Congratulations to Dr. Emil Schemitsch, Chair/Chief, Department of Surgery, and Dr. David O'Gorman, Scientist, Assistant Professor, Division of Plastic & Reconstructive Surgery, on their successes with CIHR in the recent operating grants competition.
Project Title: The DECIPHER Study: DEterminants of Function and Clinically Important outcomes in Proximal Humerus Fractures in the Elder Population: A National CohoRt
PI(s): Dr. Emil Schemitsch, Dr. Michael Mckee, and Dr. Aaron Nauth
Dr. Schemitsch and his colleagues will receive $100,000. Divsion of Orthopaedic Surgery members, Dr. Abdel-Rahman Lawendy, Associate Professor, and Dr. David Sanders, Professor, are co-investigators on the project.
Abstract: Shoulder fractures are increasingly common in older adults, and result in considerable limitations in function and quality of life. Unfortunately, the best way to treat shoulder fractures is currently one of the most debated areas of trauma research. Existing clinical studies comparing various methods of surgical and non-surgical management have reported conflicting results. These studies have had limited numbers of patients, involved single centres, and used inconsistent treatment methods and inclusion/exclusion criteria. Therefore, there is insufficient evidence supporting any one treatment type, and a poor understanding of what factors influence the outcomes that are important to patients, making decisions regarding treatment difficult. We propose to establish DECIPHER, the first nation-wide, multicentre observational study with at least 650 fully characterized patients with the ultimate goal of determining what specific factors influence patient important outcomes. Additionally, we will answer important questions concerning whether treatment strategies should be different in older patients (70 years and older) or in patients with more associated medical disorders, and the best method of rehabilitation following treatment. Patients 50 and older with shoulder fractures will be recruited from approximately 11 centres across Canada. Patients will be followed for two years, during which time patient function and quality of life centered outcome measures will be collected at regular intervals. A cost analysis will be conducted to determine the impact of treatment type on patient and healthcare system costs. The information collected through DECIPHER will not only help guide treatment decisions, but serve as a stepping stone for future studies to determine the best treatment strategy for managing these difficult and prevalent injuries.
Project Title: The roles of WT1 in fibrosis development
PI(s): Dr. David O'Gorman
Dr. O'Gorman will receive $397,540 throughout a period of four years. Dr. Bing Gan, Professor, Division of Plastic & Reconstructive Surgery, is a co-investigator on the project.
Abstract: Loss of tissue or organ function due to abnormal scarring, also called fibrosis, contributes to about 40% of all deaths in the Western world. Once fibrosis has commenced, none of the available treatments consistently prevent its progression or recurrence. To design more effective treatments, we need to gain a better understanding of this disease process and to identify the events that cause normal tissue and organ repair to deviate toward fibrosis. The focus of this application is a gene called WT1. This gene is well known for its roles in promoting cancers. Increased activity of this gene has been recently noted in non-cancerous fibroses of the lung, liver, heart and hand. We have found that molecules secreted by the immune system potently induce the activity of WT1 and we hypothesize that chronic exposure to these molecules induces sustained WT1 activity, disrupts normal tissue repair and enhances fibrosis development. Rather than testing this hypothesis in animals that do not normally develop fibrosis, we will take the novel approach of "bioengineering" the fibrotic process in our laboratory using cells derived from human tissues. This approach allows us to use genetically identical cells from the same patients before and after fibrosis development. As members of the Roth|McFarlane Hand and Upper Limb Centre, the largest specialist surgical unit of its kind in Canada, we have direct access to the tissues we need to maintain these models. The aims of this project are to determine if increased WT1 activity 1)Disrupts tissue repair processes, and 2)Enhances fibrosis progression. If increased WT1 activity induces fibrosis, there is real potential to target it with treatments and prevent fibrosis. Treatments that target WT1 in cancers have already been proven to be safe and clinical trials of these treatments are currently underway. This project will determine if it is feasible to cross-purpose these treatments to prevent tissue and organ fibrosis.