Grant Recipients » 2009
The Manitoba Medical Service Foundation has been awarding Research Grants to researchers and students since 1971, and over $17.5 million has been donated to furthering this cause.
Bioavailability studies of selected components of flaxseed in plasma of patients with peripheral arterial disease (PAD).
Dr. M. Aliani
$12,500
$12,500 (U of M)
Nutritional interventions are gaining in popularity as legitimate therapeutic strategies to combat cardiovascular disease. A common dietary intervention used to alter cardiovascular disease today is the supplementation of the diet with ω-3 fatty acids. Flaxseed is a plant source for these fatty acids and will also offer a source of fibers which do not exist in animal sources of these fatty acids. The flaxseed fibers are metabolized in the body and generating metabolites which are believed to be effective as a lipid-lowering and antioxidant agent.
This MMSF application intends to investigate the bioavailability of flaxseed selected fiber’s metabolites in plasma of patients with peripheral arterial disease enrolled in the human clinical trial with flax conducted at St. Boniface Hospital.
Investigation of fish oils, aspirin, and aspirin-triggered lipoxin as protective modulators of inflammation in murine model of acute graft versus-host disease (GVHD).
Dr. G. Cuvelier
Dr. C. Ellison
Dr. C. Oleschuk
$25,000
Blood and marrow transplant (BMT) therapy involves the collection of stem cells from a healthy donor (the “graft”), with infusion of these stem cells into another individual with a disease (the “host”). In clinical practice, BMT is a potentially curative treatment for a variety of malignant and non-malignant diseases that are otherwise fatal. A number of complications limit the success of BMT, with acute graft-versus-host disease (aGVHD) being the most significant complication contributing to morbidity and mortality. Acute GVHD occurs when immunologic cells from the graft recognize recipient tissues as foreign, inciting an immunologic attack against the host. Systemic inflammation underlies both the initiation and maintenance of aGVHD.
Our research focuses on ways to reduce aGVHD through the use of therapies that reduce inflammation in the early post-transplant period. Using a mouse model of lethal aGVHD we are testing if supplementing the diet before and after BMT with omega-3 polyunsaturated fatty acids, specifically eicosapentaenoic and docosahexaenoic acid commonly found in fish oils, induce the production of protective lipid mediators known as resolvins and protectins that actively reduce inflammation and heal damaged tissues. Secondly, we are testing an “old drug”, aspirin, for new anti-inflammatory properties involving the production of lipid mediators known as aspirin-triggered lipoxins. Thirdly, we are directly testing an aspirin-triggered lipoxin, 15-epi-lipoxin A4, as a novel anti-inflammatory therapeutic. Protective responses against aGVHD, improvement in survival after BMT, and immune modulation away from a Th-1 immune response are the expected outcomes. These experiments have been designed to set the stage for translation into a clinical trial in human BMT subjects.
Insulin resistance and the regulation of myocardial calcium-transport in models representative of the Type 2 diabetic heart.
Dr. T. Duhamel
$25,000
Calcium is an important signaling molecule involved in the regulation of cardiac contraction. Notably, the diabetic heart is characterized by cardiac dysfunction, which may be attributed, at least in part, to a loss of calcium regulation. Accordingly, my laboratory focuses particular attention to understand the basic biological mechanisms to explain how diabetes adversely influences the movement of calcium within the heart and, ultimately, contributes to the development of diabetes-induced heart disease. There is some evidence indicating that insulin promotes the co-localization of insulin receptor substrate (IRS) proteins with sarco(endo)plasmic reticulum calcium-ATPase (SERCA2a) proteins in the healthy heart. However, the physiological significance of this protein interaction has not yet been determined. Furthermore, it is not yet known if diabetes adversely influences this process. Therefore, our research program will determine if insulin resistance, which is the primary clinical problem for patients diagnosed with type 2 diabetes, will prevent the interaction of IRS proteins with SERCA2a proteins and, thereby, contribute to the loss of cardiac contractility in a cell culture model representative of the type 2 diabetic heart. Information derived from this research program has the potential to discover a novel pathological mechanism to explain how diabetes impairs calcium transport and contractility in the diabetic heart and may provide the basic information required to guide the future development of novel therapeutic interventions to prevent diabetes-induced heart disease.
Phenotypic and genotypic characterization of patients with Ritscher-Schinzel Syndrome.
Dr. A. Elliott
$12,500
$12,500 (MICH)
Approximately 3% of babies are born with a birth defect that requires medical attention. Some babies are born with multiple defects. Ritscher-Schinzel syndrome (RSS) is a genetic syndrome and affected children have malformations involving the heart, brain and face. We have identified a group of Manitoba paediatric patients who have RSS. Routine testing has not determined the cause of their disorder. This study will use a combination of two cutting edge clinical and molecular technologies to further characterize RSS. The clinical approach will utilize noninvasive three dimensional (3D) imaging analysis of the facial surface. This method has been successful in the delineation of the craniofacial changes in numerous genetic syndromes. RSS is presumed to follow an autosomal recessive pattern of inheritance since some parents of affected children have been related by blood and there have families reported with more than one child affected. By studying RSS families with a powerful new research tool, called “Single nucleotide polymorphism” (SNP) array analysis, we will be able to identify genetic regions of interest and eventually uncover the underlying genetic changes.
A randomized double-blinded, placebo-controlled, cross-over trial assessing the effect of tadalafil (Cialis) on the cardiovascular response in men with complete spinal cord injury at or above the sixth thoracic level.
Dr. K. Ethans
Dr. A. Casey
$10,000
$15,000 (HSCF)
Erectile Dysfunction is the inability to achieve and/or maintain an erection sufficient for sexual intercourse,and is a common issue among men with spinal cord injury. The main treatment for erectile dysfunction in men with spinal cord injury is a class of drugs called phosphodiesterase type-5 (PDE -5) inhibitors. Sildenafil (Viagra) was the first PDE-5 inhibitor available, and is effective up to 4 hours. More recently available is tadalafil (Cialis), which is longer-acting, being effective for obtaining erections for up to 36 hours after taking. Both of these medications have been shown to be helpful in men with spinal cord injury. Our concerns are that the side effects from Cialis would last much longer than Viagra since Cialis is in the body much longer. This was recently shown in a study of men that were not spinal cord injured, where it was found that the duration of the side effects was significantly longer with Cialis (14.9 hours) vs Viagra (3.9 hours). People with spinal cord injury often have low blood pressure, which can cause light-headed or passing out. This occurs particularly in people with spinal cord injury at the chest level or above. It is also known that PDE-5 inhibitors can cause low blood pressure. Our concern is that the low blood pressure that people with spinal cord injury have can be greatly exaggerated with the PDE-5 medications. We did show this with earlier work with the shorter acting Viagra, where we found a significant drop in blood pressure in men with spinal cord injury that took that medication. However, the drop only lasted up to 4 hours. We are suspecting that Cialis, being a much longer lasting medication, may cause the same drop in blood pressure, but the drop may last up to a day or more! There are obvious safety issues here if someone has to deal with drop in blood pressure for an extended period of time after taking a medication, thus we feel it is important to clarify whether indeed this blood pressure drop does happen with Cialis in the spinal cord injured population. However this medication is being prescribed to men with spinal cord injury, thus we need to be sure it is being prescribed safely and with full knowledge of potential side effects.
Mutations in the MeCP2 gene result in white matter defects that occur in childhood disorders of the brain.
Dr. E. Frost
Dr. M. Namaka
$25,000
Formation of the white matter of the brain is dependent on the interactions of many different molecules during gestation. We have identified a novel role for a molecule that was previously thought to only regulate neurons. By further understanding the role that this molecule plays during development of the white matter we hope to better understand the cause of many brain disorders including autism, Schizophrenia and mental retardation. We will use an animal model which does not express the protein to identify its exact role in brain development.
Combining clinic data on fetal alcohol spectrum disorder (FASD) with administrative data on health, education and social services.
Dr. A.
Hanlon-Dearman
Dr. M. Brownell
Dr. A. Chudley
$12,500
$12,500 (MICH)
Fetal Alcohol Spectrum Disorder (FASD) includes a range of conditions resulting from prenatal alcohol exposure, which can cause intellectual disabilities as well as behavioural, emotional and social difficulties. A lack of good information on who has FASD in Canada has made it difficult to determine how common the condition is, but estimates suggest that at least 1 in every 100 births is affected by this condition, and in some countries and small populations within Canada, rates are much higher. There is also little information on what happens to children with FASD once they are diagnosed with the condition. This project will combine information from a provincially centralized FASD assessment clinic in Manitoba, the Manitoba FASD Centre, with health and social services administrative data available on all residents of the province. The objective of this project is to examine rates of health and social outcomes for children identified with FASD. This information would help determine what services these children are accessing and help answer questions related to the burden of this disorder on health and social services systems. By making use of two unique existing sources of information this project has the potential to inform policies as well as provide a valuable resource for subsequent research on children with FASD.
Hormone use, estrogen receptor expression, and survival of women with non-small cell lung cancer: A Manitoba perspective.
Dr. G. Harding
Dr. S. Navaratnam
Dr. L. C. Murphy
Dr. A. Demers
$12,500
$12,500 (WF)
Lung cancer is the most common cause of cancer death in the world. Research indicates that there are gender differences in non-small cell lung cancer (NSCLC) incidence and survival. The mechanism for this gender differences is unclear. Scientists feel estrogen may play a role. There is little published literature that exists on the specific study and mechanisms of actual estrogen hormone receptors on lung cancer cells, hormone replacement therapy, oral contraceptive therapy, and NSCLC. Given the low survival, high incidence, and high cost of treatment, it would be of significant importance to identify risk and prognostic factors for NSCLC survival. Towards this end, we will analyze a large group of female NSCLC patients in Manitoba over the periods of January 1, 2000 to December 31, 2007 using the Manitoba Cancer Registry. This group will be further subdivided based upon a history of use vs. non-use of hormonal replacement therapy use, oral contraceptive use, and differences in survival will be compared. We will also take actual archived tumor samples from these women and look for the presence of estrogen receptors in the lung cancer tissues. We will then study possible connections in patient survival, history of hormone replacement therapy use, oral contraceptive use and the presence of estrogen receptors in the lung cancer tissues. We expect to find a group of women within our whole group that exhibit a survival difference in their cancers based on the above factors interacting with each other.
Quetiapine, as a novel therapeutics in Alzheimer's disease.
Dr. J. He
$10,000
$15,000 (HSCF)
Neuroprotective mechanisms of atypical antipsychotics in the treatment of Alzheimer’s disease
Alzheimer’s disease (AD), a neurodegenerative disorder, comprises cognitive and memory deterioration, progressive impairment of activities of daily living, and several neuropsychiatric symptoms. Atypical antipsychotics including quetiapine and olanzapine, effectively alleviate positive and negative symptoms, as well as cognitive impairment in schizophrenia patients. Atypical antipsychotics are widely used to treat psychosis, aggression, and agitation associated with AD. Although there is increasing evidence on the neuroprotective effects of atypical antipsychotics, it is not known if it can reverse the pathological alterations and memory impairment in the AD. This proposal will evaluate the action of atypical antipsychotics in the AD brain in the mouse model. We hypothesize that atypical antipsychotics have neuroprotective effects that can prevent and treat symptoms of AD in a transgenic mouse model of AD. AD transgenic mice will be chronically administrated by quetiapine or olanzapine, and then the cognitive and emotional behaviours, and brain pathology and neurochemistry of mice will be evaluated. This project will be useful for addressing the pathophysiology of AD and the mechanisms underlying the possible preventive and therapeutic effects of atypical antipsychotics in AD, developing novel treatment strategies in the treatment of AD, thus improving quality of life for people suffering from AD.
The relationship between injury to surgery (I-S) time and the incidence of secondary joint injury in an ACL injured population.
Dr. J. Leiter
Dr. P. MacDonald
Dr. J. Peeler
$24,000
The study has been designed to determine if the length of time between a knee injury, specifically anterior cruciate ligament rupture, and surgery is associated with additional damage to the knee joint. This study will provide evidence as to the time frame of when ACL reconstruction surgery should be performed to prevent further damage to the injured knee that may leave individuals at a greater risk of developing osteoarthritis in the future.
Does geography influence the treatment and outcomes of colorectal cancer in the Province of Manitoba?
Dr. A. McKay
Dr. D. Wirtzfeld
Dr. D. Turner
$12,000
$12,500 (WF)
Introduction: Our research team is planning to analyze whether the place that people live in Manitoba has any impact on the type of care that they might receive for colorectal cancer (CRC). This study will look for differences in access to medical care, differences in the quality of medical care, differences in the actual medical treatments that are offered, and differences in survival and recurrence rates for Manitobans with CRC.
Project Description: This study will look at the treatment received by all Manitobans with CRC between Jan 1, 2004 and Dec 31, 2006 by using data from the Manitoba Cancer Registry. This data will be linked to other databases that are maintained by Manitoba Health in order to perform the study.
Impact and relevance: With the large geographic impositions faced by many cancer patients in the Province of Manitoba, it is very important to know if this translates into differences in access to care, quality of care, and important outcomes such as survival and recurrence after treatment for CRC. This research will be of great interest for physicians across Canada and abroad, since these same issues are encountered in all provinces in Canada and in many other countries around the world. While this study will not be able to determine the exact reasons why such regional differences might exist, it would be important to demonstrate whether these differences do exist. This could highlight areas where additional research aimed at finding the cause of these differences and aimed at correcting these discrepancies is needed. This could have a tremendous impact in improving the healthcare of all Manitobans, not only the hundreds who are afflicted with CRC every year.
Investigation into viral evasion of the human innate immune response to infection.
Dr. S. A. McKenna
$25,000
The plan is to investigate how viruses specifically inhibit the human innate immune response to infection via biochemistry and structural biology approaches. Unfortunately, viruses can subvert the innate immune response by encoding protein and nucleic acid molecules that directly inhibit PKR (RNA dependent protein kinase), allowing viral replication and the disease state to persist. The goal of the current proposal is to understand the molecular mechanism of how inhibitors of PKR allow evasion of the host-cell immune response. We propose to examine, at the molecular level, the features that govern the interaction between PKR and its viral inhibitors using innovative biochemistry and structural biology approaches. Four inhibitors will be examined from different viruses; two viral proteins and two viral nucleic acid molecules. Viral inhibitors will be produced, purified, and investigated for their inhibitory potency in order to determine features central to inhibition. High-resolution images of PKR in complex with viral inhibitors will be generated using a combination of structural biology approaches. Together, these results are anticipated to significantly expand the fundamental understanding of how viral infection is sensed by human cells and will thus be of importance to both clinical and academic health scientists. Furthermore, the results obtained will provide the foundation for the design of novel therapeutics to combat viral infection.
Magnetic nanoparticles for enhanced drug delivery to the brain.
Dr. D. W. Miller
Dr. J. Van Lierop
Dr. T. Hegmann
$25,000 (MMCF)
One of the major challenges in treating various diseases of the brain is the inability to deliver the drug or therapeutic agent to its site of action. This is due to the restrictive nature of the brain capillary endothelial cells that form the blood-brain barrier. The overall objective of the current research project is to develop magnetic nanoparticles that can be used as drug carriers to enhance the delivery of drugs to the brain. These small, iron oxide containing particles, around 10-150 nanometers in diameter, will be engineered to penetrate the blood-brain barrier through the use of specific chemical modifications to the outside surface of the particle and by the application of magnetic fields. The current research project will examine the transport and permeability properties of various magnetic nanoparticle formulations in cultured brain capillary endothelial cells under normal conditions and following application of magnetic fields of varying intensity. It is anticipated these studies will ultimately lead to a drug delivery platform for the treatment of brain disorders including stroke, brain tumors and neurodegenerative diseases.
The efficacy of rTMS in treatment of obsessive compulsive disorder, a pilot study.
Dr. M. Modirrousta
Dr. M. Enns
Dr. J. Sareen
$25,000
Obsessive Compulsive Disorder (OCD) is a devastating disease characterized by obsessions, which are recurrent unwanted intrusive thoughts and compulsions, which are repetitive and ritualistic behaviors related to the obsessive thoughts. Despite the available therapies, only one fifth of the patients achieve full remission and two thirds will continue to experience symptoms. We will investigate the effect of a new non-invasive technique of brain stimulation, repetitive Transcranial Magnetic Stimulation (TMS), in treatment of OCD. rTMS has been successfully used for treatment of refractory depression. Yet its efficacy for treating anxiety disorders including OCD is unknown. This study could result in a much needed new treatment option for OCD.
The generation and characterization of an in vitro culture system to expand distinctive human mammary epithelial progenitor cells.
Dr. A. Raouf
$25,000
We now understand that human breast tumours are maintained by rare cancer stem cells in the tumour. This concept suggests that while the current therapies may eradicate most of the tumour cells, they might not eliminate the more relevant cancer stem cells, which can slowly generate new tumours. This concept also suggests that normal stem cells are important cellular targets in the initiation and recurrence of breast cancer and investigating the mechanisms that regulate the normal functions of these primitive cells and how these may be altered to produce tumours is important. To this end, we have developed methods for isolating normal human breast stem cells but the further study of these cells is hampered by the small numbers that they can be isolated. This project seeks to develop a cell culture system that enables the expansion of human breast stem cells in petri dishes in such a way that their unique biological functions are preserved. This system will greatly facilitate the study of breast stem cell functions in health and as source of breast cancer stem cells. Ultimately, this research can facilitate the development of more effective and possibly curative breast cancer therapies.
Understanding the biological differences between juvenile and adult patients undergoing orthodontic treatment.
Dr. W. J. Rody Jr.
Dr. G. Nogueira
Dr. W. Wiltshire
$20,000
Is it safe to move teeth in old patients? Why is the response to orthodontic treatment slower in adults than in juveniles? Are the adults more prone to side effects during tooth movement? These are questions that usually come up to the mind of laypersons seeking orthodontic care. Despite the controversies, a tremendous increase in the demand for adult orthodontic therapy was seen in the past decades. Therefore, the present study will be undertaken to investigate the biological mechanisms underlying the effect of age on tooth movement, as well as to consider any implications of the findings for clinical procedures and decision-making. Instead of using conventional methods, such as x-rays, the differences between young and old patients will be assessed by looking at proteins expressed in the fluid that comes out from the gums during orthodontic treatment. This novel approach could potentially offer advantages of sensitivity, non-invasiveness as well as no radiation exposure.
A simple urinary test to predict hospitalization for congestive heart failure.
Dr. M. Sood
Dr. S. Zieroth
$25,000
Numerous patients with heart failure also develop kidney disease. We are investigated whether a simple urinary test can predict worsening heart function, kidney function and the need for hospitalization in heart failure patients.
Vascular events in noncardiac surgery patients cohort evaluation study and thoracic substudy (T-VISION).
Dr. S. Srinathan
Dr. D. Funk
Dr. C. Ramsey
$25,000
The VISION study will answer three important questions. First, what is the risk of a heart attack, stroke or blood clots in adult patients who are undergoing surgery (except heart surgery)? Second, what specific factors in an individual patient predict those at risk of having these events after surgery? Third, does a specific blood test help us to identify those patients who are having a heart attack, but do not have symptoms? To answer these questions we will follow 40,000 patients around the world (2000 – 3000 in Winnipeg) who are undergoing surgery for one year after their operation. The T-VISION substudy will specifically examine all patients undergoing lung surgery world wide as they are likely to have a higher risk of these events occurring. This information will help make these operations safer.
Development of gene-loaded nanoparticles and collagen scaffolds for bone regeneration.
Dr. M. Xing
$25,000
Estimates are that there will be about 6 million Canadians over age 65 in 2016 and by 2026, one in five Canadians will have reached age 65. No other area in the healthcare of the elderly is more complex than orthopedics. Important research areas include bone repair and reconstruction. Research will develop implants for bone regeneration based on nanomedicine, biomaterial scaffolds and rat mesenchymal stem cells. Specifically, (1) composite scaffolds comprised of collagen, hydroxyapatite, and silk fibroin will be designed and their bioactivity, porosity and mechanical stability investigated. (2) Nanoparticle non-viral vectors will be prepared from biopolymers for the delivery of DNA encoding BMP-2. (3) The interaction between mesenchymal stem cells and the scaffold will also be investigated. The research is expected to lead to the development of products to be used in clinical practice for the repair of bone defects.
Continue reading the next page: Grant Recipients » 2008