments affect the pathways by which HSCs receive chemical signals to renew. By studying HSC activity within bone marrow as well as an environment that does not promote HSC renewal such as the spleen he hopes to determine which signalling pathways are vital for HSC renewal. Ultimately, this information may allow researchers to identify how to recreate an environment outside the body that promotes HSC growth.

The role of social support in coping with chronic low back pain: help or hindrance?

Approximately 14 per cent of Canadians suffer from chronic low back pain, making it the second most common chronic condition in the country. Some studies suggest that having a high level of satisfaction with social support may increase well-being of people with chronic back pain. However, there is little research that has addressed the potentially harmful effects of social support. Susan Holtzman is examining how support networks help or hinder patients in coping with chronic back pain over time. She will study 200 patients and their partners, using questionnaires and daily records to track pain levels, disability, mood, types of support received, satisfaction with support, coping strategies, and health. Findings from this research may lead to more effective and individualized treatment programs.

Barriers to access and willingness to participate in an intervention program to reduce the incidence of HIV and Hepatitis C among drug dependent youth

In her Masters research Cari Miller showed there is a high prevalence and incidence of HIV and Hepatitis C among young injection users in Vancouver. Those at highest risk for HIV are young females and Aboriginal youth. Her research suggested that preventing infection requires a complex response, addressing risky drug and sexual behaviours. Cari is building on her earlier research to investigate the barriers to accessing current prevention tools such as clean needles and condoms. As well, she is examining the willingness of youth to participate in a behavioural intervention to reduce the risk of HIV and Hepatitis C. The research will inform policy on current methods of prevention and possibly help to develop new ones. Cari’s work could also help empower youth to better care for their health and for the health of their peers.

Molecular mechanisms of SP12-mediated virulence in Salmonella Typhimurim

Salmonella enterica serovar Typhimurium is a bacterium that causes gastroenteritis, a type of food poisoning characterized by abdominal pain, fever, vomiting, and diarrhoea. Most Salmonella infections arise from oral ingestion of tainted food or water and are a significant cause of disease and death in animals and humans worldwide. Dr. Brian Coombes is studying the molecular mechanisms by which Salmonella use virulence factors to modify their host environment. Once injected into mammalian host cells, these virulence factors rearrange and reprogram the cells so that Salmonella can replicate and evade the body’s immune system. Learning more about how bacteria use specific virulence factors to manipulate their environment during infection may lead to the design of new therapeutic strategies to treat or block the disease process.

A postdoctoral program to enhance planning and quality improvement initiatives in mental health through the validation of administrative mental disorder diagnoses

While a number of significant improvements in treatment of mental disorders have been made in recent years, gaps remain. For example, major depression is identified in only 50 per cent of people with the disorder when they visit their family doctor, and only half of those people receive appropriate treatment. Initiatives to address these gaps include programs that provide public and physician education and increase connections between care providers. However, it’s unclear how successful these initiatives will be due to a lack of data on the prevalence of mental disorders and whether people improve as a result of these programs. Dr. Paul Waraich is evaluating whether data routinely collected from hospital and physician visits, as well as medication prescriptions, are of sufficient quality to be used to evaluate changes in the care of major depression and other mental disorders. The research could greatly improve understanding of whether new mental health care programs are effective.

Regulation of NMDA receptors and excitotoxicity

Glutamate mediates signaling between neurons (nerve cells) by binding to protein receptors. Over-activation of one type of glutamate receptor, NMDA, can result in damage to neurons. Dr. Lynn Raymond is researching how neuronal activity and cell proteins regulate NMDA receptors, with the goal of better understanding how irregularities or disruptions in regulatory pathways are implicated in damage associated with neurological disease. Dr. Raymond is especially interested in Huntington’s Disease. This inherited neurological disorder causes progressive neurological damage in specific brain regions leading to movement abnormalities, personality changes, psychiatric disorders and memory loss. Studies have suggested that over-activation of NMDA receptors plays a major role in this selective destruction of brain cells. Dr. Raymond is investigating interactions between mutant huntingtin (the protein produced by the Huntington’s Disease gene) and NMDA receptors to gain a more detailed understanding of the causes of neuronal death in Huntington’s Disease – research that may help in the development of new therapies for this incurable disease.

Centre for Complex Disorders

Serious mental disorders affect thinking, mood and behaviour. The consequences are suffering, impaired function in daily life and yearly costs estimated in Canada at tens of billions of dollars. Like diabetes, hypertension and asthma, mental disorders are complex disorders, meaning there is no single gene mutation, experience or environmental effect that can be held responsible. With a history of focused but isolated research strategies that have failed to address these complexities, present day treatments for schizophrenia and bipolar disorder are no more effective than those developed 50 years ago. There is also a lack of effective treatments for Alzheimer’s disease. The Centre for Complex Disorders (CCD) will seek integrative and transformative solutions to these health problems, with an initial focus on psychotic illnesses, such as bipolar disorder and some types of depression. These often begin in adolescence and cause those affected to lose contact with reality, and chronically become socially isolated and unable to work. The unit’s secondary focus will be complex disorders affecting memory in old age.

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The contribution of hepatic ABCA1 to HDL levels and composition, and suceptibility to atherosclerosis

Coronary artery disease is a leading cause of death among Canadians. High cholesterol has been identified as a major risk factor for the disease. However, there are two kinds of cholesterol: LDL, the so-called “bad” cholesterol that has been linked to coronary artery disease, and HDL, the so-called “good” cholesterol that has been linked to lower incidence of heart disease. Currently, the medical community’s focus is on decreasing LDL levels, but more than fifty percent of people with premature coronary artery disease have low levels of HDL. A gene called ABCA1 has been identified as critical in the production of HDL, but there is still uncertainty about its function. ABCA1 exists in most tissues of the body, but some tissues – notably the liver – are particularly rich in it. Liam Brunham is investigating the role of ABCA1 in the liver and in the production of HDL. Learning about this gene will increase understanding of how the human body produces and uses cholesterol and how it responds to different diets.

Facial indicators of heart rate reactivity in a stress induced state

Studies show that stress can increase the risk of heart disease and other conditions. Therefore, identifying people who are most likely to have strong reactions to stress is an important goal in the prevention of heart disease. David Nordstokke believes facial expressions may be key markers for identifying people at risk of stress-induced heart disease. He is studying the relationship between facial expressions and stress by giving participants a test of social anxiety. During the videotaped test, David compares changes in heart rate with specific facial movements to determine if there is a link. He hopes the research will reveal patterns of facial expression that provide information about heart rate reactivity. Ultimately, David aims to help health care practitioners in the early detection of individuals at risk of developing heart disease so they can intervene with stress management programs.

Evaluation of common drug review dissemination and use of evidence by drug plans

The cost of publicly funded prescription drug programs in Canada is growing an estimated 15 per cent a year. Studies show drug plan staff have little time to reassess drugs already on the market and are overwhelmed with submissions from pharmaceutical companies seeking approval of new drugs. In September 2001, federal, provincial and territorial Health Ministers launched the Common Drug Review (CDR) to develop a national process for reviewing evidence on new drugs and reducing duplication among provinces. How CDR will integrate with current communication systems to share information between drug plan staff and researchers is not yet clear. Mowafa Househ is assessing how drug plans use and produce evidence within the CDR system, and how virtual networking can improve the exchange of this knowledge. Using web-based conferencing, Mowafa is developing a three-step protocol to improve links between drug plan manager and researchers. He is applying the protocol to three major drug plan issues: assessing new drugs, re-assessing existing drugs, and evaluating the impact of drug policies.