Atherosclerosis is a slow, progressive disease caused by the buildup of plaque (fatty substances, cholesterol, cellular waste products, calcium and other substances) in the inner lining of the arteries. This plaque buildup can lead to heart attack, stroke or gangrene. Research has shown that high-density lipoproteins (HDL) remove excess cholesterol from plaque by transporting cholesterol away from the arteries and back to the liver, thus slowing the buildup. Higher levels of HDL seem to be protective against coronary artery disease, and thus HDL is sometimes referred to as “”good”” cholesterol. Dr. Roshni Singaraja is researching the role of the newly-discovered gene ABCA1, whose function is to to produce HDL. Specifically, she is investigating the role of the palmitoylation process (the attachment of palmitate – fatty acids – to proteins which acts as a signal for the protein to be transported) on ABCA1 and its function. In addition, Roshni will examine the function of ABCA1 in the brain and the impact of palmitoylation on these functions. Roshniâs research may lead to potential strategies to increase HDL production and to accelerate or reverse cholesterol transport in order to prevent atherosclerosis.
Year: 2005
Biomechanics and prevention of vertebral fractures due to falls
Vertebral fractures in the spine are the most common type of fractures resulting from osteoporosis. These fractures cause back pain, impair physical function, reduce quality of life, increase mortality, and result in massive hospital and continuing care costs. After one vertebral fracture, the risk of a second vertebral fracture within 12 months increases fourfold. Most vertebral fractures result from a backwards fall. Dr. Meena Sran is conducting the first study to examine the forces that impact the spine during a typical backwards fall, and ways to reduce this load. Meena is investigating three promising techniques for preventing vertebral fractures during falls: having high risk fallers wear padded, shock-absorbing protective garments; installing floors that are less stiff; and using safe-landing techniques. The research could contribute new strategies to prevent vertebral fractures.
Characterization of the molecular phenotype of T regulatory cells
One of the major problems with organ transplantation is preventing the recipientâs immune system from rejecting the new organ. Currently, patients must follow a strict regime of immunosuppressive drugs for their entire life, which can seriously compromise their immune system and place them at significant risk. The development of a method to induce long-term drug-free acceptance of transplanted tissue and/or organs would have tremendous implications for both patients and the health care system. Research on a newly discovered class of cells called T regulatory cells (Tregs) is focused on finding a better solution to the problem of organ rejection. While researchers know that Tregs are capable of suppressing the activity of other T cells and that they play a significant role in regulating immune response, they do not have a clear understanding of the molecular mechanisms which trigger these actions. Natasha Crellin is studying the characteristics and molecular markers unique to Tregs, aiming to provide further understanding of the differentiation and function of these cells. The goal of her research is to better understand the potential for manipulating the bodyâs own immune response to replace use of immunosuppressive drugs in preventing organ rejection following transplantation.
Overcoming the barriers to axonal regeneration at the dorsal root entry zone in the acute and chronic setting
Traumatic injuries to the nervous system, such as spinal cord injury, can exert enormous physical, psychological, emotional and financial costs to the individual, their families and to society. A major physical consequence of spinal cord injury is sensory dysfunction (loss of normal sensory functions, including touch, pain, and temperature, and an inability to perform accurate motor tasks). All too often, this loss of sensory function is permanent, as spinal sensory nerves fail to regenerate after injury. There are many molecules within the nervous system that are capable of inhibiting the regeneration of nerve fibres. However, the exact mechanisms responsible for halting regrowth of sensory nerve fibres into the spinal cord after injury remain undefined. Dr. Lowell McPhailâs research objective is to identify and overcome the barriers to sensory fibre regeneration, following both acute and chronic dorsal root injury. Specifically, Dr. McPhail is examining injuries at the dorsal root entry zone (the point at which sensory axons enter the spinal cord), as it serves as an excellent system to model the environment of regenerating axons bridging the spinal cord injury site. Dr. McPhail is also investigating the mechanisms responsible for the ability of spared or uninjured sensory neurons to partially compensate for the lost sensory input following dorsal root injury. His research will attempt to identify potential therapeutic strategies for neurotrauma including, sensory nerve injuries, spinal cord injury and brain injuries.
Researching knowledge transfer and exchange in occupational and environmental health
There is growing recognition that many diseases and disorders, such as asthma, joint and tendon disorders, communicable diseases and some cancers can be caused, or aggravated by workplace exposures. Occupational health is one area where the translation of research findings into new policies and increased safety in the workplace can have an immediate and profound effect on work-related injury and disease. This process, known as knowledge transfer and exchange (KTE), involves the use of research knowledge in decision-making â for individuals setting workplace safety policy, managers supervising a workforce, or employees making decisions regarding risks in the workplace. While there is widespread recognition of the importance of communicating research knowledge to those who can benefit from it, there has been little research on the KTE process within occupational settings, and how this information can be effectively communicated outside academic circles. Research that focuses on KTE as a joint effort â where the expertise of both scientists and workers is considered and recognized â has yet to be examined within occupational settings. Dr. Anne-Marie Nicol is researching the process and context by which occupational and environmental research knowledge is exchanged from research scientists to policy-makers and to employees in the workplace. Her work includes analyzing the methods that occupational and environmental scientists use to promote their research knowledge, and examining what types of information the public and policy-makers use to make decisions about risk in the workplace. This research will help develop strategies to facilitate the effective exchange of research knowledge in a timely manner to people at risk from occupational and environmental exposures, and help ensure that the information people receive is useful and appropriate to their needs.
Pathways to aggression among high-risk girls: Disentangling genetic and environmental contributions
Rates of violence among adolescent girls in Canada and the US have increased over the last decade. As girls move into adulthood, aggressive behavior has been linked to a number of negative physical, social and psychological outcomes. High-risk girls account for rising costs in health care, juvenile justice and social service systems, but little research has focused on gender-specific responses to the problem of girlsâ aggression. Adult and male risk assessment models are used with girls, without evidence that these tools are applicable or effective. Dr. Candice Odgers is mapping girlsâ developmental trajectories across adolescence and early adulthood to identify the key risk and protective factors related to girlsâ aggression. In particular, Candice is examining the impact of maltreatment and victimization on predicting aggressive behavior among high-risk girls. She is also working with leading genetic scholars to investigate how these environmental risks interact with genetic risk to influence disruptive or aggressive behaviour. This research examines the interplay of nature and nurture in the development of aggression and should lead to more effective, and gender sensitive, screening and treatment procedures for girls.
Examining predictors of health behaviors across the life span
According to the World Health Organization, six out of the top seven risk factors for chronic illness are associated with a lack of physical activity, smoking and unhealthy eating habits. Adolescence is a critical period for establishing attitudes and behaviours associated with physical activity, eating, and tobacco use, yet little is known about the relationships among the health behaviours and the reasons for initiating or avoiding them. As a result, understanding and targeting adolescent behaviour can potentially have an important impact on health status across the lifespan. Catherine Sabiston is studying what influences adolescentsâ decisions to engage in healthy or unhealthy behaviours. She is reviewing several social, cultural and individual factorsâsuch as social support and relationships, gender-stereotypes, socioeconomic status, self-perceptions, competencies and valuesâthat affect physical activity, eating and tobacco use. Catherine is also interested in how these factors affect boys and girls differently, and whether these factors influence adolescents of a variety of ethnic backgrounds differently. This research should help explain the onset of and relationships among multiple health behaviours. Catherine will use this information to develop a school-based intervention program to target health behaviour change in adolescents, with the goal of developing realistic recommendations towards improving the long-term health status of Canadians.
Substrate spectrum of matrix metalloprotease-2 in physiology and pathology
Matrix metalloproteases (MMPs) are a family of extracellular proteases (enzymes) which reside outside cells and initiate the breakdown of proteins that mediate cellular signals. Processing by MMPs can activate, deactivate, or functionally convert signaling proteins. Within the MMP family, MMP-2 plays a pivotal role in cancer spread, since collagen IV degradation by MMP-2 allows tumor cells to penetrate the surrounding tissue. While MMP-2 is an attractive drug target for cancer treatment, clinical trials have shown that drugs which interfere with this enzyme cause severe side effects, partly because the protease is believed to play a part in so many other cell functions. Dr. Oliver Schilling is using innovative proteomic tools to identify and characterize novel MMP-2 substrates on a system-wide scale. His project aims to identify the abundant variety of natural substrates of MMP-2 as well as to the roles of MMP-2 and the cellular signaling pathways that the protease regulates. Given the prominent role of MMP-2 in tumor development, this knowledge has the potential to assist in the development of cancer drugs which are more effective and have fewer side effects.
Novel strategies for genetic modification and expansion of hematopoietic stem cells
Throughout life, blood cell production is dependent on a rare cell found in the bone marrow called the hematopoietic stem cell. This cell has the unique ability to divide and make identical copies of itself and also to generate progeny cells that can expand and acquire the specialized properties of mature circulating blood cells. Stem cells underpin a wide range of transplantation-based therapies for cancer, leukemia and genetic disorders. The use of these cells for therapeutic purposes requires genetic manipulation of hematopoietic stem cells, which involves inserting gene products directly into the cellâs genome. This procedure can also negatively affect chromosomes flanking the insertion site, causing variations in normal gene expression and malignant growth. Dr. Eric Yung is addressing these issues by developing methods to introduce new genes into stem cells without inserting them directly into the host genome. His strategy is to adapt and modify the ability of certain viruses to insert genetic material into cells. These methods may provide safer and more robust ways to achieve high level expression of genes. They may also aid understanding of the function of specific genes (for example genes that cause cancer) and the development of new methods to expand stem cells and develop new therapies for genetic disorders.
Developing a Chlamydia trachomatis vaccine by optimizing dendritic cell responses
Chlamydia trachomatis is the most commonly reported sexually transmitted infection (STI) in Canada. In BC alone, there were 7000 cases reported in 2003. Although antibiotic treatment is effective, more than half of all infections escape detection and timely treatment because they are asymptomatic in the early stages. Left untreated, the infection can lead to chronic pain and infertility. The development of an effective vaccine to prevent C. trachomatis infection is an urgent public health priority. No vaccine has been developed for C. trachomatis since an inactivated whole cell vaccine failed in trials in the 1960s. In order to better understand how the immune system responds to the bacteria and to develop candidate vaccine preparations, Dr. Michelle Zaharik is using cutting edge immunological and gene array technologies to probe how the immune system responds to C. trachomatis. She is looking particularly at dendritic cells (DCs) which play a role in activating the immune system to mount a defence against invading pathogens and are the subject of intense interest for vaccine development. Michelleâs study will identify the specific DC responses necessary to develop protective immunity against C. trachomatis. Ultimately, this may contribute to the development of vaccines specifically targeted to preventing chlamydial infections.