Gold Nanoparticle-Conjugated Antibodies as Optical Contrast Agents for In Vivo Molecular Imaging of Cancer

Cancer is the leading cause of premature death in Canada, and the number of new cases continues to rise as the population grows and ages. Based on current rates, 38 per cent of Canadian women and 44 per cent of Canadian men will develop cancer in their lifetimes, many when they are 70 or older. Traditionally, physicians assess the severity of cancer tumours by removing tissue samples from a patient and assigning a severity score based on what they see under the microscope. This process can be time-consuming and yields limited information. Recent discoveries have identified a number of molecules produced by cancer cells. Gerald Li is working on an optical imaging system to detect and evaluate the presence of these molecules. In particular, his focus will be on the use of specially designed probes that will flag these molecules, allowing a physician to immediately identify malignant cells. This system will make it possible to image various parts of the body to detect cancer earlier, predict which pre-cancerous lesions will become tumours, and image tumours in the operating room to help determine the boundary between healthy and malignant cells. It will also assist in the selection of treatments targeting cells that create these molecules.

Who has Epilepsy in British Columbia?

According to national surveys, an estimated 30 per cent of Canadian children between six and 18 years of age suffer from chronic conditions and/or disabilities, including seizure disorders. However, these surveys do not allow for provincial analysis, due to small sample sizes, and there is limited comparability between surveys because of differences in target groups, methodologies and conceptual frameworks. Currently, there are no comprehensive prevalence data on children with special health care needs in BC, such as children with epileptic seizures, who account for half the visits to specialists because of neurological disease. Veronica Schiariti is researching the influences of neighbourhood income, population density, health care availability and community resources on the treatment prevalence of epilepsy in BC children under the age of 19. She is examining both diagnosis and treatment patterns of pediatric patients with epilepsy. Veronica hopes that her research will contribute to improved treatment for epileptic children by identifying disparities in health service delivery, informing health care policy decisions, and enabling long-term tracking and study of health and development outcomes at the individual level and in the broader population.

The role of CD72/CD100 interactions in NK cell activation

Resistance to cancer and infectious diseases relies on complex responses in our immune system. Natural killer (NK) cells provide a first line of defence, recognizing and killing infected and tumour cells, while sparing normal cells. NK cells use an intricate system of proteins, found on their surface, to either activate or inhibit their “natural killer” activity. However, the mechanisms by which these proteins induce this action are not completely understood. Dr. Valeria Alcón is studying two cellular proteins (CD72 and CD100) that are involved in the activation of several immune cells to determine how these proteins regulate natural killer cell activity. She is also examining how NK cells interact with other immune system cells to induce immune responses. Her research could explain how to activate natural killer cells, leading to the development of more effective treatments for infectious disease and cancer.

Mathematical modelling of axonal sprouting signalling

One of the major challenges of neuroscience is the lack of regeneration of the mammalian central nervous system when it is injured. Extensive effort has been devoted to promote growth of regenerating axons (fibres that sent impulses from one neuron to another) across the lesion site. Since 55 per cent of spinal cord injuries are incomplete, in many cases a portion of axonal connections between brain neurons remain intact. These intact connections can be induced to form collateral branches, or sprouts, that cross the spinal cord midline and stimulate the other side, leading to some locomotion recovery. Finding ways to enhance this sprouting is a promising strategy to improve recovery in patients with incomplete spinal cord injuries. Ana Le Meur is using mathematical modelling to complement experiments to gain knowledge about the mechanisms regulating sprouting of neuronal connections. By generating a comprehensive model of collateral sprouting, this research will take an important step toward enhancing recovery after spinal cord injury.

Tissue Specific Functions of ABCA1

An individual’s cholesterol levels – both LDL (or “bad” cholesterol) and HDL (or “good” cholesterol) – are known to be a significant predictor of the risk for heart disease. While much attention has been focused on lowering levels of LDL, much less is known about the factors that determine HDL levels and how to alter these levels. However, research suggests that every 1 per cent increase in HDL levels results in an approximately 2-3 per cent decrease in risk for cardiovascular disease. With insight into how to raise HDL levels, a majority of the population might avoid developing heart disease. The gene ABCA1 has been identified as crucial to the production of HDL cholesterol, and is expressed in many tissues in the body. However, it is unclear which specific cell types or organs are responsible for the generation of HDL particles. Liam Brunham is investigating the specific role of ABCA1 in different tissues of the body and determining how ABCA1 in these tissues responds to different genetic and dietary environments. This research will increase the understanding of how ABCA1 functions to determine HDL levels, and suggest new ways to protect against heart disease.

Socio-ecological analysis of HIV/AIDS treatment-related behaviours and health outcomes in an era of HAART: Considering individuals in the context of their communities

“Highly active antiretroviral therapy” (HAART) has led to dramatic improvements in quality of life and survival for people infected with HIV/AIDS. But these positive outcomes are not evenly distributed among HIV-infected individuals. Despite access to free medications in Canada’s publicly funded health care system, vulnerable groups such as HIV-positive women, injection drug users and socio-economically disadvantaged people have not experienced the health improvements others have. Research to date has focused largely on individual risk factors. Angela Kaida is examining how individual and community factors, such as neighbourhood income levels and the availability of HIV/AIDS services, affects the quality of treatment and health outcomes of people infected with HIV. Angela is assessing the role these factors play in delaying entry into treatment, non-adherence to treatment, and the advance of HIV/AIDS disease and death. In earlier research, Angela studied the impact of HIV/AIDS on agricultural production, food security and rural livelihoods in Malawi, and on male involvement in family planning in Uganda. The findings from her current study have the potential for application in the design of community programs and policies to improve equal access to HAART in Canada, and may be applied in global settings with high HIV prevalence.

Characterizing the role of sumoylation at the budding yeast kinetochore

Aneuploidy – the result of the uneven separation of two matching sets of chromosomes during cell division – is found in more than 70 per cent of cancers and is now widely accepted as a major predisposing condition to cancer initiation and progression. Benjamen Montpetit is studying the role of the kinetochore, a protein complex that is of fundamental importance to the equal separation of chromosomes during cell division. Using yeast cells as a model, his research into the components responsible for chromosome transmission will result in a better understanding of the events involved in creating aneuploid cells and will provide a mechanistic basis for understanding chromsome instability in human cancers.

Pharmacogenetics of Mycophenolate in Thoracic Transplant Recipients: Role of UDP-Glucuronosyltransferase Genetic Polymorphisms

Thoracic (heart and/or lung) transplantation is an effective but aggressive measure for treatment of end-stage heart and lung diseases. However, rejection of the transplanted organ remains a major problem and frequently leads to organ loss and death. All transplant recipients take immunosuppressants (drugs that prevent rejection), yet over-immunosuppression exposes them to undesirable infections and other side effects. Mycophenolic acid (MPA) is an effective immunosuppressant commonly used in transplantation. However, tailoring MPA therapy is challenging due to the wide variability and unpredictability in treatment responsiveness and side effects among patients. Genetic makeup and metabolism of MPA have a significant bearing on drug responsiveness. While many studies provide better understanding of MPA in kidney transplant recipients, information on the thoracic transplant population is scarce. Lillian Ting’s research is exploring the role of genetics in determining treatment responses. The ultimate goal is to individualize regimens, even before treatment begins, for each patient in order to obtain optimal treatment response and minimal toxicity. The results from Lillian’s study will add valuable knowledge to transplantation management. It will be directly incorporated into patient care, improving patient survival and quality of life after transplantation.

Endoplasmic reticulum-plasma membrane contact sites: Regulation of ER structure and cell growth

Lipids play important roles in all cells, separating the cell from the outside environment and serving to divide the cell into distinct compartments called organelles. In order to carry out their critical biological processes, organelles need to contact and communicate with each other. The disruption of these contacts can result in defective movement of lipids, and the accumulation of lipids is a factor in diseases such as atherosclerosis, Alzheimer’s disease, type 2 diabetes and motorneuron diseases. The endoplasmic reticulum is an organelle that is made up of a network of membranes within cells, involved in the synthesis, modification, and transport of cellular materials. Communication of the endoplasmic reticulum with other organelles is especially important to the cell, because it is the site of many metabolic activities, including making lipids and proteins. Dr. Christopher Loewen is working to determine how the endoplasmic reticulum contacts and communicates with other cell compartments, particularly with regards to lipid synthesis. By studying these contacts, he hopes to shed light on both normal and dysfunctional communication, potentially uncovering new ways to fight lipid accumulation.

Neuromagnetic responses related to the development of orthographic perception

As normal hearing and sighted children learn to read, they gain knowledge of associations between letters or words and their related sounds. Particular brain regions and processes are implicated in reading—reflected by measurable changes in brain activity—which develop as children progressively gain reading ability. By recording the magnetic fields produced by the brain, Dr. Anthony Herdman is identifying the changes that occur in brain activities when children begin to recognize letters. He is also investigating what happens in children’s brains when they combine sight and sound in order to learn letter-sound and word-sound pairs. His goal is to gain a better understanding of the changes in cerebral activity within in the developing brain over the course reading acquisition.