cihr_grants
53,420 rows
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| external_id ▼ | title | project_lead_name | co_researchers | institution | province | country | competition_year | award_amount | program | program_type | theme | research_subject | keywords | abstract | duration | source_url |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 163301 | Granzyme B in Hair Follicle Growth | Granville David J | Granville, David J; McElwee, Kevin J | University of British Columbia | British Columbia | Canada | 200802 | 99927.0 | Catalyst Grant: Skin Diseases and Conditions | Operating Grants | Biomedical | Musculoskeletal Health and Arthritis | Alopecia; Alopecia Areata; Apoptosis; Atherogenesis; Granzyme B; Growth Regulation; Hair Follicles; Hair Growth Cycle | Hair loss is a common and distressing problem which can affect men, women, and children. There are several different types of baldness including androgenetic alopecia, better known as pattern baldness, and alopecia areata, a condition that involves immune cells targeting hair follicles and causing patchy hair loss. Recent research on patients has suggested that there may be a link between having androgenetic alopecia and susceptibility to having a heart attack. The research groups of Dr Granville, an expert on heart disease, and Dr McElwee, an expert on hair loss, have teamed up to look for the biological factors that could link baldness to increased risk of heart disease. Our preliminary investigation has suggested that some rodent models susceptible to heart disease are more likely to develop hair loss while models resistant to heart disease have increased hair growth. Equally, a rodent model of alopecia areata is more likely to have heart problems. Biological factors that cause cell death in heart disease, particularly one called granzyme B, also seem to be expressed in hair follicles. We saw levels of granzyme B increased with the development of alopecia areata. These initial observations suggest granzyme B might be a biological link between heart disease and hair loss. Our proposal involves looking at granzyme B in the skin and how it may alter hair growth. We intend to; 1)determine the expression of granzyme B in hair follicles and how expression changes as hair follicles grow, 2)examine the effects of granzyme B deficiency on normal hair follicle growth, and 3) examine the effects of suppressing granzyme B expression in an alopecia areata disease model. We anticipate that increased granzyme B activity is associated with increased hair loss and suppressing it may inhibit hair loss. It is possible that an increased granzyme B action evident in alopecia may reflect an increased granzyme B mediated activity in heart disease development in the same individual. | 1 yr 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=163301&lang=en |
| 163302 | The role of Periostin in promoting epithelial-myofibroblast transition and avoidance of apoptosis in cutaneous wound healing | O'Gorman David B | O'Gorman, David B; Dagnino, Lina | Western University (Ontario) | Ontario | Canada | 200802 | 53013.0 | Catalyst Grant: Skin Diseases and Conditions | Operating Grants | Biomedical | Musculoskeletal Health and Arthritis | Epithelial-Mesenchymal Transition; Mouse Model; Myofibroblast; Periostin; Scarring And Fibrosis; Wound Healing | Wound healing abnormalities has been estimated to affect at least 4.5 million people in North America. Normal wound healing is an orderly and efficient process that includes the conversion of cells, commonly referred to as fibroblasts, into myofibroblasts to contract the edges of the wound together. Normally myofibroblasts undergo cell death after the wound is contracted, however in abnormal healing situations such as scarring, myofibroblasts are evident in increased numbers and persist after the wound has healed. In addition to the fibroblasts resident in the dermis, it has recently been suggested that these cells may arise through the conversion of cells in the epidermis into myofibroblasts in the dermis, a process known as epithelial-mesenchymal transition (EMT). EMT occurs in fetal development and cancer cell formation. Recently, the protein Periostin has come under intense scrutiny in cancer research, where it has been shown to promote EMT and enhance tumor cell persistence. We have previously shown that Periostin is transiently expressed during normal skin wound healing and that it persists in scar tissue. This research proposal will address whether Periostin induces EMT and promotes myofibroblast formation from epidermal cells during normal wound healing. We will also investigate whether Periostin can enhance myofibroblast survival in scar tissue. These studies have the potential to identify Periostin a target for therapies to reduce scar formation and other abnormal wound healing conditions. | 1 yr 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=163302&lang=en |
| 163305 | Understanding the molecular determinants of shingles | Pearson Angela | Pearson, Angela | INRS - (Québec, QC) | Québec | Canada | 200802 | 76121.0 | Catalyst Grant: Skin Diseases and Conditions | Operating Grants | Biomedical | Musculoskeletal Health and Arthritis | Chicken Pox; Molecular Virology; Post-Herpetic Neuralgia; Shingles; Varicella Zoster Virus; Virus-Host Cell Interaction | Shingles is a debilitating disease that causes painful and disfiguring blistering skin lesions. In many afflicted individuals, pain continues for months or years following the illness in the form of post-herpetic neuralgia. Shingles is caused by varicella zoster virus (VZV). Initial infection with this virus causes chickenpox, following which the virus persists in the host in a latent form. However, in many individuals the virus will eventually reactivate causing shingles. This reactivation is associated with a weakened immune system, and thus is typically found with advancing age, as well as in immunosuppressed individuals. The availability of an attenuated chickenpox vaccine has resulted in a decrease in the incidence of this disease, and more recently an attenuated vaccine against zoster has entered the market, but in both cases efficacy is incomplete. In the context of an aging population, even with the recent vaccine advances, the impact of shingles on Canadians can be expected to remain a significant cause of long-term pain, particularly in older individuals. In order to develop new treatments for shingles, a better understanding of the interactions at the molecular level between the causative agent, VZV, and the host cell is required. VZV is a member of the neurotropic sub-family of herpesviruses, a group that also includes herpes simplex virus 1 (HSV-1). As with HSV-1, multiple steps in the life cycle of VZV take place within the nucleus of the cell, including the maintenance of the latent genome and subsequent reactivation from latency. Our objective in this pilot project is to begin to elucidate how VZV-induced modifications of the host cell nucleus contribute to efficient viral replication. The results from this project should contribute to a better understanding of the molecular mechanisms of VZV replication and reactivation, information that can then be exploited in the development of new treatment strategies for shingles. | 1 yr 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=163305&lang=en |
| 163307 | The Biomechanics of Skin Blistering Diseases: A Cellular and Biophysical Approach. | Fudge Douglas S | Fudge, Douglas S | University of Guelph | Ontario | Canada | 200802 | 90322.0 | Catalyst Grant: Skin Diseases and Conditions | Operating Grants | Biomedical | Musculoskeletal Health and Arthritis | Biomechanics; Biophysics; Epidermolysis Bullosa Simplex; Intermediate Filaments; Keratin; Skin | Epidermolysis Bullosa Simplex (EB) is a genetic disease characterized by blistering or erosion of the skin. Here we propose to study the physical basis and mechanisms of this disease. Mutations in a variety of structural proteins in skin can give rise to EB, but it is not known exactly how these defects weaken the skin. This proposal focuses on two components of skin cells that have been implicated in EB - keratin intermediate filaments (IF) and desmosomes. Keratin IFs are protein filaments that form a dense network in the cytoplasm and are believed to impart cells with mechanical strength. Mutations in keratin IF genes have been shown to lead to a form of EB known as EB Simplex (EBS). In EBS patients, the IF network in skin cells is defective, which is believed to make them mechanically fragile. Of course a network of keratin IFs alone does not guarantee mechanical strength - the filaments must be anchored to structures that are equally strong. Indeed, IFs are anchored in spot-weld like structures called desmosomes. Together, IFs and desmosomes link skin cells into a tough mechanical continuum. We will conduct two kinds of experiments using both wild type cells and cells expressing mutant keratin IF and desmosomal proteins. In the first, we will mechanically deform skin cells that are adhered to a deformable substrate and assess the effects on cell viability and the structure of the IF network. In the second set of experiments, we will investigate the biomechanics of wild type and mutant IFs using purified IFs. The results of these experiments will provide new insights into the mechanical function of IFs and desmosomes in skin, and the mechanisms by which defects in these structures can lead to human disease. They will also help us develop an in vitro model that we can use to evaluate the efficacy of potential treatments for this debilitating disease. | 1 yr 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=163307&lang=en |
| 163312 | Manipulating regulatory T cells to control inflammatory skin disease | Dutz Jan P | Dutz, Jan P | University of British Columbia | British Columbia | Canada | 200802 | 100000.0 | Catalyst Grant: Skin Diseases and Conditions | Operating Grants | Biomedical | Musculoskeletal Health and Arthritis | Autoimmunity; Dendritic Cell; Flow Cytometry; Regulatory T Cell; Ultraviolet Light | Inflammatory skin disease is common and often debilitating. Examples of chronic and debilitating skin conditions include psoriasis, vitiligo, alopecia areata and graft versus host disease. Regulatory T cells are powerfull inhibitors of inflammation. In this proposal, a team of clinicans and scientists will explore the function and manipulation of regulatory T cells to treat chronic skin disease. | 1 yr 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=163312&lang=en |
| 163317 | Modèles d'étude nouveaux et polyvalents produits par génie tissulaire pour l'analyse des cancers de la peau | Auger François A | Auger, François A | Université Laval | Québec | Canada | 200802 | 100000.0 | Catalyst Grant: Skin Diseases and Conditions | Operating Grants | Biomedical | Musculoskeletal Health and Arthritis | Cancers; Génie Tissulaire; Maladies De La Peau; Modèles In Vitro; Mélanomes; Peau | Les maladies de la peau devraient susciter davantage de recherches pour de nouveaux traitements. Les cancers de la peau, et en particulier les mélanomes, font partie des plus graves problèmes en dermatologie. Le fait que les cas de mélanomes semblent augmenter et qu'ils peuvent rapidement provoquer la formation de métastases rend ce type de cancer une cible importante pour la recherche médicale. Le processus par lequel des mélanomes se développent et la formation des métastases sont des processus complexes. La simple culture de cellules permet de décortiquer plusieurs éléments précis mais ne possède pas les autres éléments présents dans la peau. Les modèles animaux offrent un environnement expérimental complexe mais dans lequel il est parfois difficile de bien isoler l'effet des différents facteurs. Les substituts cutanés produits par génie tissulaire avec des cellules de peau humaine offrent une solution intermédiaire intéressante en créant un environnement tridimensionnel comportant les principaux éléments de la peau. Grâce à ce type de modèle plusieurs éléments critiques de maladies de la peau telles que le cancer et le psoriasis, par exemple, pourront être examinés. | 1 yr 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=163317&lang=en |
| 167487 | Can a mobile falls prevention clinic reduce the risk of falls in community dweling seniors? | Singh Sonia | Singh, Sonia; Scott, Vicky J | Fraser Health Authority (Surrey, BC) | British Columbia | Canada | 200803 | 113783.0 | Operating Grant: Demonstration Projects in Mobility in Aging | Operating Grants | Health systems / services | Aging | Cohort Study; Cost-Effectiveness; Falls And Injury Prevention; Mobile Clinic; Osteoporosis; Seniors | An estimated 30 percent of community dwelling individuals over 65 years of age fall at least once each year. Consequences of falls include fractures, head concussions, bruises, and lacerations. "Fear of Falling" results in restricted activity, increased dependency on others and a decrease in social interaction. The injuries associated with falls in the elderly account for over $1.0 billion in annual health care costs in Canada. This research study aims to determine if a Mobile Falls Prevention Clinic, traveling to seniors in their own community, would improve access to falls prevention services and prevent falls and falls-related injuries from occurring. Those seniors that agree to participate in the study will be followed for 12 months during which time they will all undergo the Mobile Falls Prevention Clinic Program. Each study participant will undergo a special falls risk assessment called the Physiological Profile Assessment during their Mobile Falls Prevention Clinic visit. This assessment will be repeated 12 months later. During the 12 month period after the clinic visit, study participants will keep a record of their falls and falls related injuries and check in with study personnel on a monthly basis. Study participants' medical records will be reviewed for details around falls and falls related injuries. A cost benefit analysis will take place alongside the study to determine if the Mobile Clinic format is a cost-effective way of delivering falls prevention services. The Mobile Falls Prevention Clinic has the potential to dramatically improve the lives of elderly seniors by reducing the risk of falling. Preventing falls and falls related injuries could help keep seniors mobile and community dwelling for as long as possible and prevent or delay long term institutional care. | 3 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=167487&lang=en |
| 167488 | Exercise in Older Adults: A demonstration and evaluation of the "Get Fit for Active Living" intervention. | Paterson Donald H | Paterson, Donald H; Fitzgerald, Clara; Speechley, Mark | Western University (Ontario) | Ontario | Canada | 200803 | 341383.0 | Operating Grant: Demonstration Projects in Mobility in Aging | Operating Grants | Social / Cultural / Environmental / Population Health | Aging | Behaviour Modification / Adherence; Delayed Catch-Up Research Design; Evaluation; Functional Fitness; Knowledge Translation; Physical Activity For Older Adults | Policies on physical activity for older adults tend to advocate even minor increases in daily physical activity, on the grounds that any is better than none. While this may be true, recent evidence suggests that minor increases in activity result in at most minor gains in health. To achieve full benefit of an active lifestyle, a more structured exercise/activity program is required. The program should consist of moderate and vigorous intensity aerobic activity for 30 minutes/day, 4-5 days/week to gain cardiorespiratory fitness, prevent functional decline, and strength and power exercises 2 days/week to maintain muscle mass and performance. Thus, there is a disconnect between best practices, and what is believed by most to be the type and amount of physical activity required by older adults to engender health, functional fitness, and independent living. Many people begin exercising each year. In spite of good intentions, a lot of them do not continue to exercise. Recognizing this problem, the Canadian Centre for Activity and Aging (CCAA) developed an 8-week intervention("Get Fit for Active Living", GFAL) that educates older adults about the importance of exercise, and provides experience in developing an exercise routine, which in turn motivates them to maintain the lifestyle. The rationale was that older adults need "experiential learning" while they develop an exercise program, and that with gains in fitness the older adults would experience less fatigue in daily activities and maintain a more active lifestyle. The CCAA has trained over 40 facilitators of this program nationally, and initial pilot work suggests the program indeed fosters adherence to an active lifestyle. Over 3 years, this project will formally evaluate the GFAL program by studying its effect on the functional fitness, quality of life, and enhanced independence of 300 older adult "Meals on Wheels" volunteers across Canada, and how effective the uptake of the program is at the community level. | 3 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=167488&lang=en |
| 167489 | Entraînement physique et stimulation cognitive pour améliorer la mobilité des personnes âgées fragiles | Bherer Louis | Bherer, Louis | CIUSSS du Centre-Sud-de-l'Île-de-Montréal (Montréal, Québec) | Québec | Canada | 200803 | 189950.0 | Operating Grant: Demonstration Projects in Mobility in Aging | Operating Grants | Clinical | Aging | Activité Physique; Cognition; Mobilité; Vieillissement | L'objectif principal de ce projet de recherche est d'évaluer l'efficacité d'un programme d'entraînement physique combiné à des séances de stimulation cognitive, pour améliorer les capacités physiques et cognitives associées à la mobilité. Le projet vise aussi à vérifier l'impact de ces interventions sur la qualité de vie des personnes âgées légèrement et modérément fragiles. Des personnes âgées seront suivies au Centre de recherche de l'Institut universitaire de gériatrie de Montréal et évaluées par des cliniciens (gériatres, physiothérapeutes, psychologues) qui souhaitent prescrire de l'activité physique à ces personnes. Il est attendu que ce projet de recherche permette une évaluation scientifique rigoureuse de l'efficacité de ces prescriptions et évalue la faisabilité de la mise en place des programmes d'activités physiques et cognitives pour les personnes âgées fragiles. | 3 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=167489&lang=en |
| 167490 | A Inpatient Rehabilitation Model of Care Targeting Patients with Cognitive Impairment: A demonstration project | McGilton Katherine S | McGilton, Katherine S | Toronto Rehabilitation Institute-UHN | Ontario | Canada | 200803 | 362915.0 | Operating Grant: Demonstration Projects in Mobility in Aging | Operating Grants | Health systems / services | Aging | Demonstration Project; Non-Equivalent Quasi-Experimental Design; Rehabilitation Of Patients With Cognitive Impairment; Rehabilitation Of Patients With Hip Fractures | Hip fractures are a danger to an individual's mobility, independence and ability to live in the community. When patients have a cognitive impairment (such as dementia or delirium) they do not recover as well or go back to their homes as often as those patients who do not have a cognitive impairment. Therefore, our team developed a rehabilitation model to care for patients with hip fractures, and specifically for those patients with CI. The model of care is called the Patient Centred Rehabilitation Model of Care (PCRM-CI). This 3 year study will focus on comparing the new model with usual rehabilitation care. This study will also focus on understanding the factors that could influence the use of the model on new rehabilitation units. We will collect data in 2 hospitals, 70 patients receiving the usual care and 70 patients receiving the care in the new model. We will invite 70 staff and their unit managers as well. This study will help policy makers to use research findings to make better decisions about care of older Canadians. | 3 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=167490&lang=en |
| 168565 | Frequency-Selective MRI in Regenerative Medicine | Cunningham Charles H | Cunningham, Charles H | Sunnybrook Research Institute (Toronto, Ontario) | Ontario | Canada | 200709 | 400000.0 | Peter Lougheed/CIHR New Investigator Canada's Premier Young Researcher | Salary Programs | Biomedical | Circulatory and Respiratory Health | Cell Tracking; Contrast Agents; Magnetic Resonance Imaging; Metabolism; Molecular Imaging; Regenerative Medicine | Coronary artery disease, leading to chest pain and heart attacks, is the leading cause of death in the developed world. The damaged heart muscle is replaced with scar tissue resulting in diminished ability to pump blood and culminating in heart failure in a third of all patients, even with all the treatments provided by modern medicine. Based on positive results in small animals, there is hope that cell-based therapies using transplants of progenitor cells, such as bone marrow derived in stem cells, will provide a means to reduce the incidence of heart failure by repairing the damaged heart tissue. In research towards this goal, methods for following the location and studying the activity of these transplanted cells are of utmost importance. Magnetic resonance imaging has shown a great deal of promise for tracking the location of stem cells non-invasively. In the proposed research plan, a novel method for imaging stems cells such that the signal is bright (as opposed to dark with conventional methods) is developed towards application in the clinic. In a second project component, MRI of hyperpolarized carbon-13, which enables the direct imaging of metabolism using an MRI machine, is studied. This new method is proposed for studying cellular metabolism in and around damaged heart muscle to better plan and evaluate regenerative therapy. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=168565&lang=en |
| 168880 | FIRST for Depression in an EAP: Feasibility of Intervention Research on Stepped-care Treatment for Depression in an Employee Assistance Program. | Lam Raymond W | Lam, Raymond W | University Hospital (U.B.C.) | British Columbia | Canada | 200807 | 66361.0 | Catalyst Grant: Planning & Develop. in Mental Hlth & Addiction in the Workplace | Operating Grants | Clinical | Neurosciences, Mental Health and Addiction | Cognitive Behaviour Therapy; Depression; Employee Assistance Programs; Qualitative Methods; Rating Scales; Workplace | Clinical depression and anxiety in employees, managers and executives (workplace depression) is a significant burden to society from both human resource and economic viewpoints. Depression is now a leading cause of absenteeism, short-term and long-term disability, and also contributes significantly to "presenteeism" in affected workers. Despite the impact of clinical depression on workplaces, there is little information on the most effective interventions for workers struggling with depression. Employee and family assistance programs (EAPs) are often the "first line of defence" for employees coping with stress, depression and anxiety. Our study, "FIRST for Depression in an EAP", will focus on screening and early intervention strategies in EAP clients with clinical depression and anxiety. We will pilot test novel types of treatment (for example, computer-assisted or telephone-delivered counseling) in an EAP to find out how acceptable and how satisfactory are these methods for clinicians and clients. We will also address some of the barriers to conducting intervention research in a business and clinical setting such as an EAP. The results from "FIRST for Depression in an EAP" will allow us to plan rigorous studies to evaluate interventions within EAPs. The results will also provide new information on the clinical and productivity outcomes of clients with depression and anxiety using EAP services. | 1 yr 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=168880&lang=en |
| 168881 | Mindfulness-based Cognitive Therapy for the prevention of depressive relapse in the workplace | Lau Mark A | Lau, Mark A | University of British Columbia | British Columbia | Canada | 200807 | 73340.0 | Catalyst Grant: Planning & Develop. in Mental Hlth & Addiction in the Workplace | Operating Grants | Clinical | Neurosciences, Mental Health and Addiction | Depression; Employee Assistance Program; Mindfulness-Based Cognitive Therapy; Relapse Prevention; Telehealth; Workplace | Depression is among the most costly of all health problems to employers. This is particularly true for the health service sector, which typically employs mostly women as depression is twice as prevalent for women as for men. As a result, these workplaces can demonstrate higher than normal prevalence rates for depression. For example, in a recent health survey of 10,000 employees of the Provincial Health Services Authority (PHSA), which operates highly specialized health services in British Columbia, over 12% were likely to be experiencing depression. Importantly, approximately 50% of individuals who recover from an initial episode of depression will develop a second episode, and for those with a history of two or more episodes, the relapse/recurrence risk increases to 70-80%. To better manage and prevent depression at PHSA, mindfulness-based cognitive therapy (MBCT) has been approved as part of PHSA's Workplace Mental Health & Addiction Strategy to reduce the risk of depressive relapse. MBCT is a group based treatment that has been shown to be effective in preventing depressive relapse. However, it remains to be determined how to effectively deliver MBCT in the workplace as some employees may not be interested in participating in a group with other co-workers. Thus, the goal of this proposal is to evaluate employee preferences and the feasibility of offering MBCT as delivered in four different formats: (1) group MBCT; (2) group MBCT via the internet; (3) individual MBCT; and, (4) individual MBCT via telephone. In addition, we will evaluate the effectiveness of an MBCT training program for Employee Assistance Program practitioners who will be recruited and trained to provide MBCT. Our proposed work will help to determine which MBCT delivery format(s) is the most promising for use in the workplace and help prepare our research team/workplace partnership for future studies of implementing MBCT to prevent depressive relapse and improve workplace outcomes. | 1 yr 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=168881&lang=en |
| 168882 | PREDICTORS OF STRESS AND TRAUMA RESPONSES TO HIGH IMPACT EVENTS IN POLICE DISPATCHERS | Leblanc Vicki R | Leblanc, Vicki R; Regehr, Cheryl | University of Toronto | Ontario | Canada | 200807 | 48340.0 | Catalyst Grant: Planning & Develop. in Mental Hlth & Addiction in the Workplace | Operating Grants | Social / Cultural / Environmental / Population Health | Neurosciences, Mental Health and Addiction | Cortisol; Mental Health; Police Dispatchers; Post-Traumatic Stress Symptoms; Predictor Variables; Stress | Emergency services work is characterized by high stress situations requiring immediate intervention and by exposure to distressing events that are outside the experience of the general public. Dispatchers must cope with a rapid succession of emergency calls, interact with highly distressed callers often over a prolonged period of time, and coordinate interprofessional communications in order to achieve positive outcomes. Furthermore, dispatchers are not physically present at the site of an emergency; they often report feeling isolated and powerless to assist during the emergency and are generally unaware of the resolution of the event. The proposed research project is a pilot study aimed at generating preliminary data regarding the interactions of mental health disruptions, mediating factors, stress responses and performance in an understudied population that is regularly exposed to salient stressors. In this study, participating dispatch workers will be required to respond to a simulated 9-1-1 call from a member of the public. A number of psychosocial and physical stressors will be added to the scenarios. The participants¿ stress responses (subjective and physiological) will be assessed. Furthermore, a number of potential predictor variables will be assessed in order to determine whether they mediate responses and performance during acute events. The proposed project represents the first study in a developing program of research aimed at understanding the effects of acute stress and trauma on police dispatchers. The findings of this study will be used to inform the design of subsequent research projects aimed at examining how these factors of interest play out in real world scenarios. Furthermore, the results of this project will be crucial in guiding the development of interventions and policies for the support and training of those individuals who routinely encounter acutely stressful events. | 1 yr 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=168882&lang=en |
| 168885 | Workplace reintegration of Veterans with mental disorders | Pedlar David J | Pedlar, David J | University of Prince Edward Island (Charlottetown) | Prince Edward Island | Canada | 200807 | 80000.0 | Catalyst Grant: Planning & Develop. in Mental Hlth & Addiction in the Workplace | Operating Grants | Health systems / services | Neurosciences, Mental Health and Addiction | Depression; Mental Health; Military Workforce; Operational Stress Injuries; Post Traumatic Stress Disorder; Veteran | Workplace Reintegration of Veterans with Mental Disorders Mental health has special significance in the Canadian military and Veteran (former military) populations. For example, the rate of depression among regular Canadian Forces members is double that of the general population. Military service is demanding both physically and emotionally, and mental illness may be a consequence of military service. Mental disorders are associated with premature discharge from the military. Furthermore, reintegrating into the civilian workplace is difficult for Veterans in Canada, Britain, and the United States. The primary objective of this proposal is to build a team of experts in workplace reintegration difficulties in Veterans with mental disorders. Team building is the first phase of an anticipated research program that will provide an understanding of successful reintegration, determined by the interplay of workplace, compensation, health care, and personal factors. Veterans are an understudied population of about 1 million Canadians. Building this team of experts will provide the first opportunity to expand knowledge on the impact of mental health on workplace reintegration of Veterans. This research team has the potential to 1) direct policy development, as programs for Veteran vocational rehabilitation are evaluated and adjusted, 2) establish important research targets in Veteran workplace mental health, 3) pave the way for intervention research that aims to increase successful reintegration of Veterans into civilian life. We owe a special duty to those who have made sacrifices while serving Canada. | 1 yr 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=168885&lang=en |
| 169068 | National network for characterization of influenza virus evolution and antiviral drug susceptibility | Boivin Guy | Boivin, Guy | Université Laval | Québec | Canada | 200806 | 0.0 | Catalyst Grant: Pandemic Outbreak Team Leader | Operating Grants | Biomedical | Infection and Immunity | Antiviral; Influenza Virus; Phylogeny; Resistance; Viral Evolution | Influenza A viruses evolve constantly and rapidly leading to seasonal flu epidemics and occasional but devastating flu pandemics. There is thus a need to rapidly identify new emerging influenza strains for rapid development of effective influenza vaccines. In addition, there has been a recent and important increase of influenza resistance to the only two classes of antiviral agents available (adamantanes and neuraminidase (NA) inhibitors) which limit treatment/prophylactic opportunities for infected patients and their contacts. In this research, we propose to set up a national network for a comprehensive and real-time evaluation of influenza virus evolution and for global antiviral suceptibility assessment. In brief, a panel of influenza A viruses will be collected at 4 geographically-representative Canadian virology laboratories during a major influenza outbreak or in the early phase of a pandemic. The molecular (NA and hemagglutinin (HA) gene sequencing) and antigenic properties of these viruses will be analyzed at a central laboratory. Based on sequence alignments, phylogenetic trees will be constructed to assess viral evolution over time. Similarly, phenotypic (plaque and enzymatic assays) and genotypic methods will be used to evaluate viral susceptibility or resistance to available antiviral agents. All results will be rapidly transmitted to provincial and national public health authorities. At term, this integrated network will improve public health control measures with more rationale use of antiviral agents and rapid design of effective vaccines in the case of major influenza outbreaks or pandemics. | 1 yr 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=169068&lang=en |
| 169070 | Catalyst Grant: Pandemic Outbreak Team Leader in Mathematical Modeling | Pourbohloul Babak | Pourbohloul, Babak | University of British Columbia | British Columbia | Canada | 200806 | 0.0 | Catalyst Grant: Pandemic Outbreak Team Leader | Operating Grants | Social / Cultural / Environmental / Population Health | Infection and Immunity | Contact Network Epidemiology; Human/Avian Influenza; Mathematical Modeling; Pandemic Preparedness Planning; Public Health; Transmission Dynamics | The threat posed by the emergence of the highly pathogenic strain of influenza A has been met with an abundance of preemptive scientific research to prepare for a pandemic. However, it is equally important that Canada¿s top researchers are accessible at the advent of a pandemic to adapt and develop public health measures as the pandemic progresses. The objective of this application is to bring together the required leadership and expertise to create a predictive integrated framework that will strengthen Canada¿s pandemic response both at the beginning, as well as throughout the duration of a pandemic. The threat posed by the emergence of the highly pathogenic strain of influenza A has been met with an abundance of preemptive scientific research to prepare for a pandemic. However, it is equally important that Canada¿s top researchers are accessible at the advent of a pandemic to adapt and develop public health measures as the pandemic progresses. The objective of this application is to bring together the required leadership and expertise to create a predictive integrated framework that will strengthen Canada¿s pandemic response both at the beginning, as well as throughout the duration of a pandemic. This application will yield a national network that leverages tremendous expertise in EID modeling and positions Canada at the forefront in terms of outbreak research and rational planning for EIDs. With the latest mathematical techniques and the most advanced computational technologies at their disposal, this team, under the proposed leadership, can significantly improve Canada¿s response to any potential threat from emerging infections, both nationally and internationally. | 1 yr 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=169070&lang=en |
| 169136 | hereditary cancers (genetics) such as VHL, FAP, | Green Jane S | Green, Jane S | Memorial University of Newfoundland | Newfoundland and Labrador | Canada | 200805 | 50000.0 | Knowledge Translation Prize | Operating Grants | 1 yr 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=169136&lang=en | ||||
| 169139 | late-life suicide prevention toolkit | Heisel Marnin J | Heisel, Marnin J | Western University (Ontario) | Ontario | Canada | 200806 | 50000.0 | Betty Havens Prize | Operating Grants | 1 yr 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=169139&lang=en | ||||
| 169140 | Action Schools! childhood inactivity and obesity | Mckay Heather A | Mckay, Heather A | University of British Columbia | British Columbia | Canada | 200805 | 50000.0 | Knowledge Translation Prize | Operating Grants | 1 yr 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=169140&lang=en | ||||
| 169144 | Tele-ophthalmology to improve access to ophthalmologic care in remote areas | Tennant Matthew T | Tennant, Matthew T | University of Alberta | Alberta | Canada | 200805 | 100000.0 | Knowledge Translation Prize | Operating Grants | 1 yr 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=169144&lang=en | ||||
| 169936 | Down Syndrome Research Foundation | Mckenna Dawn | Mckenna, Dawn | Down Syndrome Research Foundation (Burnaby, BC) | British Columbia | Canada | 200806 | 25000.0 | Partnership Award | Operating Grants | 1 yr 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=169936&lang=en | ||||
| 170018 | Physician billing costs attributable to ambiguous genetic tests | Speechley Mark | Speechley, Mark; Adams, Paul C | Western University (Ontario) | Ontario | Canada | 200803 | 22788.0 | Operating Grant: Genetics (Ethics, Law and Society) | Operating Grants | Social / Cultural / Environmental / Population Health | Genetics | Ambiguous Results; Genetic Tests; Hemochromatosis; Iron Overload; Physician Billings; Social Impact | The use of genetic tests to identify people who face an increased disease risk is growing in Canada. The social marketing of gene tests contains two misleading messages: i) the prices for tests are low and will continue to decline; and ii) gene test results will allow doctors to make highly accurate individual diagnoses and treatment decisions. These messages are misleading because the price of tests alone ignores social costs such as additional health care utilization, and the clinical utility of most gene tests is far from definitive. While the message implies genetic certainty, in fact many gene tests will produce ambiguous results. When combined with phenotypic (i.e. blood) tests, many people will fall in abiguous categories. In the case of hereditary hemochromatosis, twelve different combinations result. For two of these combinations, there is sufficient medical evidence to provide people with clear advice to follow-up with their doctor. A third combination results in no detectable abnormalities, and clear advice that no further follow-up is warranted. The remaining nine combinations, however, are ambiguous in terms of specific disease risk and appropriate follow-ups. This study is set up to examine changes in the number and type of visits to physicians as well as increased health care costs in those who received ambiguous screening results in a study of 20,000 Canadians. | 1 yr 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170018&lang=en |
| 170020 | Defining Stakeholders Rights and Obligations in Population Biobanks Through Material Transfer Agreements (MTAs) | Knoppers Bartha M | Knoppers, Bartha M | Université de Montréal | Québec | Canada | 200803 | 18930.0 | Operating Grant: Genetics (Ethics, Law and Society) | Operating Grants | Biomedical | Genetics | Ethics; Genetics; Law; Material Transfer Agreement (Mta); Population Biobanks; Stakeholders | The implementation of DNA repositories has brought to the forefront certain ethical and legal challenges surrounding genomic research. One such challenge is related to the regulation and control of the ethical and legal obligations of researchers who will utilize these research infrastructures. This project will investigate the possibility for population biobanks to use Material Transfer Agreements (MTAs) as a regulatory tool in promoting the rights of various stakeholders. In the absence of specific legislation addressing the ethical and legal obligations of researchers using population based research infrastructures, MTAs may be able to provide a flexible and efficient alternative. Even though MTAs are widespread within the research sector, they need to be specifically tailored to issues relevant to population biobanks. Thus, this study will focus on how publicly funded infrastructures (DNA repositories) can use a Uniform Material Transfer Agreement (UMTA) to: 1) better define and respect the rights of participants, funding agencies and potential researchers; 2) preserve the open-source approach of publicly funded infrastructures; 3) preserve patentability and licensing of resulting intellectual property; 4) clearly define research limits in light of public purpose and the participant's informed consent; 5) establish national and international transfer modalities for biological samples and data; and 6) define related risks and responsibilities. A proper analysis of these aspects may reveal that MTAs can, at least provisionally, in the absence of specific legislation, be used as a flexible and efficient tool in the context of research infrastructures improving predictability, public protection (and incidentally confidence), decreasing negotiation delays and setting important standards in the field. It is hoped that these proposed standards will influence the private sector as well. | 1 yr 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170020&lang=en |
| 170021 | Environmental Scan and Stakeholder Consultation on Electronic Personal Health Records in Canada | Archer Norman P | Archer, Norman P; Mckibbon, Kathleen Ann; Straus, Sharon E; Willison, Donald J | McMaster University | Ontario | Canada | 200803 | 75000.0 | Operating Grant: Genetics (Ethics, Law and Society) | Operating Grants | Health systems / services | Health Services and Policy Research | Chronic Care; Elderly Care; Health Self-Management; Home Healthcare; Online Accessibility; Personal Health Records | The Canadian healthcare system is moving towards a reduction of operating cost by an increased emphasis on caring for the elderly and patients with chronic diseases of all ages at home instead of institutional care. This requires an increase in the care provided to patients through homecare nursing, personal support workers, and informal care providers (e.g. relatives). Such care might be provided more effectively if care providers and patients were given online access to the patient's medical records and to educational support in the home environment. This would mean linking providers with online systems that provide access to relevant records maintained by the patient's doctor, hospital records, pharmacy records, etc. Records provided to the patient in this way are called electronic personal health records (ePHRs). Such an approach would parallel the announced philosophy of the Canadian healthcare system to provide electronic health records for all Canadian patients, but with a further extension to patients themselves and their care providers. Given the complex nature of the computer systems involved, this is not a simple task. The objective of this proposal is to: 1) carry out a review of ePHRs that summarizes existing implementations and relevant research, and report on benefits and barriers to their use, 2) develop techniques (questionnaires, etc.) that can be used to gather information from a sample of Canadian healthcare practitioners, providers, and patients on their views of ePHRs; gather information, using these techniques, that can help to understand what form ePHRs should take and what education is needed to make use of them by caregivers and their patients, and 3) develop a priority list of the research gaps and capacity needs that have been identified, using information gathered in this study. | 1 yr 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170021&lang=en |
| 170056 | Understanding simultaneous polysubstance use: Patterns and consequences of mixing substances in illicit drug users. | Barrett Sean P | Barrett, Sean P | Dalhousie University (Nova Scotia) | Nova Scotia | Canada | 200810 | 96600.0 | Catalyst Grant: Prevention and Treatment of Illicit Substance Use | Operating Grants | Clinical | Neurosciences, Mental Health and Addiction | Addiction; Drug Abuse; Drug Related Harms; Illicit Susbtance Use; Polysubstance Use; Treatment Outcome | One issue that may hinder our understanding of illicit drug addiction is the tendency for drug users to administer multiple substances at a time, a phenomenon known as simultaneous polysubstance use (SPU). High rates of SPU have been documented across users of various illicit substances, and evidence suggests that simultaneous use of more than one substance can alter subjective and behavioural responses to the drugs and increase the harmful consequences of use. However, traditional models for assessing, diagnosing and treating substance use disorders tend to focus on problems associated with individual substances in isolation from one another. The principal applicant has recently developed a structured interview technique to assess patterns of SPU including details regarding order, amount, type and route of administration of all substances administered on specific substance use occasions. Preliminary results from studies using this method showed that participants were able to reliably recall such details and that certain combinations of substances followed identifiable patterns of co-administration. However, because these studies did not assess the presence or absence of substance related disorders or the harmful consequences of multiple substance use, the clinical significance of these findings remains unknown. The proposed research will examine patterns of SPU in various illicit substance-dependent populations and determine how SPU patterns are associated with substance-related disorders and harms. | 1 yr 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170056&lang=en |
| 170057 | Neurobiological basis of the effects of methamphetamine (Crystal Meth): a behavioural and electrophysiological study. | Dumont Eric C | Dumont, Eric C | Queen's University (Kingston, Ontario) | Ontario | Canada | 200810 | 20750.0 | Catalyst Grant: Prevention and Treatment of Illicit Substance Use | Operating Grants | Biomedical | Neurosciences, Mental Health and Addiction | Bed Nucleus Of The Stria Terminalis; Brain Slices; Methamphetamine (Crystal Meth); Patch-Clamp; Self-Administration; Synaptic Transmission | In spite of intense efforts in research, as well as clinical and field interventions to prevent and treat drug addiction, this health problem is still devastating and worse, is still growing. In particular, methamphetamine (Crystal Meth) is relatively easy and cheap to synthesize: the recipe is available on the internet and ingredients can be purchased over the counter at the local pharmacy. Most current therapies provide short-term solutions to help detoxification and support abstinence. However, the main problem in treating or preventing addiction is the long lasting, even permanent, neuronal alterations produces by drugs of abuse. These long-lasting alterations underlie the aggravating properties of several risk factors and the difficulty of remaining abstinent after detoxification. My research program investigates the neuronal basis of the long term and somehow permanent neuronal modifications induced by drugs of abuse. This particular research projects will determine the effects of Crystal Meth on synaptic transmission combining behavioural testing of methamphetamine self- administration in rodents with patch-clamp recordings in brain slices. The long term objective is to help in developing therapies aimed at reversing these neuronal modifications and hope to permanently occlude susceptibility to develop addiction or to relapse albeit sincere efforts to refrain. | 1 yr 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170057&lang=en |
| 170246 | Characterization of the elaborate interplay between HIV-1 and dendritic cells | Tremblay Michel J | Tremblay, Michel J | Université Laval | Québec | Canada | 200809 | 784445.0 | Operating Grant | Operating Grants | Biomedical | Infection and Immunity | Aids; Cellular Biology; Confocal; Dendritic Cells; Hiv-1; Molecular Biology | It is generally thought that dendritic cells are playing a pivotal role in HIV-1 transmission as they serve as the first potential targets for virus infection. The central objective of our work is to illuminate the intricate relationships between HIV-1 and dendritic cells. An improved understanding of the elaborate relationships between HIV-1 and dendritic cells is needed because it can result in the development of more appropriate and efficient preventive/therapeutic measures directed at a better control of HIV-1. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170246&lang=en |
| 170247 | Control of sensory neuron development | Chen Hsiao-Huei | Chen, Hsiao-Huei | Ottawa Hospital Research Institute | Ontario | Canada | 200809 | 300000.0 | CIHR New Investigator | Salary Programs | Biomedical | Neurosciences, Mental Health and Addiction | Electrophysiology; Experimental Embryology; Immunohistochemistry; Molecular Biology; Neurogenesis; Transgenic Mice | Sensory neurons are frequently lost in patients with cancer, diabetes or HIV infection. Optimally, cell based therapies to selectively replace the missing sensory neurons will require knowledge of the molecular pathways controlling sensory neuron development and function. This knowledge may also be useful to treat other sensory neuropathies affecting hearing and vision. This proposal is directed at elucidating the signaling and transcription pathways that control development and function of sensory neurons that detect muscle stretch in the "knee-jerk" reflex. We have discovered a protein that is essential for these neurons to develop and survive. Using mouse models that lack this protein, we will dissect how this protein works to control sensory neuron development. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170247&lang=en |
| 170252 | Delineating the role of epigenetic modification of histones in establishing tissue specific gene expression. | Dilworth Jeffrey J | Dilworth, Jeffrey J | Ottawa Hospital Research Institute | Ontario | Canada | 200809 | 686661.0 | Operating Grant | Operating Grants | Biomedical | Human Development, Child and Youth Health | Chromatin; Development; Epigenetics; Gene Expression; Myogenesis; Stem Cells | The different cell types within the human body all possess an identical DNA content. However, each cell-type has a specific subset of genes that it expresses which gives rise to its identity. Once a cell becomes committed to a cell lineage, a gene expression profile is established that is put into a memory that can then be passed on to daughter cells. This cellular memory is established through epigenetic modification of chromatin, and is mediated by the polycomb and trithorax groups of proteins. In this proposal, we plan to examine how specific cell types decide which genes are going to be marked by polycomb and trithorax group proteins. Using muscle cell development as a model system, we will examine the role of transcriptional regulators in targeting trithorax group proteins to muscle specific genes. Information gained through these studies will permit us to better understand how different cell types are established during development. This knowledge will allow us to take an informed approach to differentiating cells, and thus facilitate the development of efficient stem cell therapies. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170252&lang=en |
| 170284 | AHF-EM: Acute Heart Failure - Emergency Management | Ezekowitz Justin A | Ezekowitz, Justin A | University of Alberta | Alberta | Canada | 200809 | 300000.0 | CIHR New Investigator | Salary Programs | Health systems / services | Circulatory and Respiratory Health | Acute Heart Failure; Epidemiology; Pre-Hospital Care | Heart failure is the inability of the heart to pump adequate blood and oxygen to supply the needs of the body. Patients with heart failure have difficulty breathing, get tired easily and often have swollen legs and extra fluid in the lungs. In Canada, about 500,000 people have heart failure. Heart failure is a condition that results in frequent visits to clinic, emergency room visits, hospital stays, and has a high risk of death. Patients with heart failure have been well studied in the clinic, and when they are very sick (in hospital). However, patients that are getting sicker and need urgent attention have not been studied. They are often said to have 'acute heart failure'. This includes those needing an ambulance to take them to the emergency room. This group of patients is very important as they need urgent diagnosis, treatment, and a decision if they need to stay at the hospital. Currently, one third of patients with acute heart failure are sent straight home, and these patients are at high risk of needing urgent care again, and soon. This study will describe what happens to patients with heart failure during these first few hours of care, and in the next 3 months. By understanding how these patients are cared for, and how decisions are made, improvements to the system and potential treatments can be developed. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170284&lang=en |
| 170291 | Biomarkers of Disease Progression in Parkinsonism: Magnetic Resonance Imaging and Spectroscopy | Martin W.R. Wayne | Martin, W.R. Wayne | University of Alberta | Alberta | Canada | 200809 | 905080.0 | Operating Grant | Operating Grants | Biomedical | Neurosciences, Mental Health and Addiction | Gait Analysis; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Parkinson'S Disease; Surrogate Markers | Parkinson's disease (PD) is a progressive neurological disorder that affects the means by which the brain controls movement. Treatments that are currently available are reasonably effective at improving the symptoms in mildly to moderately affected individuals although some features associated with disease progression, such as impaired gait and balance, often do not respond well to medication. Current treatments do not alter the progressive nature of the underlying disease process. In order to evaluate the efficacy of new strategies to slow progression and to learn more about the gait changes associated with PD, we propose evaluating techniques that use magnetic resonance (MR) imaging and spectroscopy to measure the changes in the brain that occur in this disorder. These studies will be performed in the Movement Disorders Clinic at the Glenrose Rehabilitation Hospital and at the Peter S. Allen MR Research Centre at the University of Alberta. We will correlate the changes observed on magnetic resonance scans with the clinical changes in movement that we detect in the same patients, paying particular attention to changes in gait patterns. We will also correlate these changes with those seen on positron emission tomography (PET) scans, to be done on many of the same patients at the University of British Columbia in Vancouver. Our goal is to develop a new tool that can be used to evaluate disease progression in Parkinson's and to use this tool to assess the changes in the brain that occur in very early disease and in conjunction with worsening gait and movement problems. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170291&lang=en |
| 170324 | Access to and Quality of Cardiac Care for First Nations People | Hemmelgarn Brenda R | Hemmelgarn, Brenda R | University of Calgary | Alberta | Canada | 200809 | 215875.0 | Operating Grant | Operating Grants | Clinical | Indigenous Peoples' Health | Aboriginal People; Cardiovascular Disease; Health Services Research; Quality Of Care | Cardiovascular disease (CVD) is becoming more common among the First Nations population in Canada, resulting in an increasing burden of illness and death. Hospital admission rates for CVD are stable or declining for the Caucasian population, while they are steadily increasing for the First Nations population. In addition mortality secondary to CVD is also increasing in the First Nations population, with CVD the leading cause of death in this patient population. Reasons for the increasing burden of CVD among the First Nations population are not entirely clear, although factors including access to specialized cardiac care and procedures, as well as quality of cardiac care, have been suggested as contributing. No studies have been undertaken to determine if there are differences in access to and quality of cardiac care for First Nations compared to non-First Nations people. This study will determine if differences in cardiac care exist for First Nations compared to non-First Nations people by exploring access to specialized cardiac care and invasive cardiac procedures. It will also begin to address issues of quality of care by looking at differences in markers of quality care aimed at reducing the risk of vascular disease. | 3 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170324&lang=en |
| 170339 | Regulation of DNA replication | Brown Grant W | Brown, Grant W | University of Toronto | Ontario | Canada | 200809 | 623515.0 | Operating Grant | Operating Grants | Biomedical | Cancer Research | Cancer; Cell Cycle; Dna Replication; Genomic Instability; Yeast Molecular Biology | Before a cell can grow and divide it must duplicate its DNA. In this way, when a cell divides to form two daughter cells, each of the daughters will receive the full complement of genes required for its survival. We are studying how cells determine when to duplicate their DNA, how they sense whether their DNA is fully duplicated, and how they prevent cell division until this duplication is complete. These control pathways are critical for normal cell growth, and are frequently subverted in cancerous cells. When these controls fail to function cells can grow and divide in inappropriate locations, and can ignore the signals that cause normal cells to cease dividing. We hope that by understanding these pathways we can learn how they misfunction in cancerous cells. Critical elements of these pathways represent targets for drugs to block inappropriate cell growth and markers for inappropriate growth, both of which might one day be used in treating cancers. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170339&lang=en |
| 170340 | Elucidation of novel mechanisms of glucagon action | Drucker Daniel J | Drucker, Daniel J | Lunenfeld-Tanenbaum Research Institute (Toronto) | Ontario | Canada | 200809 | 737930.0 | Operating Grant | Operating Grants | Biomedical | Nutrition, Metabolism and Diabetes | Intestine; Pancreas; Peptide Hormones; Receptors | Glucagon is a hormone secreted from the pancreas that together with insulin, controls levels of blood sugar through actions on the liver. Excess glucagon action in diabetic subjects underlies the inappropriate increase in blood glucose observed in diabetic subjects-hencing reducing glucagon action is a major goal for development of new agents to treat type 2 diabetes. The proposed studies analyze the consequences of attenuating glucagon action in mice with genetic disruption of the glucagon receptor. The Results of these studies are expected to extend our knowledge about how glucagon works, and to inform us about the likely safety and efficacy of new drugs used to block glucagon action for the treatment of diabetes. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170340&lang=en |
| 170359 | Investigation of Pulsed Radiation Effects on RF Coils for Integrated MRI-Linac Project | Rathee Satyapal | Rathee, Satyapal; Fallone, Biagio G | Alberta Health Services | Alberta | Canada | 200809 | 263007.0 | Operating Grant | Operating Grants | Biomedical | Cancer Research | Image Guided Radiation Therapy; Magnetic Resonance Imaiging; Monte Carlo Simulation; Mri-Linac; Radiation Effects On Rf Coils; Radiation Therapy | Nearly half of the cancer patients will receive radiation therapy for their treatment. Image guided radiotherapy promises to precisely align the diseased volume with the radiation beams in real time, and it requires three dimensional imaging of the patient in treatment position regularly during the course of radiation therapy. The precise alignment of the patient with the radiation beams, in real time, will greatly eliminate the amount of healthy tissue which is unnecessarily irradiated in order to ensure accurate radiation dose delivery to the tumor that could move day to day due to patient setup and during the treatment due to involuntary motion. The ideal imaging system would specifically depict the tumor in addition to the normal patient anatomy even during the activation of the treatment beam using no extra radiation dose to the patient. A magnetic resonance imaging system integrated with a radiation therapy treatment linac holds a great promise to satisfy all these requirements. At Cross Cancer Institute, we are developing an integrated magnetic resonance imaging linac system. In such a system, the radiofrequency coils that are used to form magnetic resonance image will be irradiated. The present proposal aims to investigate various effects of short, intense radiation pulses of linac on the operation of radiofrequency coils. In particular, we will investigate the transient signal generated in radiofrequency coils due to radiation as a function of instantaneous dose rate, coil configuration, type of holding material for the coil. We will also investigate the degradation in the coil performance related to magnetic resonacne imaging as a function of accumulated radiation dose. In addition, the effect of placing the coil around or on the patient's skin on the radiation dose received by patient's skin will be investigated. The successful completion of this project will allow us to optimize the coil design for MRI linac project. | 3 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170359&lang=en |
| 170364 | Understanding the role of the mitochondrial rhomboid protease in membrane dynamics | Mcquibban George A | Mcquibban, George A | University of Toronto | Ontario | Canada | 200809 | 690225.0 | Operating Grant | Operating Grants | Biomedical | Genetics | Dominant Optic Atrophy; Drosophila; Genetics; Membrane Dynamics; Mitochondria; Yeast | Mitochondria are extremely dynamic organelles undergoing constant double membrane fusion and fission reactions. The control and mechanisms involved to regulate this activity are currently of great interest in both the health and the death of the cell. We have discovered the key action of the mitochondrial rhomboid protease in regulating membrane fusion. Rhomboids are highly conserved intramembrane proteases that process initially membrane tethered substrates. We have now identified three important substrates for the mitochondrial rhomboid: Mgm/OPA; a dynamin-related protein, Omi/HtrA2; a mitochondrial targeted protease, and Pink1; a mitochondrial targeted kinase. The rhomboid-dependent processing of these three proteins is required for their biological activities. Mutations in OPA cause the most prevalent early onset blindness mitochondrial disease called dominant optic atrophy; and both Pink1 and Omi have been linked to Parkinson's disease, underscoring the relevance of these discoveries. By undertaking a series of in vitro structure/function analyses, combined with in vivo assays in both yeast and flies, we hope to uncover the significance of the rhomboid cleavage event, and understand its relevance to mitochondrial function in human disease. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170364&lang=en |
| 170366 | The Effect of Outdoor Air Pollution on the Development and Prognosis of the Inflammatory Bowel Diseases | Kaplan Gilaad G | Kaplan, Gilaad G | University of Calgary | Alberta | Canada | 200809 | 300000.0 | CIHR New Investigator | Salary Programs | Social / Cultural / Environmental / Population Health | Population and Public Health | Air Pollution; Environmental Risk Factor; Inflammatory Bowel Diseases | Crohn's disease and ulcerative colitis are incurable diseases that affect a patient's gut. The causes of these diseases are not known. However, it most commonly occurs in industrial countries such as Canada that produce high levels of air pollution. Scientists have shown that air pollution can cause many problems such as worsening asthma, promoting heart attacks, and increasing the risk of cancer. Air pollution may cause sickness by promoting inflammation. The inflammation driven by air pollution is similar to the inflammation seen in patients who suffer from Crohn's disease and ulcerative colitis. Thus, it is possible that air pollution may cause inflammation that would result in Crohn's disease or ulcerative colitis. Because of this possibility we plan to study whether air pollution increases the risk of being diagnosed with Crohn's disease and/or ulcerative colitis. We plan to look at many people living in Alberta and follow them for several years to see who develops Crohn's disease and ulcerative colitis. We will then look to see how much air pollution occurs near their homes. We will also study individuals who are not diagnosed with Crohn's disease or ulcerative and see how much air pollution occurs near where they reside. Our hypothesis is that individuals who live in areas of higher air pollution will be more likely to be diagnosed with Crohn's disease or ulcerative colitis than individuals who live in regions of lower air pollution. Linking air pollution to the development of Crohn's disease and ulcerative colitis is important. If air pollution increases the risk of developing Crohn's disease or ulcerative colitis, then lowering air pollution may prevent these diseases in some patients. Discovering such a relationship would potentially give us the tools to prevent these debilitating conditions - a far more effective strategy then treating an incurable disease once it has occurred. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170366&lang=en |
| 170367 | Arterial thermoplasty in coronary artery bypass surgery | Janssen Luke J | Janssen, Luke J | McMaster University | Ontario | Canada | 200809 | 309483.0 | Operating Grant | Operating Grants | Biomedical | Circulatory and Respiratory Health | Coronary Artery By-Pass Surgery; Human Radial Artery; Myocardial Infarction; Thermal Injury; Vasospasm | A large percentage of Canadians suffer from coronary artery disease; coronary artery bypass graft (CABG) surgery is the treatment of choice for these people. Although the intent of performing CABG is to improve coronary bloodflow, a common complication is a sudden narrowing of the transplanted artery days/weeks after surgery (caused by contraction of a muscle around the artery). Current approaches aimed at preventing this problem -- ranging from drugs to physical interventions (e.g., stents; balloons; replacement) -- are too often inadequate and only used once the problem appears. A superior method for actual prevention of this post-surgical complication is desperately needed. A novel technique which is gaining a great deal of attention in the airway/asthma field may fill this gap. In asthma, a muscle which wraps around the airway contracts, making it hard to breath. Thermoplasty involves the direct application of heat energy to that muscle, provoking little or no immediate response in the patient; however, 12 weeks later, the muscle is gone, although other important cell types are still present and look completely normal. Most importantly, the asthma has been permanently treated. We intend to explore whether thermoplasty can be used to prevent the post-surgical constriction of the implanted arteries seen in CABG through the following three experiments: Specific aim #1: examine the sensitivity of pig arteries to direct application of heat energy. Specific aim #2: address the question of whether it is possible to adapt this approach to the treatment of the donor/graft arteries immediately before grafting into the recipient. We have attached abundant preliminary data which, together with our track record, attest to our ability to complete this project. This procedure is simple, cost-effective, easily adapted to the clinical setting, with the potential to greatly reduce or even eliminate the incidence and/or severity of post-operative complications. | 3 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170367&lang=en |
| 170379 | The Cedar Project: Exploring HIV and Hepatitis C Vulnerabilities among Young Aboriginal Drug Users in Three Canadian Cities | Spittal Patricia M | Spittal, Patricia M; Schechter, Martin T | University of British Columbia | British Columbia | Canada | 200809 | 1911647.0 | Operating Grant | Operating Grants | Social / Cultural / Environmental / Population Health | Infection and Immunity | Aboriginal Young People; Hepatitis C; Hiv; Multidisciplinary | During the past decade the number of Aboriginal people diagnosed with HIV in Canada has grown more than any other ethnicity. Although Aboriginal people comprise only 4% of BC's population, they represent more than 13% of all positive tests. Whereas the majority of infections are related to injection drug use, factors that explain elevated risk and transmission of HIV among Aboriginal young people who use illicit drugs are not well understood. The Cedar Project is an observational study addressing HIV and HCV related vulnerabilities of Aboriginal young people living in Vancouver, Kamloops and Prince George, BC. We have recently identified concerning rates of both HCV and HIV infection, transition to injection and crystal methamphetamine use. Having an established cohort designed and implemented with Aboriginal partners and investigators now allows us the opportunity to expand our work to include identification of resiliency and protective factors from the perspectives of Aboriginal young people and focus in particular on a case management intervention aimed at increasing utilization of HIV care among HIV positive Cedar participants. | 3 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170379&lang=en |
| 170384 | Immune responses and regulation in hepatitis C virus infection: Implications for immunotherapy | Agrawal Babita | Agrawal, Babita | University of Alberta | Alberta | Canada | 200809 | 602481.0 | Operating Grant | Operating Grants | Biomedical | Infection and Immunity | Cellular Immunology; Experimental Medicine; Hepatitis C Virus; Immune Responses; Immunotherapy; Liver Disease | Hepatitis C virus (HCV), leads to serious and permanent liver damage. Late stage disease due to HCV is the leading cause of liver transplantation in North America. The disease afflicts 175 million people worldwide, including 1-2 % of the North American population. There is no vaccine or immunotherapy currently available for the treatment of HCV infection. A combination of pegylated alpha-interferon and ribavirin is being used to treat HCV infected patients, but this treatment is not adequate, only works in a minority of patients, and has serious side effects associated with it. Therefore, there is a tremendous need to develop new therapeutic approaches and vaccines against this devastating virus. The focus of this project is to study immune responses against HCV and mechanisms how these immune responses are modified in HCV infection, so that novel immunotherapeutic and vaccine strategies can be designed and investigated. In our studies we have recently established mouse models of HCV infection. In the proposed project we will investigate the components of successful immune responses capable of clearing HCV, and study how immune responses are modulated in HCV infection, using cell culture and mouse models. This project will contribute significantly to the knowledge and understanding of immunity against chronic HCV infection and in the development of immunotherapy and vaccine candidates for the prevention and treatment of HCV infection worldwide. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170384&lang=en |
| 170393 | Novel tumour cell interactions in bone | Ghert Michelle A | Ghert, Michelle A | McMaster University | Ontario | Canada | 200809 | 315643.0 | Operating Grant | Operating Grants | Biomedical | Musculoskeletal Health and Arthritis | Ap-1; Bone; Cytokine; Giant Cell Tumour; Mmp-13; Runx2 | The skeleton is very important for daily activities such as walking and posture. It is hence important for quality of life for an individual. Cancers that primarily arise within the bone or that have spread to the bone can disrupt the architecture of the bone by altering the balance of bone formation and remodeling leading to overall bone destruction, pain and fracture. Giant Cell Tumour of bone is an aggressive bone tumour that typically affects young adults and requires extensive surgery for cure. Dr. Ghert's lab has done extensive research exploring the mechanisms involved in the destruction of bone by these tumours. The overall goal of Dr. Ghert's research is to develop effective targeted molecular treatment for cancers that affect bone in which bone formation and destruction are imbalanced. | 3 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170393&lang=en |
| 170396 | The Role of the Inflammasome in Renal Injury | Muruve Daniel A | Muruve, Daniel A | University of Calgary | Alberta | Canada | 200809 | 512080.0 | Operating Grant | Operating Grants | Biomedical | Infection and Immunity | Cytokines; Inflammation; Innate Immune System; Kidney Disease; Kidney Failure; Renal Tubular Epithelium | Kidney diseases are common in the general population. Many types of kidney disease are caused by toxins, poor circulation, diabetes and other insults. Invariably, these types of kidney injury result in either acute or chronic kidney failure which has a significant impact on patient health. When kidneys become injured, a significant component of inflammation is involved. It is known that inflammation that occurs during injury contributes to kidney failure resulting in a worse outcome. We have recently identified a new pathway of inflammation in the cell. We believe that this inflammatory pathway (called the inflammasome)is activated by the types of injury stated above such as poor circulation or toxins. The activation of the inflammasome contributes to the severity of the kidney injury and the ultimate outcome that is kidney failure. Research in this area may identify new pathways or understanding of kidney failure that can be targeted with drugs, that ultimately will help patients with kidney failure. | 4 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170396&lang=en |
| 170397 | Assembly and export of bacterial capsular polysaccharides | Whitfield Christopher | Whitfield, Christopher | University of Guelph | Ontario | Canada | 200809 | 748270.0 | Operating Grant | Operating Grants | Biomedical | Infection and Immunity | Capsular Polysaccharides; Cell Surfaces; Microbial Pathogens; Outer Membranes; Transport; Virulence Factors | The surfaces of bacteria are typically composed of a complex and dynamic array of carbohydrate-containing macromolecules. An extensive layer of polysaccharide known as the capsule covers the surfaces of many bacterial pathogens. Capsules have crucial roles in many interactions between bacteria and their environments, including interplay between invading bacteria and host cell defenses. Capsules are generally protective structures and treatments that eliminate capsules (or dramatically reduce their size) can render a bacterial pathogen susceptible to normal host defenses. Consequently, reactions involved in capsule synthesis represent potential targets for therapeutic intervention. Any attempts to develop capsule assembly as a therapeutic target requires a detailed understanding of the underlying processes and this is the goal of our work. We intend to characterize in detail the structure and function of two protein families involved in novel aspects of capsule assembly. The precise mechanisms of action of these proteins are unknown. However, representatives are widely distributed in bacteria, indicating that the results obtained will have broad impact. In addition, the complex processes underlying capsule assembly are of fundamental importance and our studies are expected to provide insight into other important cellular events in pathogenic bacteria. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170397&lang=en |
| 170399 | Application of User-Centered Participatory Design Research in the Development of an Online Intervention to Provide Social Support to Parents of Adolescents with Diabetes | Paterson Barbara L | Paterson, Barbara L | University of New Brunswick (Fredericton) | New Brunswick | Canada | 200809 | 148635.0 | Operating Grant | Operating Grants | Social / Cultural / Environmental / Population Health | Human Development, Child and Youth Health | Adolescence; Diabetes; Intervention; Parenting; Participatory Action Research; Social Support | Adolescence is a time when children with type 1 diabetes may resist parental involvement in their diabetes management but at the same time, they may neglect aspects of their self-management. Parents of adolescents with type 1 diabetes typically experience a number of stressors during this period, particularly in relation to making the transition between the main decision maker to assuming a minor role in regard to the child's diabetes management.The research is intended to design and develop an online social support intervention to assist parents in such a transition. It will draw on research approaches that entail working with parents of children with diabetes, service providers and web designers to develop a web-based intervention that meets the needs for social support of parents of adolescents with diabetes. | 2 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170399&lang=en |
| 170400 | Effects of prenatal ethanol exposure on hormonal regulation of hippocampal function. | Christie Brian R | Christie, Brian R | University of Victoria (British Columbia) | British Columbia | Canada | 200809 | 702545.0 | Operating Grant | Operating Grants | Biomedical | Gender and Health | Electrophysiology; Hippocampus; Hormones; Nmda Receptors; Sex; Synaptic Plasticity | Fetal alcohol spectrum disorders (FASD) result from the consumption of alcohol during pregnancy. This is the leading cause of preventable mental retardation in humans, but for a variety of reasons is not well understood. We do know that prenatal ethanol exposure (PNEE) kills some cells in the brain, and that this seems to lead to learning problems. Very little is known about how males and females are differentially affected by PNEE, though we do know that estrogen and testosterone differentially affect learning and memory processes. We will use the hippocampus, a part of the brain involved in learning and memory, as the main structure to study in this research. Using an animal model, we will determine how prenatal ethanol exposure alters hormonal control of the way neurons communicate in this structure. Our intent is to get to a stage where we can determine if hormone replacement therapy might be a suitable method for helping to ameliorate some of the cognitive deficits experienced by at least some of the individuals afflicted with FASD. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170400&lang=en |
| 170401 | The Multiple Cellular Functions of the Hsp90 Molecular Chaperone: The Role of Hsp90 and the Conserved R2TP Complex in Ribosomal RNA Processing | Houry Walid A | Houry, Walid A | University of Toronto | Ontario | Canada | 200809 | 677895.0 | Operating Grant | Operating Grants | Biomedical | Cancer Research | Cancer; Cochaperones; Helicases; Hsp90 Molecular Chaperone; Ribosomal Rna Processing; Snorna | Hsp90 is a ubiquitous molecular chaperone that is found in eubacteria and all branches of eukarya. It plays a central role in cellular signaling since it is essential for maintaining the activity of several signaling proteins including steroid hormone receptors and protein kinases. Hsp90 is typically overexpressed in cancer cells and is now the target of novel anti-cancer drugs, some of which are in clinical trials. Our research is currently concentrated on better understanding the functions of Hsp90 in the cell. We had previously identified a novel protein complex that interacts with Hsp90. Recently, we were able to show that the complex allows Hsp90 to modulate ribosome biogenesis. This is a very novel finding that has not been previously described and might have important clinical implications when using drugs to target Hsp90. The proposed project will further explore this novel activity of this essential chaperone. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170401&lang=en |
| 170402 | Exposure to environmental chemicals and psychomotor development: prospective birth study of neurotoxic effects using peripheral biomarkers (GESTE study) | Takser Larissa | Takser, Larissa | Université de Sherbrooke | Québec | Canada | 200809 | 300000.0 | CIHR New Investigator | Salary Programs | Social / Cultural / Environmental / Population Health | Human Development, Child and Youth Health | Biomarkers; Child Development; Environmental Exposures; Epidemiology; Reproduction; Toxicology | Neurodevelopmental disabilities affect 3-8% of babies born each year in North America, with known etiology for less than 25% of those disabilities. The potential for environmental contaminants to produce neurological, cognitive, or other behaviour deficits as a result of developmental exposure has received increasing attention. Most environmental chemicals exert their toxic effects in the foetus via circulating blood through the placenta. The foetus is more susceptible to toxic exposure than the adult due to its fragile and rapid developmental state and lack of adequate defence mechanisms. Based on existing knowledge of the toxicity of persistent environmental pollutants from experimental research, we hypothesize that environmental exposure to Mn, Cd, Pb, PCB, PBDE and Hg simultaneously during prenatal life associates with increased risk of poorer psychomotor performances in children from the general population. In order to ensure the safety of current levels of environmental exposures during prenatal life in pregnant women from the general population, we propose to conduct a birth prospective cohort using biomarkers of effect for a mixture of known persistent substances. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170402&lang=en |
| 170403 | Regulation of the gene transfer agent (GTA) of Rhodobacter capsulatus | Beatty John Thomas | Beatty, John Thomas | University of British Columbia | British Columbia | Canada | 200809 | 512507.0 | Operating Grant | Operating Grants | Biomedical | Genetics | Bacteria; Dna Virus; Gene Transfer Agent; Genetic Exchange; Molecular Biology | This work is to study how a bacterial cell controls the production of a virus-like particle (the gene transfer agent, or GTA) that has the sole function of transfering genes from a donor to a recipient cell. Our preliminary work indicates aspects of several changes in environmental conditions, such as the presence or absence of specific chemicals, that affect gene transfer. We wish to determine exactly how such chemicals, or 'signals', are sensed by cells and the biochemical pathways leading from signal sensation to the turn on/off of GTA genes. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170403&lang=en |
| 170406 | Intestinal Microbiota and the Gut-Brain Axis. | Collins Stephen M | Collins, Stephen M; Bercik, Premysl | McMaster University | Ontario | Canada | 200809 | 855635.0 | Operating Grant | Operating Grants | Biomedical | Infection and Immunity | Functional Gi Disorders; Gut Brain Axis; Microbiota | The gastrointestinal (GI) tract and the brain are intimately connected and behavioral factors are important in the expression of common GI diseases such as Irritable Bowel Syndrome (IBS). IBS is the most common GI disorder in our society but its cause is poorly understood and treatment is largely symptom-based; it does not cure. This condition is frequently accompanied by depression or anxiety and is considered by some to psychosomatic. Recent observations show that acute gastroenteritis can trigger IBS and that this may result in changes in the bacterial population that resides in the gut - known as flora. In this proposal, we will investigate whether changes in gut flora contribute to the expression of IBS using a mouse model. We have already shown that perturbing gut flora produces changes bowel function. As psychiatric conditions often accompany IBS, we will investigate whether the gut flora influence the brain and change behavior. The proposal uses molecular tools to identify gut bacteria and experiments are undertaken in a unique germ free laboratory to minimize contamination. If we succeed in showing that gut flora influence both gut function and behavior, then it will be possible to develop a single treatment strategy to treat all aspects of this condition. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170406&lang=en |
| 170407 | Abnormal Brain Development in Newborns with Congenital Heart Disease | Miller Steven P | Miller, Steven P | University of British Columbia | British Columbia | Canada | 200809 | 798370.0 | Operating Grant | Operating Grants | Clinical | Human Development, Child and Youth Health | Brain Development; Congenital Heart Disease; Developmental Outcome; Magnetic Resonance Imaging; Stroke; White Matter Injury | Heart birth defects are of the most common birth defects diagnosed in Canada, affecting 1 in 100 newborns each year. Impairments in motor and cognitive development are common in children born with heart birth defects and pose significant burdens on the child, family and society. These impairments are frequently attributed to brain injury secondary to the heart birth defect and may be acquired either before birth or in the weeks after birth. As yet, however, the reasons for brain injury in this population of newborns are poorly understood, limiting the development of effective therapies to prevent brain injury and to counsel parents regarding long term prognosis. Consequently, it is a high priority to improve our understanding of brain injury in newborns with heart birth defects. Our preliminary data suggest that brain development is impaired in newborns with heart birth defects. The overall hypothesis of this study is that delayed brain development results in abnormal motor and cognitive outcomes. We will quantify brain development and brain injury in term newborns with heart birth defects using advanced magnetic resonance (MR) techniques before birth (in utero), shortly after birth before heart surgery and again after heart surgery: MR imaging for brain injury, diffusion tensor imaging for brain connectivity and MR spectroscopic imaging for brain metabolism. We will then follow this group of newborns with heart birth defects through childhood to observe their motor and cognitive outcomes. A better understanding of brain injury that occurs in newborns with heart disease, and the ability to identify and quantify brain injury at a time when intervention is possible, is sorely needed to design and test new strategies for preventing or treating brain injury. The development of accurate measures of brain injury in newborns will also help parents and physicians better care for newborns with heart disease by providing important prognostic information. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170407&lang=en |
| 170414 | Genetic integrity of the haploid male germ cells | Boissonneault Guylain | Boissonneault, Guylain | Université de Sherbrooke | Québec | Canada | 200809 | 492712.0 | Operating Grant | Operating Grants | Biomedical | Genetics | Chromatin Remodeling; Dna Repair; Dna Strand Breaks; Genetic Integrity; Mutation; Spermatids | The nuclear structure of male germ cells changes drastically just before they become mature spermatozoa. This transition provides a much greater stability to the nucleus once completed. We have shown that this change in structure is associated with the formation of DNA breakage at both strands (double-stranded breaks) in every cell and that it occurs naturally. Because these precursor cells possess half the chromosome set of a normal (somatic) cells, any damage to DNA cannot rely on an intact copy for template repair making this transition a very sensitive one. Our objectives are to determine the distribution of DNA strand breaks within the genome, the repair mechanism involved, the genetic consequences of this transition as well as its sensitivity to drugs such as those used in chemotherapy. We may therefore unravel an as yet unsuspected but important source of genetic instability transmitted to the embryos with an evolutionary impact. | 4 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170414&lang=en |
| 170428 | Vitrification and transplantation of articular cartilage | Jomha Nadr M | Jomha, Nadr M | University of Alberta | Alberta | Canada | 200809 | 254422.0 | Operating Grant | Operating Grants | Biomedical | Musculoskeletal Health and Arthritis | Articular Cartilage; Mathematical Modeling; Metabolic Evaluation; Statistical Methodology; Transplantation; Vitrification | Injuries to and diseases of joint cartilage can lead to osteoarthritis (0A) affecting 4 million Canadians with 60% younger than 65 years of age. OA is the second leading cause of work disability in North America. This research seeks a treatment option (joint transplantation) for damaged joint cartilage thereby limiting development of OA. The best treatment option would be to transplant normal joint cartilage but timing required for tissue donation requires a preservation technique. Current preservation techniques for joint transplants rely on controlled ice formation but this kills the cells that maintain the joint cartilage matrix and physically damages the intricate structure of the cartilage matrix. We propose a method of preseving the integrity of joint cartilage by avoiding ice crystal formation (vitrification). Vitrification maintains cell viability and matrix structure allowing cartilage storage for later use in transplantation procedures for damaged joints, improving long-term clinical outcomes of currently performed Orthopaedic surgical techniques, and decreasing the risk of infectious disease transmission. The research proposed here will use a statistical approach to generate experimental data and compare this with mathematical modeling - a unique approach applied to preservation of joint cartilage. We will develop new vitrification solutions, learn about toxicity of various solutions and determine the ability of these agents to enter the matrix. The successful vitrification protocol will then be performed on a transplantation model in preparation for use in a joint transplantation program. This research can help prevent osteoarthritis from developing after joint injury, with the high likelihood of improving the quality of life locally and internationally. | 3 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170428&lang=en |
| 170430 | L'abolition du paiement des services de santé en Afrique de l'Ouest | Ridde Valéry | Ridde, Valéry | Centre hospitalier de l'Université de Montréal (CHUM) | Québec | Canada | 200809 | 300000.0 | CIHR New Investigator | Salary Programs | Health systems / services | Population and Public Health | Afrique; Financement; Politiques Publiques; Système De Santé; Équité | L'objet de notre programme de recherche réalisé en Afrique de l'Ouest vise comprendre si l'abolition du paiement direct des soins de santé est une stratégie efficace pour améliorer l'équité d'accès au système de santé. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170430&lang=en |
| 170461 | Improving Medication Use, Health Care and Quality of Life Through Innovative Health Outcomes Research | Cadarette Suzanne M | Cadarette, Suzanne M | University of Toronto | Ontario | Canada | 200809 | 300000.0 | CIHR New Investigator | Salary Programs | Health systems / services | Aging | Aging; Disease Prevention; Health Services Research; Osteoporosis; Pharmacoepidemiology | Administrative claims data are rich and provide information to study how drugs are used in the real-world, and thus also provide real-world drug safety and effectiveness data. We outline two pilot projects that will capitalize on administrative claims data from Ontario. First, valid estimates of the safety and effectiveness of therapeutics are required to help inform drug policy decision making. Unfortunately, results from claims-based observational studies are error-prone due to incomplete information. We will use innovative methods that supplement claims-based data with other data sources to examine the potential benefits of these analytic strategies in improving estimates of the safety and effectiveness of drugs. We will start by examining fracture outcomes among seniors. Second, we know that adherence to therapy for osteoporosis, hypertension and hypercholesterolemia is suboptimal. However, little information is available regarding the patterns of drug use or the implications of gaps in adherence to therapy for these conditions. We will study patterns of pharmacotherapy, predictors of large gaps in treatment and implications of gaps in adherence to therapy for these conditions, starting with osteoporosis. Results will help identify the burden of illness in the population related to suboptimal adherence, and may be used to help develop quality improvement interventions. Results from these pilot projects will help inform future innovative projects that will aim to reduce the burden of illness in the population due to adverse drug effects and failure to adhere to preventive pharmacotherapy. Results will be important to guide health policy, develop quality improvement interventions, reduce health care costs and ultimately reduce the burden of illness in the population due to adverse drug effects and suboptimal adherence to chronic pharmacotherapy. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170461&lang=en |
| 170462 | Molecular basis for Central Core Disease and RyR1-related myopathies | Maclennan David H | Maclennan, David H | University of Toronto | Ontario | Canada | 200809 | 925458.0 | Operating Grant | Operating Grants | Biomedical | Genetics | Animal Models; Biochemistry; Central Core Disease; Genetic Disease; Ryanodine Receptor; Skeletal Muscle | Muscle contraction is triggered by the release of calcium into muscle cells from a storage compartment inside the cells, referred to as the sarcoplasmic reticulum; relaxation is initiated by return of calcium to the storage compartment. Thus every bodily movement and every heartbeat is dependent on calcium fluxes. Calcium release channels are responsible for releasing calcium from the storage compartment to bring about muscle contraction. Two human diseases, malignant hyperthermia, a toxic response to anesthetics, and central core disease, causing muscle weakness, are caused by mutations in the skeletal muscle form of the calcium release channel. In recent work, Dr. MacLennan and his group have developed a mouse line in which the calcium release channel is mutated to an inactive form. When both copies of the mutant gene are present, the embryonic mouse displays a block in development; when only one copy is present, the mouse lives, but displays symptoms of muscle disease that are consistent with central core disease. Both of these mouse models of disease are interesting. The block in development is caused by the lack of calcium signals that direct proper development in mice, but these signals are not defined. Dr. Maclennan's group propose to identify these signals. The mouse with central core disease offers the opportunity for understanding how this and other muscle diseases develop and how intervention might ameliorate the effects of muscle diseases. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170462&lang=en |
| 170470 | Neural and Biomechanical Control of Turning in People with Stroke | Lam Tania | Lam, Tania | University of British Columbia | British Columbia | Canada | 200809 | 300000.0 | CIHR New Investigator | Salary Programs | Biomedical | Neurosciences, Mental Health and Addiction | Centre Of Pressure; Electromyography; Functional Mobility; Stroke; Treadmill Training; Turning | Although many people who had a stroke can get better and walk again, there are still problems with walking that limit their ability to fully take part in many daily activities. Up to now, stroke researchers have usually tested walking by asking people to walk forwards in a straight line. However, in everyday life people must constantly change their direction or turn while walking. The ability to turn is important to make sure that people are able to walk around safely and easily in their homes as well as outside in their communities. In addition, turning also poses a greater risk of falling compared with walking straight ahead. Despite these facts, there is very little research about turning and walking in people with stroke. Thus the overall objectives of this research are to understand how difficulties in walking affect turning in people with stroke. We will use recordings of muscle activity and leg movements during walking to analyze the differences in turning strategies in people with stroke compared with people who have not had a stroke. We will also study the extent to which different rehabilitation therapies for improving walking also help to improve turning ability in people who have had a stroke. The results from this research will help us develop better testing tools and training strategies for therapists to use as they work to help people who have had a stroke walk as well as possible. Ultimately, better walking ability will help promote healthier and more active lifestyles for people who have had a stroke. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170470&lang=en |
| 170474 | Combination pharmacotherapy for the management of pain (2008) | Gilron Ian | Gilron, Ian | Queen's University (Kingston, Ontario) | Ontario | Canada | 200809 | 416885.0 | Randomized Controlled Trials | Randomized Controlled Trials | Clinical | Neurosciences, Mental Health and Addiction | Analgesic Pharmacology; Anticonvulsants; Antidepressants; Chronic Pain; Clinical Pharmacology; Controlled Trials; Diabetic Neuropathy; Drug Combinations; Neuropathic Pain; Opioids; Pain; Pain Measurement; Randomized | Pain is a major public health problem affecting one-third of the population and costing $165 billion/year in North America alone. Individual pain-relievers provide incomplete relief and can often produce troubling side effects. It has been suggested that combining different kinds of pain-relievers may improve effectiveness and reduce side effects. Some drug combinations have been proven better than each of their components alone. However, this theory has been tested for very few specific drug combinations. Studies show that, on their own, the antidepressant drug, nortriptyline, and the opioid drug, morphine, partially relieve pain due to nerve disease. The main objective of this grant proposal is to determine whether using a combination of these two drugs relieves pain more effectively and/or causes less side effects than when using either drug alone. This objective will be met by conducting a clinical trial in diabetic patients with pain due to nerve disease. The research plan involves a double-blind, randomized crossover trial which compares chronic oral administration of a nortriptyline/morphine combination to single-agent nortriptyline or morphine in patients with painful diabetic neuropathy. During each of these treatment periods, drug dosage will be gradually increased to the highest possible dose, yet a dose which produces only minimal side effects. We expect to determine whether this combination is more beneficial than either drug alone. Future research using these methods will allow for the testing of other analgesic combinations for pain management. | 3 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170474&lang=en |
| 170476 | Peptide and Protein Structure in Membranes | Deber Charles M | Deber, Charles M | Hospital for Sick Children (Toronto) | Ontario | Canada | 200809 | 673230.0 | Operating Grant | Operating Grants | Biomedical | Genetics | Helix-Helix Interactions; Membrane Proteins; Protein Folding In Membranes; Protein Structure; Protein-Lipid Interactions; Transmembrane Helices | Embedded in the membranes of all living cells, membrane proteins are the molecular links between the inside and outside world. These proteins help preserve the biological structure of the cells; they act as receptors by participating in signaling (such as telling the cell when to 'grow'); and they act as transporters to regulate the flow of molecules into and out of the cell, including calcium or sodium ions, nutrients such as amino acids and sugars, as well as drugs and more complex molecules. Membrane proteins consist of long chains of amino acids; critical mutations even at a single point in the chain underlie the causes of many human diseases. These include several forms of cancer, diabetes, and cystic fibrosis. But it is very difficult to deduce the molecular mechanisms of a disease, and move toward drug design/therapy, without fundamental structural information about the overall protein. Our research involves studies of proteins and peptides, focusing on the protein segments that are physically integrated into the cell membranes. By using a variety of modern laboratory methods and instruments that can be applied to the determination of protein structure, we hope to discover how small variations in the amino acid sequence impact on the ability of the protein to function normally. This research should yield fundamental information as to how specific amino acids within membranes give rise to the correct protein function, and in the longer range will provide the rationale for ascribing a structural basis to the aberrant effects of disease-related mutations in membrane proteins. As we increase our understanding of these important molecules, we will be better positioned to develop therapies against diseases of these proteins. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170476&lang=en |
| 170477 | Facilitating physical activity behavior and health outcomes in breast cancer survivors receiving chemotherapy: A practical behavioral trial | Vallance Jeffrey K | Vallance, Jeffrey K | Athabasca University (Alberta) | Alberta | Canada | 200809 | 300000.0 | CIHR New Investigator | Salary Programs | Social / Cultural / Environmental / Population Health | Population and Public Health | Breast Cancer; Chemotherapy; Physical Activity; Practical Behavioral Trial; Quality Of Life; Step Pedometers | Few interventions can help breast cancer patients improve their physical strength, stamina, and overall well-being during chemotherapy. Literature is now suggesting that physical activity (PA) is a safe, feasible, and effective intervention for breast cancer patients receiving chemotherapy. Given the low PA rates among those receiving chemotherapy for breast cancer, developing practical ways to facilitate PA behavior during chemotherapy for breast cancer are necessary. Recently we evaluated and published an intervention to increase PA in breast cancer survivors (Activity Promotion Trial). Trial results indicated that a breast cancer PA guidebook and a step pedometer were effective strategies for increasing PA, and improving health-related quality of life and fatigue. The primary aim of this study is to determine if a PA guidebook for breast cancer survivors, a step pedometer, and supplementary step/pedometer resource are effective tools to help breast cancer patients receiving chemotherapy initiate and stay active during their treatments. This study will be a practical behavioral trial (PBT). Breast cancer patients receiving the intervention will be compared to a group receiving only a generic 2- page PA leaflet. Our primary interest is in average physical activity minutes per week, which we will measure before their first and after their last chemotherapy treatment. On various rating scales, patients will also be asked about their current PA, perceived quality of life, fatigue, depression, anxiety, and self-esteem. This trial explores practical and evidence-based strategies in which breast cancer patients receiving chemotherapy can learn about and engage in PA during chemotherapy. This trial will also give Southern Alberta breast cancer patients an opportunity to participate in evidence-based programs designed to facilitate their health, breast cancer recovery, and disease-free survival. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170477&lang=en |
| 170478 | Facilitating physical activity behavior and health outcomes in breast cancer survivors receiving chemotherapy: A practical behavioral trial | Vallance Jeffrey K | Vallance, Jeffrey K | Athabasca University (Alberta) | Alberta | Canada | 200809 | 187963.0 | Operating Grant | Operating Grants | Social / Cultural / Environmental / Population Health | Population and Public Health | Breast Cancer; Chemotherapy; Physical Activity; Practical Behavioral Trial; Quality Of Life; Step Pedometers | Few interventions can help breast cancer patients improve their physical strength, stamina, and overall well-being during chemotherapy. Literature is now suggesting that physical activity (PA) is a safe, feasible, and effective intervention for breast cancer patients receiving chemotherapy. Given the low PA rates among those receiving chemotherapy for breast cancer, developing practical ways to facilitate PA behavior during chemotherapy for breast cancer are necessary. Recently we evaluated and published an intervention to increase PA in breast cancer survivors (Activity Promotion Trial). Trial results indicated that a breast cancer PA guidebook and a step pedometer were effective strategies for increasing PA, and improving health-related quality of life and fatigue. The primary aim of this study is to determine if a PA guidebook for breast cancer survivors, a step pedometer, and supplementary step/pedometer resource are effective tools to help breast cancer patients receiving chemotherapy initiate and stay active during and after their treatments. This study will be a practical behavioral trial (PBT). Breast cancer survivors receiving the intervention will be compared to a group receiving only a generic 2- page PA leaflet. Our primary interest is in average physical activity minutes per week, which we will measure before their first and after their last chemotherapy treatment. On various rating scales, survivors will also be asked about their current PA, perceived quality of life, fatigue, depression, anxiety, and self-esteem. This trial explores practical and evidence-based strategies in which breast cancer patients receiving chemotherapy can learn about and engage in PA during chemotherapy. This trial will also give Southern Alberta breast cancer patients an opportunity to participate in evidence-based programs designed to facilitate their health, breast | 3 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170478&lang=en |
| 170480 | Cytokines and stressors influence depression: sensitization and cross sensitization | Anisman Hymie | Anisman, Hymie | Carleton University (Ottawa) | Ontario | Canada | 200809 | 823380.0 | Operating Grant | Operating Grants | Biomedical | Neurosciences, Mental Health and Addiction | Crh; Cytokine; Depression; Gaba; Serotonin | Stressful events are known to promote major depressive disorder, and the occurrence of such an outcome is more pronounced among individuals that had previously experienced major life stressors. Indeed, it seems that with each stressor experience, and with each episode of depression, the interval between depressive episodes becomes shorter, the depression more severe and long lasting, and the stressor severity necessary to promote the episode is less intense. Activation of the inflammatory immune system, and particularly activation of immune signaling molecules (termed cytokines), engenders neuroendocrine and brain chemical changes like those elicited by stressors, and might thus come to elicit depression. The intent of the proposed experiments is to determine the contribution two particular cytokines, namely interleukin-1 and interleukin-6, in promoting brain chemical changes thought to underlie depression. Of particular interest is to establish whether initial immune activation exacerbates neurochemical and behavioral responses ordinarily elicited by later immune and stress challenges. Moreover, we will establish whether and how stressful events influence the response to later immune challenges and determine the processes by which sensitization and cross sensitization effects occur. The recurrence of depression is a major obstacle in the treatment of this disorder, and the proposed studies may help to identify factors that contribute to illness recurrence. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170480&lang=en |
| 170482 | Characterization of B cell tolerance and functional abnormalities in human lupus | Wither Joan E | Wither, Joan E | University Health Network (Toronto) | Ontario | Canada | 200809 | 363714.0 | Operating Grant | Operating Grants | Biomedical | Infection and Immunity | Autoimmunity; B Cells; Lupus; Tolerance | The immune system plays an important role in discriminating between proteins that are foreign to the body, such as those in the bacteria and viruses that cause infections, and proteins that are normal parts of the body, such as those found in organs like the kidney and the brain. Foreign proteins are attacked preventing overwhelming infection while self-proteins are normally left unharmed. We believe that Systemic Lupus Erythematosus (SLE) results from defects in the immune system that lead to abnormal activation of cells that react to self-proteins. In the immune system two classes of cells, T and B cells, act in concert to mount an immune response. In many strains of mice that develop a lupus-like illness, B cell functional abnormalities play a central role in the pathogenesis of disease, yet the function of B cells in human lupus has not been well explored. Nevertheless, we, and others have shown that the B cells of humans with lupus are abnormally activated suggesting that they too have altered function. Here we seek to identify the functional abnormalities in the B cells of lupus patients and to determine whether they lead to altered responses to self-proteins. Identification of such abnormalities could ultimately lead to characterization of the underlying biochemical and genetic defects that produce SLE and more effective therapies for this condition. | 3 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170482&lang=en |
| 170495 | The Role of Endocytic Proteins at Bacteria-Induced Pedestals | Guttman Julian A | Guttman, Julian A | Simon Fraser University (Burnaby, B.C.) | British Columbia | Canada | 200809 | 300000.0 | CIHR New Investigator | Salary Programs | Biomedical | Infection and Immunity | Animal Models; Attaching And Effacing Pathogens; Clathrin-Based Endocytosis; Host-Pathogen Interactions; Protein Localization; Rna Interference | Pathogenic E.coli infections are a serious global health concern. During their disease processes, these organisms remain outside of host cells and inject a multitude of pathogenic proteins to commandeer normal cellular functions. A characteristic feature of these diseases involves the generation of host cell protrusions beneath the attached bacteria that results in these microbes rising off the natural surface of the cell onto E.coli generated structures called, pedestals. Surprisingly, I recently found that clathrin, a protein known to internalize particles and other bacteria into cells, is an essential component of pedestals and is required for their generation, thus providing a previously unknown function of this protein. In order to understand the mechanisms involved in the non-internalization functions of clathrin, I will examine the subversion strategies that pathogenic E.coli use to avoid clathrin-based internalization in order to remain extracellular. In addition to understanding the methods used by these bacteria to generate disease, this work will also provide insight into the general mechanisms of controlling particle internalization thus allowing for the design of therapeutics. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170495&lang=en |
| 170502 | Night waking reduction in Canadian infants: A randomized clinical trial of a parent-based cognitive and behavioural intervention in community health units | Hall Wendy A | Hall, Wendy A | University of British Columbia | British Columbia | Canada | 200809 | 301060.0 | Randomized Controlled Trials | Randomized Controlled Trials | Social / Cultural / Environmental / Population Health | Population and Public Health | Behavioural Sleep Problems; Cognitive And Behavioural Intervention; Community Health Nurses; Group Intervention; Infants; Parents; Randomized Controlled Trial | Infant behavioural sleep problems affect up to 50% of infants and contribute to adverse effects for infant development and parents' health. A significant proportion of infants do not grow out of sleep problems. Health care professionals often fail to recognize and treat infant behavioural sleep problems. Parents are exposed to conflicting advice which is frustrating and can undermine their parenting confidence. Extensive research has linked parents' cognitions and behaviours to the development and perpetuation of infant sleep problems. One-on-one approaches to treating behavioural sleep problems have empirical support; however, they often last for several weeks, are costly, and are not widely available to parents. A simple, inexpensive cognitive-behavioural intervention for groups of parents is available to be offered by public health nurses to improve infant sleep problems. Such interventions have not been offered in Canada. An effective, widely available sleep intervention can improve infants' and parents' well being. | 2 yrs 6 mths | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170502&lang=en |
| 170503 | Adaptive servo ventilation for therapy of sleep apnea in heart failure | Bradley Douglas T | Bradley, Douglas T | Toronto Rehabilitation Institute-UHN | Ontario | Canada | 200809 | 1583255.0 | CIHR/SME Collaborative Research Program - Randomized Controlled Trials | Randomized Controlled Trials | Clinical | Circulatory and Respiratory Health | Adaptive Servo Ventilation; Central Sleep Apnea; Heart Failure; Obstructive Sleep Apnea; Randomized Trial | Heart failure (HF) affects 2% Canadians and is now the second leading cause of death. It is therefore important to identify potentially treatable factors that could improve the outcome of this disease. Obstructive and central sleep apnea (OSA and CSA, respectively) may be 2 such factors. They occur in approximately 50% of patients with heart failure (HF), where they increase the risk of premature death. Previous studies have shown that treating these 2 breathing disorders with continuous positive airway pressure (CPAP) improves heart function. However, owing to the small number of patients studied, and that CPAP is ineffective in alleviating CSA in many patients, these studies did not demonstrate that treating OSA or CSA reduces morbidity and mortality. Nevertheless, among HF patients with CSA, when CPAP did eliminate CSA, survival improved. Thus, there seems to be potential for treating OSA and CSA to improve survival in HF patients. Adaptive servo ventilation (ASV) is a new device that is equally effective in alleviating OSA, but more effective in alleviating CSA than CPAP. We therefore believe that this device has a greater chance to improve survival than CPAP. Accordingly, we will test the effects of ASV on death and hospitalization rates in 860 HF patients with OSA or CSA in 25 centres in Canada and 6 other countries. Positive results would fundamentally alter the way HF is investigated and treated. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170503&lang=en |
| 170510 | Dose-response effects of exercise on abdominal obesity and risk factors for cardiovascular disease in women and men | Ross Robert M | Ross, Robert M | Queen's University (Kingston, Ontario) | Ontario | Canada | 200809 | 1803489.0 | Randomized Controlled Trials | Randomized Controlled Trials | Clinical | Nutrition, Metabolism and Diabetes | Cardiovascular Disease; Exericise Intensity And Volume; Glucose Tolerance; Obesity; Visceral Fat; Waist Circumference | The worldwide prevalence of abdominal obesity and associated disease and death among adults is increasing at alarming rates and requires immediate attention. Physical inactivity is a major determinant of obesity. Approximately 60% of adult Canadians are inactive; a factor that contributes to the rising prevalence of overweight that now exceeds 60%. The specific exercise strategy required to achieve optimal benefit for reduction of obesity and associated disease continues to be the source of considerable uncertainty and debate. At present health professionals know little about the specific type, amount and intensity of exercise that provides optimal or even measurable health benefit. This represents a major gap in knowledge with direct practical and clinical implications. In response, we propose to perform a rigorously controlled randomized trial inherent to which are four key characteristics. First, the use of waist circumference as opposed to BMI as the principal obesity-related outcome variable. Second, the prescription of exercise without a reduction in caloric intake, thereby isolating the effect of exercise on the primary outcomes. Third, precise control for exercise dose (how much) and intensity (how hard) with continual adjustment for improvement in fitness throughout the study. Fourth, recruitment of abdominally obese men and women at elevated health risk. These key features highlight our response to the limitations of prior investigations and will help resolve uncertainties regarding the utility of exercise as a means of reducing abdominal obesity and related health risk which impair the development of strategies for the promotion of obesity reduction in public health, clinical and community settings. This is timely as the number of Canadians at increased obesity-related health risk is high and increasing and hence, the development of efficacious lifestyle-based strategies designed to reduce obesity and related health risk is of paramount importance. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170510&lang=en |
| 170515 | A Randomized Controlled Evaluation of "Extended Specialized Early Intervention Service" vs "Regular care" for Management of Early Psychosis over the Five year Critical Period | Malla Ashok K | Malla, Ashok K; Joober, Ridha | CIUSSS de l'Ouest-de-l'Ile-de-Montréal-Douglas Hospital | Québec | Canada | 200809 | 2367886.0 | Randomized Controlled Trials | Randomized Controlled Trials | Clinical | Neurosciences, Mental Health and Addiction | Controlled Trial; First Episode; Multicenter; Psychosis; Routine Care; Specialized Early Intervention | The generally poor long term outcome in schizophrenia and related psychotic disorders is established relatively early in the first five "critical" years after onset. Specialized Early Intervention (SEI) service is a relatively new concept in mental health and is designed to improve outcome through provision of a comprehensive package of phase specific interventions provided early in the course of these disorders. While the results of this early intervention approach to treatment of a first episode of psychosis (FEP) for outcome in the first two years are encouraging, these benefits are not sustained over the subsequent three years if the person is transferred back to routine mental health care. We, therefore, propose to conduct a randomized controlled study of FEP patients who have already received two years of specialized treatment by comparing the effectiveness of extending the SEI service for another three years with patients who after the first two years of SEI are transferred to routine care which is what they would expect to receive under current circumstances. We will also assess the cost-effectiveness of this approach. This study would provide us answers to the question whether a specialized early intervention approach should extend to the entire risk period of the first five years. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170515&lang=en |
| 170517 | Arginine methylase PRMT1 and PRMT6 in cancer and genomic instability. | Richard Stéphane | Richard, Stéphane | CIUSSS de Centre-Ouest-de-l'Ile-de-Montréal-Jewish General | Québec | Canada | 200809 | 877100.0 | Operating Grant | Operating Grants | Biomedical | Cancer Research | Arginine Methylation; Cancer; Cell Cycle Control; Conditional Knockout Mice; Dna Damage Response; Genomic Instability | The detection and repair of DNA damage are vital for cell viability. DNA repair defects lead to DNA translocations, deletions/ mutations, chromosome breakage leading to 'genomic instability' and cancer. Several human genetic disorders are associated with failure to repair DNA including the rare human recessive diseases include ataxia telangiectasia (AT), Nijmegen breakage syndrome (NBS), ataxia telangiectasia like disease (ATLD), Fanconi anemia, and the Bloom, Werner, and Rothmund-Thompson syndromes. We discovered that a protein modification called 'arginine methylation' is necessary to repair damaged DNA. It is known that when we expose ourselves to UV light, for example, we introduce DNA damage in our skin cells and this increases the chances of us developing cancer. We showed previously that cells without the enzymes that deposit arginine methylation accumulate DNA damage and are prone to cancer development. We were the first to show this unique role of arginine methylation and herein we propose to continue these studies. We intend to use a basic science approach to study the role of arginine methylation in the process of repairing DNA damage. Genetic (using mice models) and biochemical approaches will be utilized to define the molecular targets of arginine methylation. What are the targets of the enzymes that deposit the arginine methylation marks required for this role in DNA repair? Our work predicts that if we can inactivate the enzymes that deposit arginine methylation (methylases) this will sensitize cells to radio- and chemotherapeutic agents such that lower doses may be required in the clinic for treatment. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170517&lang=en |
| 170520 | Regulation of PAF receptor function | Rola-Pleszczynski Marek | Rola-Pleszczynski, Marek; Stankova, Jana | Université de Sherbrooke | Québec | Canada | 200809 | 719447.0 | Operating Grant | Operating Grants | Biomedical | Circulatory and Respiratory Health | Cell Signaling; G-Protein-Coupled Receptor; Lipid Mediator | Le PAF est une petite molecule bioactive qui attire et active les leucocytes. Il joue un role important dans plusieures maladies inflammatoires et allergiques, telles l'asthme et le choc septique. Son action, au niveau cellulaire, passe par une structure proteique appelee recepteur (ou PAFR) qui transmet son signal vers l'interieur de la cellule et qui l'active. Nos travaux recents nous ont permis de determiner que certaines substances peuvent reduire la transmission de certains signaux par le PAFR. Enfin, certains elements de la structure meme du PAFR semblent jouer un role essentiel dans la transmission du message activateur du PAF a la cellule et ceux-ci peuvent etre bloques par des fragments synthetiques du PAFR. Dans le present projet, nous planifions determiner comment le PAFR est capable d'activer le leucocyte et comment cette reponse est attenuee par une retroaction negative. Ces etudes presentent le grand interet de pouvoir definir des elements et des etapes de l'activation cellulaire par le PAF qui pourront eventuellement etre amenables a un controle pharmacologique dans le but de limiter ou prevenir les effets inflammatoires indesirables du PAF. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170520&lang=en |
| 170521 | Investigating the mechanisms of Nod-like receptor-induced cytokine release and cell death in macrophages | Kim Sung O | Kim, Sung O | Western University (Ontario) | Ontario | Canada | 200809 | 640450.0 | Operating Grant | Operating Grants | Biomedical | Infection and Immunity | Caspase; Cell Death; Inflammasome; Lysosome; Macrophage; Mitochondria | Macrophages are key immune cells for detecting and eliminating microbial pathogens. Many pathogens induce macrophage death as a virulence tactic to survive and disseminate within the host. Recent studies have identified a family of intracellular receptors known as the nucleotide-binding domain and leucine-rich repeats(NLRs) which recognize intracellular microbial components. Activation of these receptors in macrophages induces rapid release of key inflammatory cytokines and macrophage cell death. Production of cytokines induces inflammation and is important for limiting microbial infections. However, rapid cell death can cause the spillage of unnecessary inflammatory mediators, resulting in overwhelming local inflammation and tissue damages, and defects in immune system by depleting macrophages. However, detailed mechanisms regarding the process of cytokine release and cell death remains to be investigated. This study is to investigate detailed signaling and molecular mechanisms of cytokine release and cell death, and examine the contribution of macrophage death during bacterial infections. This study will provide valuable and fundamental information on interactions between microbes and the host cells, and provide information on designing novel therapeutic tools for treating various bacterial and viral infections. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170521&lang=en |
| 170522 | HMG-CoA reductase in Alzheimer's Disease: Identification of a novel protective variant and unique polymorphisms that modulate Alzheimer pathophysiology. | Poirier Judes | Poirier, Judes | CIUSSS de l'Ouest-de-l'Ile-de-Montréal-Douglas Hospital | Québec | Canada | 200809 | 671999.0 | Operating Grant | Operating Grants | Biomedical | Aging | Alzheimer'S Disease; Cell Biology; Cholesterol; Genetics; Lipid; Molecular Biology | This renewal proposal seeks to further characterize the molecular mechanisms involved in the loss of specific brain cells in common Alzheimer's disease (AD). Over the recent years, our laboratory has documented a complex mechanism that controls the synthesis, recycling and transport of the cholesterol in response to neuronal cell death and local reinnervation in the adult brain. More recently, our team has identified novel genetic anomalies (called mutations) in proteins involved in the production cholesterol in the brain that selectively destroy specific groups of brain cells in AD. This research revealed that a protein known as 3-hydroxy-3-Methylglutaryl-Coenzyme A reductase (HMG CoA reductase) which normally controls the production of cholesterol in the brain is abnormally behaving in the brain of Alzheimer subjects and accelerates the onset of the disease in some cases. Recently, we found a novel and very specific genetic variation in the same HMG CoA reductase gene that confers natural protection against common Alzheimer's disease in humans born with this peculiar genetic trait. More importantly, it provide us with important insights as to how we could to slow down disease progression with specific medications and may be, delay the onset of the disease in people who are genetically "at risk" of developing the disease. Accordingly, the research program submitted here for funding proposes to extend our recent findings in order to examine the fine structure of this gene, its expression level and function in the brain, to eventually determine the exact mechanisms by which of these genetic anomalies (DNA variants) in the HMG-CoA reductase gene play a role in triggering and/or protecting humans against the common form of Alzheimer's disease. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170522&lang=en |
| 170523 | From oncogenes to genomic medicine: a social and historical analysis of translational cancer research | Cambrosio Alberto | Cambrosio, Alberto; Keating, Peter | McGill University | Québec | Canada | 200809 | 283013.0 | Operating Grant | Operating Grants | Social / Cultural / Environmental / Population Health | Health Services and Policy Research | Cancer; Genomics; History; Oncogenes; Sociology; Translational Research | Promoters of genomic medicine, that is to say, medicine informed by the results of the recent mapping of the human genome, promise a revolution in all areas of clinical practice ranging from diagnosis to prognosis and therapeutics. From personalized medicine to genomic markers of disease and responses to therapy, the results of the application of such technologies as genome-wide mapping are expected to be wide-ranging, substantive and rapid. The purpose of the present proposal is to investigate the introduction of genomic techniques and concepts in the field of cancer medicine from two points of view: the historical and the sociological. The historical part of our study will concentrate on an analysis of the public, academic and commercial programs designed to capitalize on the therapeutic insights offered by the new molecular genetics of cancer inaugurated in the early 1980s with the discovery of the first human oncogenes. The sociological analysis will continue the study into the post-genomic era and will target the rearrangement of the relations between the laboratory and the clinic (often referred to as translational research) that results in the emergence of new collective modes of practice and interaction in the biomedical sciences. | 4 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170523&lang=en |
| 170526 | Metabolic Regulation of Toll-like Receptor Agonist Therapy in Leukemia | Spaner David E | Spaner, David E | Sunnybrook Research Institute (Toronto, Ontario) | Ontario | Canada | 200809 | 380709.0 | Operating Grant | Operating Grants | Biomedical | Cancer Research | Apoptosis; Cancer; Cytokines; Flow Cytometry; Glucose; Mitochondria | Chemotherapy does not cure most cancers. However, the results with chemotherapy may be improved with treatments that increase the ability of the immune system to kill cancer cells (or immunotherapy). We have found that a new agent (called S28690), which activates a receptor on immune cells, called Toll-like receptor 7 (or TLR7), makes tumor cells more susceptible to both chemotherapy in the test tube but is not as effective in patients. The proposed research will determine how to make S28690 more effective in patients with Chronic Lymphocytic Leukemia, which is a tumor of the blood system. If these studies are successful,a new treatment for leukemia, and possibly other cancers, will become available. | 3 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170526&lang=en |
| 170530 | Targetting and Regulation of Ion Transporters | Grinstein Sergio | Grinstein, Sergio | Hospital for Sick Children (Toronto) | Ontario | Canada | 200809 | 939768.0 | Operating Grant | Operating Grants | Biomedical | Circulatory and Respiratory Health | Acid-Base Regulation; Fluorescence Imaging; Ion Transport; Na/H Exchange; Ph Regulation | The acid-base balance of organisms, including humans, must be carefully regulated. Both the pH (a measure of the concentration of acid) of cells and of the fluids that bathe them, including blood, are continuously challenged, yet maintained within very narrow boundaries. This exquisite regulation is attributable to a family of molecules that transport acid or base across the cell membranes. Among the most active and important transporters are the sodium/proton exchangers, a family of 9 different types of molecules widely distributed throughout the body. Several of these have been linked to various types of neurological, vascular and renal disease. The work described in this proposal has three separate aims: 1) Understanding how one of the prototypical sodium/proton exchangers, NHE3, interacts with and is regulated by the charge of the cell membrane; 2) To use yeast as a vehicle to express and study the NHE6-9 exchangers, which have proven otherwise intractable and 3) To devise and implement a method to study the electrical potential that develops across the membrane of endosomes, organelles that carry cargo into the cells. This fundamental knowledge will contribute to our understanding and eventual treatment of disease. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170530&lang=en |
| 170533 | Expanding the utility of hematopoietic stem cell products for vascular repair | Allan David S | Allan, David S | Ottawa Hospital Research Institute | Ontario | Canada | 200809 | 300000.0 | CIHR New Investigator | Salary Programs | Clinical | Circulatory and Respiratory Health | Blood And Marrow Transplantation; Bone Marrow; Nod/Scid Mouse Assay; Regenerative Medicine; Umbilical Cord Blood; Vascular Progenitors | This research addresses the use of blood stem cell products to restore blood flow into damaged tissues. Blood stem cell products used for transplantation include bone marrow, peripheral blood stem cells, and umbilical cord blood. These blood products can also be transfused to assist in the repair of organ damage caused by disruptions in blood flow, termed ischemic injury. New blood vessel formation is a critical first step in the repair of ischemic tissue damage. The precise cells and proteins that are most critical for vascular repair are not fully understood and we plan to characterize specific cell subsets that are most enriched for the ability restore healthy vasculature into damaged tissues. Further, in this research, proteins will be identified that are central to the vascular repair process. An immunosuppressed mouse model will be used which accepts human cells. Specialized cells will be isolated and tested for their ability to form new blood vessels in the mice. This will allow for quantification and comparison of vascular function between specific cell populations from human umbilical cord blood, bone marrow, and peripheral blood stem cell products. Using an animal model for our experiments provides biological data that will be important for developing strategies that could be used in humans. Identifying proteins that are present in blood stem cell products with increased blood-forming function will allow us to characterize important signals associated with successful vascular regeneration. Biomarkers or signals will be critical for optimizing cellular regenerative therapy. Our work will provide a platform for developing cell therapy for the treatment of heart attacks, strokes, some types of kidney failure and some cases of trauma or accidents. The potential for widespread application of regenerative vascular therapy underscores the clinical importance of this emerging area and the possibility of a profound impact on the health of Canadians | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170533&lang=en |
| 170534 | Brain mechanisms underlying the typical and atypical development of the mathematical brain | Ansari Daniel | Ansari, Daniel | Western University (Ontario) | Ontario | Canada | 200809 | 667110.0 | Operating Grant | Operating Grants | Not applicable / Specified | Neurosciences, Mental Health and Addiction | Developmental Cognitive Neuroscience; Developmental Dyscalculia; Functional Magnetic Resonance Imaging; Individual Differences; Intraparietal Sulcus; Numerical Cognition | Most of us deal with numbers efficiently, oftentimes without being aware of it. A good example is reading a newspaper article. In the process of doing so, you will encounter several pieces of numerical information, such as dates, the number of people involved in a given incident, a statistic to illustrate a particular point etc. While the majority of us will process and integrate this numerical information seamlessly, there exist a substantial percentage of individuals whose intelligence is in the normal range, but who struggle with even the most basic numerical and mathematical information and problems. These individuals are said to have Developmental Dyscalculia. This specific difficulty with numbers and math presents a significant impairment to educational, social and professional development. In stark contrast to the wide body of work on the causes and symptoms of Developmental Dyslexia (specific difficulty with reading), there currently exists only a few research studies which have investigated the behavioural and brain-level characteristics of Developmental Dyscalculia. The aim of my program of research is to provide insights into the neural and behavioural roots of this disorder, in an effort to inform the design, implementation and evaluation of research-based intervention tools. More specifically, through a series of three research projects, my research lab will use brain imaging techniques to investigate a.) how individual differences in mathematical competence among typically developing children relate to brain activation and structure b.) how the brain activation and structure of children with Developmental Dyscalculia differ from children with normal mathematical skills, and c.) to understand the relationship between developmental difficulties in reading and mathematics, that is, how Dyscalculia and Dyslexia differ in terms of brain structure and function and how these groups differ from children who have both Developmental Dyscalculia and Dyslexia | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170534&lang=en |
| 170561 | Mechanisms of mast cell-dependent tumor growth inhibition. | Marshall Jean S | Marshall, Jean S | Dalhousie University (Nova Scotia) | Nova Scotia | Canada | 200809 | 781265.0 | Operating Grant | Operating Grants | Biomedical | Cancer Research | Cancer; Innate Immunity; Mast Cells | A number of bacterial and viral products have been shown to reduce tumor growth in models of cancer and in clincal trials, however we have a poor understadning of how these work. Mast cells are immune cells often associated with allergic disease. They are increased in numbers around solid tumors and could regulate local anti-tumor immunity. Mast cells have been well studied in a variety of disease models and they are known to be able to initiate the development of effective immunity against a number of pathogens. Preliminary studies in Dr. Marshalls laboratory have recently shown that when activated with certain bacterial products, mast cells can reduce the rate of tumor growth in models of melanoma and lung cancer. Mast cells appear not to kill tumor cells directly but to recruit other cell types and modify the bodys response to tumors in a way that prevents tumor growth. There are three major objectives to the current study. The first will examine how mast cells might modify the immune response to tumors by recruiting immune cells to tumor sites. The second will examine how mast cells might prevent tumors developing their own blood supply or enhance their susceptibility to immune cell killing through production of a protein called interferon-gamma. A third series of studies will examine how mast cell production of a protein known as interleukin-6 can increase anti-tumor immunity. These studies will allow us to assess the potential of using selective mast cell activation in cancer therapy and to better understand the mechanisms whereby certain bacterial products prevent tumor growth | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170561&lang=en |
| 170562 | Regulatory polymorphisms in apoptosis genes and susceptibility to childhood leukemia | Sinnett Daniel | Sinnett, Daniel | Centre hospitalier universitaire Sainte-Justine (Montréal, Québec) | Québec | Canada | 200809 | 410877.0 | Operating Grant | Operating Grants | Biomedical | Genetics | Apoptosis; Biostatistics; Cancer Genetics; Childhood Leukemia; Electromobility Shift Assays; Gene Expression | Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, but little is known about the cause(s) of this disease. We have shown that the origin of childhood ALL could be explained by the interaction between genetic factors and environmental exposures. Here we propose that the susceptibility (or resistance) to childhood ALL is modified by functional variations in the sequences regulating the expression (promoter) of genes coding for programmed cell death (apoptosis). This hypothesis will be tested by performing genetic studies in ALL children (cases) and healthy individuals (controls). The expected results will provide new knowledge on how genes and the mechanisms of gene regulation lead to disease susceptibility or resistance. In the long term, these findings will allow the development of ALL prevention programs for the population. | 3 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170562&lang=en |
| 170570 | FLUID LAVAGE OF OPEN WOUNDS (F.L.O.W.): A Multi-center, Blinded, Factorial Trial Comparing Alternative Irrigating Solutions and Pressures in Patients with Open Fractures | Bhandari Mohit | Bhandari, Mohit; Guyatt, Gordon H | McMaster University | Ontario | Canada | 200809 | 1756616.0 | Randomized Controlled Trials | Randomized Controlled Trials | Clinical | Population and Public Health | Factorial Design; Fluid Irrigation; Infections; Multicenters; Open Fractures; Randomized Trial; Reoperations | Traffic accidents ranked among the top 10 causes of global disability in 1990. By 2020, disability from traffic accidents is estimated to rank in the top 3 of all cause disability from disease - second only to ischemic heart disease and depression. The most serious injuries are those fractures that break through the skin. These so called open, or compound, fractures have serious consequences for patients including infections, wound healing problems and failure of fracture healing-many of which necessitate a secondary intervention, or re-operation. For this reason, open fractures are designated as surgical emergencies and require urgent treatment. In North America, an estimated 250,000 open fractures occur annually. The single most important step in the initial management of these complex injuries is a thorough wound irrigation to remove any contaminants. We aim to evaluate whether the type of irrigation solution (soap vs. saline) or irrigation pressure (low vs. high; gravity flow vs. high) will decrease the risk for re-operation among adult patients with open fracture wounds. We secondarily aim to determine the effect of irrigating solution and irrigation pressure on patient function and quality of life. We hypothesize that soap solution may be more effective for reducing risk of infection compared to saline, and that low-pressure and gravity-flow-pressure irrigation will result in fewer re-operations than high-pressure. This trial has the potential for global impact change in resolving the current controversy with irrigation solutions and pressures for care of open fractures. | 4 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170570&lang=en |
| 170575 | Efficacy of a physical therapy intervention for the early treatment of acute ankle sprains identified in the emergency department: a randomized controlled trial | Brison Robert J | Brison, Robert J; Brouwer, Brenda J | Queen's University (Kingston, Ontario) | Ontario | Canada | 200809 | 703111.0 | Randomized Controlled Trials | Randomized Controlled Trials | Clinical | Musculoskeletal Health and Arthritis | Ankle Sprain; Epidemiology; Functional Recovery; Physiotherapy; Randomized Control Trial; Wounds And Injuries | Soft tissue injuries to the ankle (ankle sprains) are common injuries treated in Canadian emergency departments. An important proportion (up to 40%) of these injuries result in chronic functional limitations that may affect work and leisure activities. However, there is little evidence surrounding the optimal care of these injuries. While evidence exists from studying athletes that physical therapy can be effective in the treatment of ankle injuries, similar treatments have yet to be tested in more general populations, such as those treated in emergency departments. We propose to conduct a randomized controlled trial in order to assess the efficacy of a physical therapy based intervention among adult patients presenting to a hospital-based emergency department with acute ankle sprains. We will recruit approximately 500 patients for study, randomize them to one of two treatment areas (usual emergency care plus physical therapy vs. usual emergency care alone), then follow both groups and compare patient experiences with functional limitations up to six months post-injury. This trial is important because: 1) despite being common, there is little evidence surrounding the optimal treatment of ankle sprains in emergency department settings; 2) existing research from other clinical settings (e.g. sports injury management) suggests that physical therapy is beneficial; 3) there is a paucity of published randomized clinical trials of physical therapy interventions for the acute treatment of ankle sprains in the general population; 4) we expect that the findings will inform clinical practice for both emergency physicians and allied health professionals including physical therapists; 5) we believe the potential to reduce the burden of disability from this injury exists and this may be accomplished with early intervention | 3 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170575&lang=en |
| 170581 | Can Valacyclovir Delay the Need for Initiation of HIV Treatment in HIV-Infected Individuals with Asymptomatic Herpes Simplex Virus Type 2? | Walmsley Sharon L | Walmsley, Sharon L | University Health Network (Toronto) | Ontario | Canada | 200809 | 4461444.0 | Randomized Controlled Trials | Randomized Controlled Trials | Clinical | Infection and Immunity | Herpes Simplex Virus Type 2; Hiv/Aids; Randomized Controlled Trial; Valacyclovir | Highly active antiretroviral therapy (HAART) has drastically reduced the morbidity and mortality associated with HIV infection, and transformed HIV from an invariably fatal disease into a manageable, chronic condition. However, the inconvenience, high cost, potential side effects, and significant risk of developing drug-resistant HIV associated with taking daily, lifelong HAART make the potential delay of HAART initiation an extremely desirable goal for HIV-infected individuals. Suppression of herpes simplex virus (HSV)-2 co-infection may provide a novel therapeutic strategy for achieving this goal. HSV-2 is among the most common co-infections seen in persons infected with HIV, with rates of up to 52-95%. This co-infection is associated with increased blood levels of HIV, a major predictor of HIV disease progression, even when the person has no herpes symptoms. Medications such as valacyclovir that suppress herpes can also decrease blood levels of HIV, but the potential long-term clinical benefits of this drug have not been adequately studied. It is thus hypothesized that valacyclovir could slow HIV disease progression and prolong the period of time before a co-infected person needs to initiate HAART. This research has been designed to answer this important question through a randomized, placebo-controlled, multi-centre clinical trial. The study will enroll 480 HIV, HSV-2 co-infected individuals over two years from clinics participating in the Canadian HIV Trials Network (CTN) and from the HIV/AIDS Clinical Research Centre of the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. Each participant will be randomly assigned to either valacyclovir or an identical-appearing placebo twice daily, and will be followed up with routine medical assessments and blood tests over 3 additional years. The primary goal is to determine whether patients using valacyclovir can delay initiation of HAART by at least 9 months, compared to those taking placebo. | 6 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170581&lang=en |
| 170582 | The OSCILLation for ARDS Treated Early (OSCILLATE) Trial | Meade Maureen O | Meade, Maureen O; Ferguson, Niall D | McMaster University | Ontario | Canada | 200809 | 3791391.0 | Randomized Controlled Trials | Randomized Controlled Trials | Clinical | Circulatory and Respiratory Health | Acute Respiratory Distress Syndrome; Critical Care; High Frequency Oscillation; Mechanical Ventilation; Ventilator-Induced Lung Injury | Acute respiratory distress syndrome (ARDS) is a common and catastrophic complication of critical illness related to burns, motor vehicle accidents, or overwhelming infection. ARDS kills 40-70% of affected patients. Patients with ARDS require life support in the form of a ventilator to breathe for them while their lungs heal. Ironically, ventilators can cause further damage to the lungs. We propose a study comparing 2 methods to protect the lungs from further damage. One method uses standard mechanical ventilators and the other uses a new type of ventilator, called a high frequency oscillator. Building on our experience with a preliminary study that showed that this is feasible, we propose to test whether this high frequency oscillation will reduce the relative risk of dying from ARDS. A total of 1200 patients will be included from 50 intensive care units in Canada and around the world. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170582&lang=en |
| 170584 | Identification and Mechanisms of Novel S100 Protein Interactions | Shaw Gary S | Shaw, Gary S | Western University (Ontario) | Ontario | Canada | 200809 | 752423.0 | Operating Grant | Operating Grants | Biomedical | Genetics | Calcium Signaling; Nmr Spectroscopy; Protein Folding; Protein Structure; Receptor Interaction | Many important biological processes are controlled by calcium. For example, the transmission of nerve impulses, control of vision and stimulation allowing the heart to beat can not occur without calcium. Frequently, the role of calcium is to bind to specific calcium-binding proteins in the cell, which in turn interact with other proteins or molecules to trigger a biological function. Two important proteins that fulfill this role are S100B and S100A10. In the past 2 years exciting new developments have shown that these proteins also possess calcium-independent protein interactions that impact critical biological functions. For example, both proteins have been shown to interact with receptor proteins whose dysfunction can lead to neural disorders such as depression or Parkinson's disease. Further, S100A10 has been shown to be a member of a large multiprotein complex required to close lesions in the cell membrane that result from injury. We are determining the three-dimensional shapes and interactions of two S100-receptor complexes to understand how the S100 protein controls delivery of the receptor to the plasma membrane. Details of these structures and interactions may allow synthetic molecules to be designed that stimulate or disrupt the protein-protein interaction and control neurological disease. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170584&lang=en |
| 170586 | Protein metabolism and insulin resistance in cancer cachexia: a potential anabolic role of leucine | Chevalier Stéphanie | Chevalier, Stéphanie | Research Institute of the McGill University Health Centre | Québec | Canada | 200809 | 374194.0 | Operating Grant | Operating Grants | Clinical | Nutrition, Metabolism and Diabetes | Gluconeogenesis; Insulin Resistance; Leucine; Lung Cancer; Protein Metabolism; Stable Isotope Kinetic Studies | Protein loss, mostly from muscle, is very common in lung cancer and this affects the patients' physical function, response to treatment and quality of life. We propose that cancer patients are losing proteins because they are resistant to the normal stimuli that promote protein retention after a meal, i.e. the hormone insulin and the building blocks of proteins, amino acids. We have developed a complex metabolic test to study this and have reported that protein synthesis was not responding normally to insulin in obese, elderly, and persons with type 2 diabetes. Now we extend our test to lung cancer patients to compare those who are losing weight to those who are not. In addition, we will study whether their liver uses more amino acids to produce glucose, leaving less for muscle protein build-up, and for the synthesis of specific blood proteins with important functions. Finally, a meal rich in leucine, a particular amino acid having shown promising effects on protein retention will be tested, to see if it counteracts the resistance to insulin action. These studies could lead to design better diets and treatments aimed at preventing the loss of essential body protein and muscle in persons with lung cancer and thus improve their quality of life. | 3 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170586&lang=en |
| 170589 | Evaluating cognitive reactivity as a causal risk factor of depressive relapse | Lau Mark A | Lau, Mark A | University of British Columbia | British Columbia | Canada | 200809 | 323985.0 | Operating Grant | Operating Grants | Clinical | Neurosciences, Mental Health and Addiction | Cognitive Reactivity; Cognitive Therapy; Group Therapy; Mindfulness-Based Cognitive Therapy; Mood Induction; Toronto Mindfulness Scale | Depression is a potentially lifelong illness with a high relapse risk. The proposed study extends our research program studying the role of cognitive reactivity as a risk factor for depressive relapse. Cognitive reactivity, the tendency of formerly depressed individuals to experience increased negative thinking when experiencing sad mood, is associated with an increased chance of experiencing a future depressive episode for these individuals. However, whether reducing cognitive reactivity leads to a reduced chance of experiencing a relapse of depression remains to be determined. Results from current and past research programs demonstrate that a psychological, relapse-prevention treatment, mindfulness-based cognitive therapy (MBCT) led to increased mindfulness and increased mindfulness was associated with reduced cognitive reactivity. This establishes that cognitive reactivity can be reduced by MBCT and that mindfulness may be a mechanism underlying reductions in cognitive reactivity. The proposed study will evaluate whether reductions in cognitive reactivity lead to reduced depressive relapse. In addition, it will evaluate whether MBCT, which teaches mindfulness and cognitive therapy (CT) skills, is necessary to reduce cognitive reactivity or whether CT is a sufficient treatment. In this study, formerly depressed individuals at high risk for depressive relapse will be randomly assigned to MBCT or CT or to a relaxation control group. These participants will be assessed as to their degree of cognitive reactivity both before and after the 8-week treatment period and then followed for an 18-month period to determine whether they experience a depressive relapse. This work has the potential to help all Canadians at risk for depressive relapse by leading to the development of more effective depression relapse prevention programs which could potentially lead to reduced rates of depressive relapse and a reduction in the overall prevalence of depression for Canadian | 4 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170589&lang=en |
| 170617 | Development of chemically modified oligonucleotide therapeutics and mechanistic probes | Damha Masad J | Damha, Masad J | McGill University | Québec | Canada | 200809 | 349989.0 | Operating Grant | Operating Grants | Biomedical | Infection and Immunity | Anticancer And Antiviral Therapy; Biochemistry; Gene Target Knockdown; Oligonucleotide Therapeutics; Rnai And Antisense; Structural Studies On Nucleic Acids | RNA interference (RNAi) is a natural cellular mechanism for selectively silencing the expression of genes via targeted mRNA degradation, preventing gene-coded protein production. Synthetic oligonucleotides (ONs) that activate the RNAi pathway have tremendous potential for functional genomics, drug discovery through in vivo target validation, and novel classes of specific gene-silencing therapeutics. Inherent characteristics of ONs have hampered their progression from the laboratory to the clinic to treat diseases. As a result, chemical modification of these molecules to improve their specificity, potency, stability and pharmacodynamics is currently a hot topic and a major focus of our research activities. Our laboratory is developing chemically modified ONs that try to address several identified shortcomings of earlier generation drug candidates. The objectives of this grant proposal are to 1] advance the development of more effective and more specific oligonucleotide-based therapies; and 2] to deepen our understanding of the biochemical properties of key enzymes implicated in the mechanism of action of nucleic acid-based drugs. Thus, this proposal describes the design of novel chemically-modified antisense and small interfering RNA (siRNA); new chemistry that enhances the bioavailability and uptake oligonucleotides to target cells; and the evaluation of oligonucleotides comprising 2'-fluoroarabinose sugars as anti-tumor and anti-viral agents. The experimental plan combines chemical synthesis, physicochemical studies (NMR, CD, UV), cell based assays, etc, all built on a foundation of progress during 2005-2008 in developing modified oligonucleotides as gene silencing agents. The proposed work exposes students to nucleic acid chemistry and biology, analytical skills, and to strategies designed to develop candidate molecules into useful drugs. | 3 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170617&lang=en |
| 170627 | Role of microRNA in Major Depression and Suicide | Turecki Gustavo X | Turecki, Gustavo X | CIUSSS de l'Ouest-de-l'Ile-de-Montréal-Douglas Hospital | Québec | Canada | 200809 | 767298.0 | Operating Grant | Operating Grants | Biomedical | Neurosciences, Mental Health and Addiction | Major Depression; Microrna; Neurobiology; Suicide; Vulnerability | The major objective of this proposal is to identify microRNA differences in prefrontal cortex and hippocampus of depressed suicides compared to controls. MicroRNA are small, noncoding RNA molecules that regulate RNA expression. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170627&lang=en |
| 170631 | Hypoxia alters protein balance in muscle cells: any relation with initiation and development of muscle atrophy in COPD? | Debigare Richard | Debigare, Richard | Université Laval | Québec | Canada | 200809 | 225985.0 | Operating Grant | Operating Grants | Biomedical | Musculoskeletal Health and Arthritis | Akt; Atrogin-1; Cell Culture; Copd; Hypoxia; Proteasome | Muscle wasting is a significant problem in chronic obstructive pulmonary disease (COPD) which is associated with important clinical issues such as decreased functional status, reduced quality of life and increased mortality rate. Although accumulating knowledge reveals that contractile protein degradation is the primary mechanism involved in muscle wasting, factors initiating this process in COPD is still poorly understood. Low blood oxygen levels frequently presents in COPD increasing in severity as the disease progress. Lack of oxygen has been suggested to have the potential to trigger muscle loss in human subjects. In a model of cultured muscle cells, we found that low oxygen levels altered contractile protein homeostasis with a net loss in protein content as a consequence. In this research application, we propose to investigate the relationship between low oxygen levels and inflammation in the initiation of contractile protein degradation and the development of muscle atrophy. Greater understanding of the biochemical mechanisms that are involved in peripheral muscle wasting is important to design successful therapies aimed at reversing or stopping its progression and minimizing its adverse effects. | 3 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170631&lang=en |
| 170640 | Targeting of delta opioid receptors in neuropathic pain: implications for novel therapy | Cahill Catherine M | Cahill, Catherine M | Queen's University (Kingston, Ontario) | Ontario | Canada | 200809 | 500072.0 | Operating Grant | Operating Grants | Biomedical | Neurosciences, Mental Health and Addiction | Behavioural Pain Assessment; Electron Microscopy; Neuro-Glia Interactions; Neuropathic Pain; Opioid Receptors; Receptor Trafficking | While acute pain is uncomfortable and perhaps menacing, it serves a useful purpose in warning an organism of impending harm. In contrast, chronic pain serves no useful purpose, is usually out of proportion to an injury or pathology, and may persist long after healing is complete. A recent National Survey indicated that 3.9 million Canadians (17%) over the age of 15 have chronic pain. Neuropathic pain generally falls under the umbrella of chronic pain and affects 2-3% of the population in North America. Epidemiological studies have demonstrated that 70% of individuals suffering from chronic pain is rated as moderate to severe enough to interfere with normal daily activities and can last for months to years. Consequently, chronic pain imposes a significant burden on society by diminishing the quality of life of patients and their families and also has an enormous impact on healthcare costs, and other expenditures predicted to be over $150 billion annually in the US. However, treatment of neuropathic pain is particularly challenging for physicians, as this pain does not respond well to treatment. In the current research proposal, we will investigate the potential of a novel target (delta opioid receptors) for treating neuropathic pain. | 3 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170640&lang=en |
| 170643 | Sleep and circadian rhythms in the middle years of life | Carrier Julie | Carrier, Julie | CIUSSS du Nord-de-l'Ile-de Montréal - Hôpital Sacré Coeur | Québec | Canada | 200809 | 472764.0 | Operating Grant | Operating Grants | Clinical | Aging | Aging; Brain Imaging; Circadian Rhythms; Electrophysiology; Sleep; Vigilance | The current overwhelming evidence that aging is associated with a significant increase in sleep-wake cycle complaints has important individual, social and economical consequences. Multiple factors, including health problems, side effects of medications and specific sleep disorders, account for this age-related increase in sleep difficulties. However, critical changes in the sleep-wake cycle are also observed in optimal aging, i.e., when people do not suffer from medical, psychiatric or specific sleep disorders. These age-related changes occur as early as the middle years of life. Between the ages of 20 and 60, increasing age is associated with less time asleep, more awakenings during sleep, less deep sleep, and more lighter stages of sleep. With increasing age, sleep is also more vulnerable to challenges such as jet-lag or shift-work. The long term goal of our research program is to understand the mechanisms that underlie age-related modifications of the sleep-wake cycle. In this proposal, we will use innovative brain imaging techniques to evaluate if age-related changes in brain morphology and activity may explain age-related changes in the sleep-wake cycle. The sleep of young (20-39 y.o.) and middle-aged subjects (40-60 y.o.) will studied under habitual and sleep deprivation conditions. This research should provide important answers on how aging impacts sleep oscillations in their role to protect sleep and how age-related changes in the brain during sleep oscillations may underlie changes in vigilance and cognition. The long-term goal of our research program is to develop preventive and therapeutic strategies for the older population based on the mechanisms underlying age-related changes of the sleep-wake cycle. | 4 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170643&lang=en |
| 170644 | Hepadnavirus Pathogenicity in Woodchuck Model of Hepatitis B | Michalak Thomas I | Michalak, Thomas I | Memorial University of Newfoundland | Newfoundland and Labrador | Canada | 200809 | 812265.0 | Operating Grant | Operating Grants | Biomedical | Infection and Immunity | Hepadnaviral Lymphotropism; Hepadnavirus Persistence; Immuology Of Hepadnavirus Infection; Molecular Immunopathogenesis Of Hepadnaviral Infection; Viral Hepatitis; Woodchuck Model Of Hepatitis B | Hepatitis B virus (HBV) is an important human pathogen implicated in a wide range of clinical manifestations, ranging from cirrhosis, liver cancer and hepatic failure to seemingly asymptomatic and undetectable, by current clinical laboratory assays, occult HBV infection. Presently, an estimated 370 million people worldwide suffer from chronic liver diseases caused by HBV, 2 billion have been exposed to the virus and could be infected at low levels, and up to one million die annually because of HBV-induced liver pathology. In Canada, ~270,000 individuals have chonic hepatitis B. There is no effective treatment to completely eridicate the virus and, despite having vaccines, the number of people infected is not declining. The mechanisms governing establishment of persistent HBV infection, chronic hepatitis and virus-induced cancer remain under investigation, although meaningfull progress has been made in some areas. Since HBV infects only humans and higher primates and it cannot be studied simply in cell cultures, appropriate animal models are of primary importance. The woodchuck infected with woodchuck hepatitis virus (WHV) constitutes the most adequate system to study HBV infection and its pathological and epidemiological consequences. This rare experimental system is very well established in the applicant's laboratory. It has been successfully applied during the last two decades to recognize virological, molecular, cellular and immunological aspects of HBV infection, hepatitis B, HBV-induced liver cancer, and anti-HBV therapy. In the current studies, the model will be utilized to further advance knowledge by investigating yet unidentified elements of the natural history of infection, mechanisms of virus persistence, and roles of viral factors and host immune responses in the development and progression of liver disease and disorders of the immune system which seem to be associated with HBV infection. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170644&lang=en |
| 170647 | A National "Patterns of Care" Study in Prostate Cancer Radiation Therapy: Development and Use of Quality Indicators | Brundage Michael D | Brundage, Michael D | Queen's University (Kingston, Ontario) | Ontario | Canada | 200809 | 249374.0 | Operating Grant | Operating Grants | Health systems / services | Cancer Research | National Patterns Of Care; Prostate Cancer; Quality Indicators; Radiation Therapy | Radiotherapy is an important form of treatment for cancer patients and has been shown to be useful in about 50% of patients with cancer. It can be used alone or in combination with chemotherapy or surgery to cure cancer and can help to alleviate pain and other symptoms in patients with more advanced disease. Use of state of the art technology and knowledge has the potential to achieve the best possible outcomes for cancer patients receiving radiation therapy, but only if the knowledge and technology are being used in the best way possible. As part of a larger program aimed at improving cancer outcomes for patients by optimizing the accessibility and quality of radiotherapy in Canada, a national study to look at patterns of care in prostate cancer is being undertaken. The study has two main objectives: 1) To develop a set of Radiation Therapy indicators of quality service that can be used in cancer centres across Canada, and 2) To determine how well Canadian cancer centres meet these quality standards. Since the information that will be collected is very similar to that used in the US, we will be able to compare results not only within Canada but also with our American counterparts. This study will be the first step in developing a standardized Canadian quality assurance program in prostate cancer radiotherapy. | 2 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170647&lang=en |
| 170652 | The pathogenic E. coli type III secretion system and its effectors | Finlay Barton B | Finlay, Barton B | University of British Columbia | British Columbia | Canada | 200809 | 1046030.0 | Operating Grant | Operating Grants | Biomedical | Infection and Immunity | Diarrhea; Enterohemorrhagic E. Coli; Hemolytic Uremic Syndrome; Pathogenesis; Type Iii Secretion; Virulence | Enteropathogenic E. coli (EPEC) are a leading cause of bacterial diarrhea, causing much morbidity and mortality in children worldwide. Enterohemorrhagic E. coli (EHEC; E. coli O157) is a close relative of EPEC which causes "hamburger disease" and hemolytic uremic syndrome (HUS), and was the source of the Walkerton, Ontario outbreak and a major spinach recall. EPEC and EHEC belong to a family of attaching and effacing pathogens that adhere to intestinal epithelial cells, causing a specialized disruption on the intestinal cell surface which mediates disease. This application addresses several fundamental questions pertaining to secreted pathogenic E. coli proteins that are virulence factors. This includes studying the structure and function of the type III secretion system needed to secrete and inject these effectors into host cells, including protein-protein interactions and regulation of secretion. New type III secreted factors will be identified and their contribution to disease studied in a relevant murine infection model. In addition, molecular characterization of the mammalian proteins that these factors interact with will be examined, as will their effects on host cells and in an animal disease model. Collectively, these studies will provide information about disease progression and the role of secreted virulence factors, which can be applied to design therapeutics and vaccines against diseases caused by these pathogens. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170652&lang=en |
| 170657 | Mechanism of Action of the Adenovirus Death Protein E4orf4 | Branton Philip E | Branton, Philip E | McGill University | Québec | Canada | 200809 | 720706.0 | Operating Grant | Operating Grants | Biomedical | Cancer Research | Adenovirus; Cancer Cells; Cell Cycle; Cell Death; Protein Complexes; Protein Phosphatase 2a | For some time we have used human adenoviruses as models to understand the molecular basis of cancer as such studies have provided many critical insights into processes of importance for cancer. In the present project we have identified an adenovirus protein, E4orf4, that kills cancer cells selectively and leaves normal human cells unaffected. We believe that E4orf4, or drugs that mimic its action, may provide novel avenues for cancer therapy and that if we understand exactly how E4orf4 works that we may be able to develop a drug that mimics its effects. In the present proposal we will examine details of the cancer cell killing specificity of E4orf4, examine the mechanism by which it kills, and begin the process of using this information in drug development. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170657&lang=en |
| 170663 | Control of cell proliferation and survival. | Litchfield David W | Litchfield, David W | Western University (Ontario) | Ontario | Canada | 200809 | 622698.0 | Operating Grant | Operating Grants | Biomedical | Cancer Research | Apoptosis; Caspase; Cell Survival; Protein Kinase; Signal Transduction | The recent success of Gleevec (imatinib) which targets the BCR-Abl protein kinase for the treatment of chronic myelogenous leukemia provides proof-of-principle for molecular-targeted therapy directed against a protein kinase. Spurred by the success of Gleevec, this research project is focused on a close relative of BCR-Abl known as protein kinase CK2 that is present at abnormally high levels in many tumours and that causes cancer when its levels are increased in mice. We want to determine how CK2 allows cancer cells to acquire enhanced survival as compared to normal cells so that this information can be used to devise molecular-targeted therapies directed at the precise defects that underlie the disease. Over the past several years, our group has performed extensive research on the CK2 group of protein kinases with studies focused on defining how CK2 is regulated in cells and defining how CK2 is involved in the control of cell growth and survival. To capitalize on our expertise, we will use knowledge of the three-dimensional structure of CK2 together with computational and experimental approaches to determine how CK2 modulates the regulatory networks that control cell survival. By understanding how CK2 promotes the survival of cancer cells, we envisage that it will be possible to devise novel CK2-targeted therapies that will be effective for those forms of cancer or leukemia that are characterized by increased levels of CK2. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170663&lang=en |
| 170666 | Mechanisms and consequences of three-dimensional (3D) nuclear remodeling of telomeres in cancer | Mai Sabine | Mai, Sabine | University of Manitoba | Manitoba | Canada | 200809 | 388829.0 | Operating Grant | Operating Grants | Biomedical | Cancer Research | C-Myc; Genomic Instability; Spectral Karyotyping; Telomere And Interphase Nucleus; Three-Dimensional Imaging; Tumor Initiation | We have previously shown that the structural order of the cell is changed when cells become tumor cells. To document this, we have studied one central component in the cell that is called the nucleus. The nucleus contains our genetic information. The structural order of the nucleus is what differentiates a normal cell from a cancer cell. In other words, if the order of this structure is compromised, the cell is not normal anymore. We propose to identify mechanisms through which the structural organization of the nucleus can be changed. We will define the changes that are required for cells to become cancerous. This study is highly relevant for our understanding of early changes that lead to cancer. In the future, we propose to use the defined changes for the screening of patients at risk of cancer, for monitoring of their disease progression and of treatment success. | 3 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170666&lang=en |
| 170676 | Signal integrators for monoamine neurotransmission | Beaulieu Martin | Beaulieu, Martin | Université Laval | Québec | Canada | 200809 | 888560.0 | Operating Grant | Operating Grants | Biomedical | Neurosciences, Mental Health and Addiction | Akt/Glycogen Synthase Kinase 3; Dopamine; Neuropsychiatric Disorders (Depression; Psychopharmacology; Schizophrenia); Serotonin; Signaling | Monoamine neurotransmitters such as dopamine and serotonin are involved in the regulation of multiple brain functions including movement, mood and reward. Because of this, the biological mechanisms that mediate the action of these neurotransmitters have become major therapeutic targets for the management of neuropsychiatric disorders such as depression, Parkinson disease and schizophrenia that collectively affect large segments of the population. At the cellular level, monoamine neurotransmitters exert their action by stimulating receptors that modulate behavioral responses by initiating cascades of biochemical events-also designated as signaling pathways. Most psychotropic drugs are designed to affect either the level of neurotransmitters or specific subclasses of receptors. However these drugs have a poor specificity of action leading to the development of multiple unwanted side effects. Furthermore, efficient treatment of psychiatric disorders often involves the modulation of more then one neurotransmitter at a time. A better understanding of the regulation of signaling pathways by monoamine neurotransmitters may allow unraveling the interplay between these different neurotransmitter systems. In turn, this could results in the development of better therapeutic agents having lesser side effects. Our work and the work of others have identified molecules from the Akt/GSK3signaling pathway as important mediators of the action of both dopamine and serotonin on behavior. In this project we propose to use an integrated approach involving the biochemical and behavioral characterization in genetically modified animals models to decipher the role of these signaling pathways in the regulation of brain functions. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170676&lang=en |
| 170677 | Mechanism of calpain mediated dopamine loss in PD. | Park David S | Park, David S | University of Ottawa | Ontario | Canada | 200809 | 882625.0 | Operating Grant | Operating Grants | Biomedical | Neurosciences, Mental Health and Addiction | Calpains; Cdk5; Dna Damage; Dopamine; Neuronal Death; Parkinsons Disease; Substantia Nigra | Parkinsons disease is a progressive neurodegenerative disorder characterized by loss of specialized brain cells which produce the brain molecule dopamine. Loss of these cells results in impaired movement which is one of the significant, although not exclusive, symptoms of the disease. Recent efforts in this field have focused on understanding the regulatory processes which control this type of death. We have recently shown that a specific protease called calpains may participate in this process. The present research is geared towards determining the causal nature of calpains in this process and determining how calpains mediate this degeneration. In understanding these pathways, we hope to, not only gain an appreciation for an important basic biological process, but also devise therapeutic strategies to treat Parkinsons disease. | 5 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170677&lang=en |
| 170691 | The Clinical Investigation of Fracture Risk in Patients with Chronic Kidney Disease | Jamal Abida Sophina | Jamal, Abida Sophina; Lok, Charmaine E | University Health Network (Toronto) | Ontario | Canada | 200809 | 415339.0 | Operating Grant | Operating Grants | Clinical | Musculoskeletal Health and Arthritis | Chronic Kidney Disease Clinic; Clinical Determinants Of Fracture In Chronic Kidney Disease; Clinical Measures Of Bone Quality; Clinical Measures Of Bone Quantity (Bmd Testing) | Broken bones (fractures) due to osteoporosis "or thinning of the bones" are common in men and women with kidney disease. For example, just over half of men and women with kidney failure needing dialysis will have a fracture. Fractures can cause sickness and even death. The number of Canadians requiring dialysis is increasing dramatically and, as such, the number of Canadians at risk for fractures is also increasing. By preventing fractures in dialysis patients we could dramatically improve quality of life, reduce death, and decrease health care costs. The first step in preventing fractures is to identify men and women with kidney disease at high fracture risk before they start dialysis. Our study will identify and follow (for 2 years)200 patients with kidney disease to determine who is at risk for developing fracture and what tests can identify those at highest risk. This study is the first step in reducing the death and disability due to fractures in patients with kidney failure. | 3 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170691&lang=en |
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CREATE TABLE [cihr_grants] ( [external_id] TEXT PRIMARY KEY, [title] TEXT, [project_lead_name] TEXT, [co_researchers] TEXT, [institution] TEXT, [province] TEXT, [country] TEXT, [competition_year] TEXT, [award_amount] TEXT, [program] TEXT, [program_type] TEXT, [theme] TEXT, [research_subject] TEXT, [keywords] TEXT, [abstract] TEXT, [duration] TEXT, [source_url] TEXT );