Optimization of Trauma systems

Every year approximately 400,000 British Columbians suffer a traumatic injury — the leading cause of mortality and morbidity in Canada. The development of trauma systems to improve the access of injured patients to timely, and often life saving care is a health care priority. Unfortunately, access to timely and appropriate trauma care is not universal in BC. For example, injured patients in rural communities typically face economic, social and geographical barriers to care. In contrast, injured patients in urban communities are typically in close proximity to several hospitals; however, the trauma capabilities within in each hospital are highly variable, so choice of hospital may impact survival. This team of trauma surgeons, trauma care providers, geographers and epidemiologists is building a comprehensive dataset to investigate the performance of, and identify gaps within, the delivery of trauma care in rural and urban communities. The team’s goals will be to create evidence-based solutions where population vulnerabilities exist, and increase the reach and capability of the BC’s trauma system to address disparities in trauma outcomes across the province.

Bioinformatics of sequence indels: Novel applications for protein network analysis, drug target identification and drug development

Infectious diseases continue to be a huge threat worldwide. The effectiveness of current antibiotics is declining as many life-threatening bacteria have developed resistance to existing drugs, giving rise to the need for a new generation of antibiotics. An important factor responsible for emerging bacterial resistance is that conventional antibiotic drugs are designed to disable proteins on bacteria that allow it to infect host cells. These particular proteins mutate readily, which enhances their potential to develop resistance mechanisms against antibiotic treatment. An alternative strategy in antibiotic development would be to target “conserved” proteins – fundamental proteins that are resistant to mutations, because they perform essential functions that keep the bacteria alive. Michael Hsing’s research is focused on developing antibiotics that selectively target conserved and essential proteins in pathogens. To do this, he is investigating the important biological phenomenon of protein insertions and deletions (referred to as indels) and combining this approach with the latest computational tools to develop novel antibiotics that are more rapid and effective than the conventional approach. His goal is the development of an effective and economical method of developing antibiotic drugs to treat existing and emerging pathogens.

The biological role of bone marrow-derived keratinocyte precursor cells in wound healing

Skin, which is the most extensive organ in the human body, performs multiple vital functions. Wounds to this organ, whether chronic or acute, are a serious threat because they leave the body open to infection. That’s why burns are a major cause of infection-associated deaths and why early replacement of burned tissues is so critically important. There is an urgent need to engineer skin substitutes for patients with extensive burns who do not have enough skin available for harvesting as grafts to close wounds. However, relatively little is known about how to establish a large-scale production of skin substitutes and how to control the healing process when such material is used. Bone marrow-derived stem cells may be a potential source for the preparation of skin substitutes due to their capacity to be reprogrammed to produce a variety of cell types. Abelardo Medina is studying whether bone marrow-derived stem cells can be used in this fashion both to close wounds and to improve wound healing. Findings from his research may also lead to a better understanding of the healing process and the treatment of chronic non-healing ulcers that develop in elderly people, diabetic and immuno-compromised patients. It also may contribute to a better understanding of the processes associated with over-healing wounds such as those that result in thick burn scars.

Detecting, Treating and Preventing Drug-Related Morbidity

In Canada, 7.5 per cent of hospital admissions are complicated by an adverse event related to medical care that leads to death, disability, or a prolonged hospital stay. Adverse drug related events (ADREs) represent the most common cause of preventable non-surgical adverse events, with up to 130,000 patients in British Columbia (BC) presenting to Emergency Departments with a symptomatic ADRE. However, there are currently no efficient screening strategies for ADREs. This team is working to develop and evaluate a clinically effective, resource-efficient screening strategy. Once the strategy has been proven effective in an Emergency Department setting, the team aims to adapt it for use in community-based practice, and determine its cost effectiveness in comparison to the current standard of care.

PTEN Regulates Alternative Splicing

Prostate cancer is the most common non-skin cancer among Canadian men and the second leading cause of cancer death. Prostate cancer starts in the prostate gland, part of the male reproductive system. Frequently, men with early prostate cancer have no warning symptoms. PTEN is a tumour suppressor gene that has been linked to prostate cancer. PTEN helps promote apoptosis (cell death), which helps regulate the uncontrolled cell growth that occurs in cancer; unfortunately, PTEN is often mutated in advanced stages of prostate cancer. Alternative splicing is an integral part of normal cell function, and is important for generating protein diversity and controlling protein function. Tien Yin Yau’s study investigates whether PTEN plays a role in regulating alternative splicing. Yau is studying whether changes in normal mRNA splicing increase susceptibility to prostate cancer by affecting genes implicated in tumor progression. The findings of Yau’s study will increase our knowledge of the molecular mechanisms that regulate alternative splicing. Understanding what changes occur and their effects may result in the development of more effective cancer treatments.

Independence of identity and expression? A look at facial processing in both healthy and patient populations

Recognizing facial expressions and identities plays a crucial role in daily life. People who have experienced damage to identity recognition regions of the brain due to stroke, trauma or other causes are unable to recognize the identity of faces, often including their own. People with damage to regions involved in expression recognition have difficulty interpreting expressions, which leads to social mistakes. Problems in expression recognition may have a role in autism and other social developmental disorders. Studies have suggested that specific brain regions are primarily involved in either facial identity recognition or facial expression recognition. However, recent studies, including research Christopher Fox has contributed to, suggest the two are not restricted to independent regions. Fox is designing a series of psychophysical tests to determine the extent of the overlap and using functional magnetic resonance imaging to measure brain activity in both healthy individuals and those who have experienced brain damage. Fox aims to determine whether an area of the brain previously thought of solely as an expression recognition region is also able to process facial identity. The research could lead to new therapies for people with facial recognition disorders. Fox was funded as a 2005 trainee award recipient for research on the role of the temporal lobes in vision and the process of visual perception.

Mechanistic approaches to androgen-independent prostate cancer

Prostate cancer is the main form of cancer affecting men in the western world. Because cellular mutations within the prostate are regulated in part by androgens (male sex hormones), treatment of prostate cancer usually involves starving the prostate of androgens. While this therapy initially stops cancer progression, over time, the cancer continues to progress. Jennifer Locke is researching why prostate cancer progresses despite the apparent lack of androgens during treatment for the disease. Jennifer is testing the hypothesis that new androgens are produced within the prostate during androgen-deprivation therapy, causing the cancer to reoccur. Using molecular and analytical techniques, she is investigating androgen synthesis pathways. This research could enable identification and evaluation of inhibitors of these pathways, which may lead to new therapeutic options. Her ultimate goal is to improve treatment outcomes and quality of life for prostate cancer patients.

Identification of Mycobacterium tuberculosis virulence factors by pathogen effector protein screening in yeast (PEPSY)

Tuberculosis is a devastating disease that infects one-third of the world’s population, leading to eight million new cases and three million deaths per year. The prevalence of this disease is largely due to the ability of Mycobacterium tuberculosis (the bacteria that causes tuberculosis) to evade destruction by the immune system. Normally, when bacteria invade the body, the human response system triggers specialized cells called macrophages to engulf and destroy bacteria. In the case of tuberculosis, M. tuberculosis succeeds not only in escaping annihilation, but is able to enter and live inside the very cells that are programmed to destroy it. Using yeast as a model organism, Emily Thi is studying and identifying the components of the arsenal that Mycobacterium tuberculosis uses to successfully infect and survive within human macrophages. Her research on M. tuberculosis proteins that disrupt normal macrophage function may lead to the identification of novel targets for drug and vaccine development, which could result in new strategies to combat this challenging disease.

Cardiovascular morbidity and mortality associated with the use of corticosteroids in patients with rheumatoid arthritis: a population based study

More than 300,000 Canadians have rheumatoid arthritis (RA), a disease that causes chronic pain and inflammation in the joints. In British Columbia, more than half of people with rheumatoid arthritis receive corticosteroids to reduce inflammation. Several studies have shown that patients with RA are more likely to develop and die from cardiovascular disease (CVD) and, on average, live 12 years less than people without RA. The increased risk for CVD cannot be fully explained by traditional risk factors such as smoking, high blood pressure, diabetes, high cholesterol and a family history of CVD. Disease severity as well as treatment used in the management of the disease seems to play an important role in the development of CVD. Dr. Antonio Aviña-Zubieta is studying cases of individuals in BC who were diagnosed with RA between 1997 and 2000, and evaluating outcomes in people who received corticosteroids with those who did not to determine if there are differences between the two groups in the number of heart attacks, heart failure and stroke. This will help to establish if corticosteroids used in the treatment of rheumatoid arthritis contribute to CVD. He also will study whether the brand, dose and duration of use with different drugs influence the risk of heart disease. The results could offer new insights, leading to improved treatment and management of rheumatoid arthritis and other conditions for which these drugs are commonly prescribed.

Melanoma gene therapy by conditional replicative adenovirus targeting PUMA and p-Akt

Melanoma is a deadly form of skin cancer arising from the abnormal growth of pigment-producing cells in the skin. Melanoma is an aggressive tumour that spreads quickly to other parts of the body and is very difficult to treat because it does not respond to radiation or chemotherapy. In recent years, researchers have turned to gene therapy as a new approach to fight cancer. This approach is based on the idea that cancer is caused by defective genes. The goal is to eliminate the cancer by inserting therapeutic genes into cancer cells using a vector (a vehicle for delivering genetic material to a cell). Within melanoma cells, the expression (activation) of the cell death gene PUMA is often reduced and expression of the cell growth and survival gene Akt3 is often inappropriately increased. Using viral vectors known as CRAds, Alison Karst is focusing on reversing this pattern of gene expression in order to induce melanoma cell death. CRAD-based gene therapy holds promise for eliminating cancer cells and more effectively treating melanoma.