Cytochrome p450 2C Inhibition in Peri-transplant Ischemic Injury and Transplant Vascular Disease

Transplant vascular disease (TVD), characterized by a thickening of the arteries (arteriosclerosis), is the primary cause of chronic heart transplant rejection. TVD can be detected in up to 75 per cent of transplant recipients within only one year of transplantation. One factor that causes TVD is oxidative stress which occurs during the process of transplantation when blood flow is stopped in the donor heart prior to transplantation (ischemia), and then re-established in the recipient (reperfusion). This stress not only damages the heart but also makes it more susceptible to attack by the recipient’s immune system leading to chronic rejection. Previous research has suggested that an enzyme (CYP2C) is involved in triggering oxidative stress and heart damage during reperfusion. Arwen Hunter is investigating the process and mechanisms by which CYP2C causes cardiovascular damage. She will also investigate whether inhibition of CYP2C can suppress the amount of damage that occurs during transplantation and whether suppression of this damage can reduce chronic rejection later on. Results from these studies may lead to novel therapeutic strategies to alleviate chronic heart transplant rejection.

An adaptive intensity modulated radiation therapy (IMRT) technique through complete on-line treatment plan modification

Radiation therapy uses high energy, penetrating radiation to destroy or stop development of cancer cells, a process which also causes damage to surrounding healthy tissue. Conventional radiation treatment is created using a planning software that generates a plan based on the patient’s internal geometry (position of the target cancer cells and surrounding organs), and this plan remains unchanged for the whole treatment process. The ability to more closely and uniformly target the cancer cells, which includes the ability to map and adjust to changes in the internal geometry between and during treatments, would help to minimize impact to surrounding healthy tissue. A new form of radiation therapy known as adaptive radiation therapy (ART) may hold the answer. This modality allows for modifications of the original treatment plan before each treatment fraction, while the patient is in the treatment room. However, due to time constraints, only a selected set of treatment parameters of the original plan can be modified, which limits the full potential of this technique. Ante Mestrovic is exploring the development of a method for rapid, complete treatment plan modification that characterizes the patient’s internal geometry using three-dimensional ray tracing. His goal is to develop a time-efficient way of adapting treatment plans immediately before each treatment session. This would provide for more precise targeting of cancer cells, helping to reduce radiation exposure to healthy tissue and surrounding organs and contributing to a better outcome for patients undergoing radiation therapy.

An examination of injection drug use sites: the influence of social and physical context on drug-related harms and public health interventions

Injection drug use may result in severe health consequences including increased risk of viral infections such as HIV and hepatitis C, soft tissue infections, and drug overdose. Recently, with increasing attention being paid to the impact of environment on individual and public health, intervention efforts for injection drug users (IDUs) have moved beyond the modification of individual behaviour and focused on modifying the environments in which people use injection drugs. One recent and controversial example of this involves medically supervised injection facilities, where IDUs can inject pre-obtained illicit drugs under the supervision of health care professionals. William Small is studying and comparing three types of injecting settings in the Downtown Eastside: private injecting spaces (such as homes), public injecting spaces (such as alleys), and Vancouver’s supervised injecting facility. He is examining how the social and physical context of each setting influences the ability of injection drug users to employ HIV-prevention measures and safer injection practices. The findings of this research will build important knowledge about the health and HIV vulnerabilities of IDUs in the Downtown Eastside. Also, this research will provide information on the impact of current interventions, which may inform future interventions for addressing injection drug use.

Molecular basis of tenascin elasticity and mechanotransduction

Tenascin is an important family of proteins found in the extracellular matrix of tissues—the filamentous structure that is attached to the outer cell surface and provides anchorage, traction, and positional recognition to the cell, and plays important roles in regulating the interactions between cells and the extracellular matrix. It is also known that tenascin mutations are linked to disorders that affect the mechanical properties of skin tissues and joints. However, little is known about the mechanical properties of tenascins and how they are regulated to adapt tissues to withstand force. To study tenascin, Dr. Hongbin Li is stretching single molecules of the protein and examining its mechanical response. He will also evaluate the consequences of disease-causing mutations on the mechanical behaviour of tenascins. These studies will provide new insight into the molecular basis of tenascin mechanics, and help to pinpoint the cause of tenascin-related connective disorders. They may also offer useful information in developing tissue engineering strategies for skeletal repair.

Rostrolateral prefrontal cortex modulation using real-time fMRI feedback training in healthy volunteers and depressed patients

Depression is a common mental disorder characterized by sadness, low energy, feelings of guilt and low self-worth. Even after patients recover from a major episode of depression, they remain vulnerable to subsequent depression relapse. Such depression relapse can be triggered by a relatively mild experience of sadness, during which depression vulnerability expresses itself through reduced metacognitive awareness: the awareness of one’s own thought processes. Neuroimaging studies suggest that increased activation within the brain’s lateral prefrontal cortex—the same region linked to metacognitive awareness—is a positive result of treatment for depression, and that consistent activation may reduce the risk of depressive relapse. Dr. Kalina Christoff is researching whether patients who are prone to depression can prevent relapse by learning how to better control their brain activity within this region. She is examining whether real-time feedback from functional magnetic resonance imaging (fMRI) can help patients learn to consciously modulate their brain activity and prevent or reduce relapse.

The role of Prostate cancer support groups (PCSGs) in health promotion

There is a significant body of research that describes the psychosocial, rehabilitation and health needs of men diagnosed with prostate cancer. These needs cannot always be met by professional health care services, particularly in the case of health promotion programs intended to help men with prostate cancer maintain and optimize their health and well being. While more and more men are accessing community-based support services such as Prostate Cancer Support Groups, little is known about whom these groups serve, what services they offer, and how they are funded.

Dr. John Oliffe is exploring the role of Prostate Cancer Support Groups in health promotion, and determining how men’s health and illness behaviours are informed and influenced through attending these support groups. Through a better understanding of how these groups operate, he hopes to develop recommendations about how best to support this type of resource, and identify potential ways to integrate the groups with professional health care services. This work will help inform future content, design and implementation of prostate cancer health promotion programs.

Oncology Nutrition

This award supports the creation of a team focused on advancing research in a new and emerging field: oncology nutrition. Through conferences, educational sessions and workshops, the team aims to achieve key goals that include: identifying research priorities and resources; identifying partners for individual and multi-centre projects; and gaining consensus on research design and methodology. Other goals include mentoring cancer care staff and developing a database within cancer treatment centres for future research.

The effect of a province wide, school-based physical activity initiative on the behavioral symptoms of Attention-Deficit Hyperactivity Disorder (ADHD) in children

Attention-Deficit Hyperactivity Disorder (ADHD) is one of the most frequently diagnosed psychiatric disorders of childhood. Children with ADHD have a high rate of disciplinary problems in school, experience social and academic difficulties, and encompass 30 to 40 per cent of referrals to child guidance clinics. Given the frequent occurrence of ADHD and the issues associated with it, effective and appropriate treatment has become a critical issue. With the desire to provide a healthy and effective solution in treating the symptoms of ADHD, Nicole Smith’s study is exploring the effects that repeated physical activity may have on the symptoms of ADHD in a practical setting. Using a standardized ADHD questionnaire, parents and teachers will indicate the degree of influence a long-term, province-wide, school-based physical activity initiative has on the behavioural symptoms of children with ADHD while in their classroom and home environments. The primary goal of Nicole’s research is to evaluate the effect of school-based physical activity intervention on ADHD symptoms and classroom disruption among children ages 9 to 12 with ADHD. Since little research exists on the impact of exercise on the behavioural symptoms of ADHD in children, there is potential for this research to make a significant contribution in the areas of child mental health, ADHD health promotion and intervention.

Genetic Factors in Premature Ovarian Failure

Although the average age of menopause is 51 years, approximately one per cent of women will experience menopause before the age of 40, a condition known as premature ovarian failure. Working on the hypothesis that multiple genetic factors may combine and interact in a single individual to determine the rate of reproductive aging, Karla Bretherick is examining the molecular genetic differences between women with normal reproductive function and women with premature ovarian failure. She hopes her work identifying specific genetic factors that contribute to early menopause may lead to the development of both treatment options for affected individuals and predictive testing for those at risk.

Role of Myosin Va in trafficking of neuronal vesicles

Neurons (brain cells) are separated by gaps called synapses and communicate via mechanisms which enable them to send and receive signals across these gaps. Inadequate development and maintenance of synapses is associated with a number of neurological and psychiatric conditions, from epilepsy to anxiety disorders, autism and mental retardation. Neurons use axons and dendrites to communicate across synapses. Axons are long fibers that transmit impulses to other neurons. Dendrites form a network of branches that receive signals from other nerve cells. Newly-made proteins within neurons must be transported to appropriate sites in axons or dendrites for proper communication to occur. However, little is known about how these proteins are accurately relocated. Frederick Dobie is studying one of the molecules thought to be involved in protein transport (Myosin Va), which is widespread in the brain, to clarify its role in pre and post-synaptic communication. Research has shown that a mutation in Myosin Va leads to Griscelli Syndrome, a disorder which causes severe motor and neurological impairment in humans. Other CNS disorders may also result from malfunctions in intracellular transportation of the proteins that facilitate communication between neurons. A better understanding of the action of transport molecules may lead to better methods of treatment for neurological disorders.