More than 2 million Canadians and 135 million people worldwide have diabetes, a chronic medical condition characterized by a lack of insulin (Type 1), or insensitivity to insulin (Type 2), a blood sugar-lowering hormone. Type 1 diabetes can be treated by transplantation of islets, which contain the insulin-producing cells, to patients, but use of this therapy is limited by the huge volume of islets required to treat all Type 1 diabetes patients. As a result, most continue to rely on insulin injections to help control blood glucose levels. Glucagon-like peptide-1 (GLP-1) is produced in the intestine and has numerous anti-diabetic effects. Clinical trials are currently investigating GLP-1 as a treatment for Type 2 diabetes. Other recent studies show GLP-1 also enhances the growth of islet tissue. As a 2003 MSFHR Trainee, Rhonda Wideman investigated the effects of GLP-1 on the growth and survival of transplanted islets to determine if GLP-1 reduces the amount of islets needed to treat Type 1 diabetes in transplant recipients. Now in a PhD program, Rhonda is examining the therapeutic potential of engineering islets to produce GLP-1. She is investigating whether islets in which GLP-1 production has been induced will indeed survive and function better following transplantation. This would reduce the amount of islets necessary for a successful transplant and enhance post-transplant islet function. Ultimately, Rhonda hopes her studies will contribute to improved islet transplantation protocols, which are more effective and less reliant on limited supplies of donor islet tissue.
Year: 2005
Molecular characterization of a phosducin-like protein and its co-operation with the protein folding machine CCT
Each year millions of people worldwide are diagnosed with diseases related to disordered protein folding. Normally, protein chains fold into a defined shape in order to function properly and when this process is disrupted, diseases such as Huntington’s, Alzheimer’s, cystic fibrosis and some forms of diabetes occur. The regulators of protein folding are called molecular chaperones, and as the name implies they have an important, but not well understood, assistive role in the process. Many molecular chaperones are essential for a cell’s survival. Some chaperones have been directly linked to the causes of genetic disorders involving misfolded proteins but others have been shown to be involved in slowing and preventing neurological diseases like Alzheimer’s. Peter Stirling’s research focuses on a protein called phosducin-like protein 3 (PhLP3), shown to be involved in facilitating protein folding as it interacts with an essential chaperone called CCT. Peter aims to understand how PhLP3 affects protein folding and what functional consequences the PhLP3-CCT interaction has. Peter’s research will help answer fundamental questions about how cells efficiently generate and maintain properly folded proteins, which will ultimately help to better understand what is happening in a cell when protein folding is disordered. His results may eventually lead to better treatment for diseases associated with protein misfolding.
Novel photoactive biomolecules: A photosensitive purine based drug release strategy and new methodology for generating PET labeled biomolecules
Medical imaging techniques such as X-rays, CT scans and MRIs, are widely used tools for diagnosing injury and illness. These tools provide a “”picture”” of bones, organs, muscles, tendons, nerves and cartilage, including any abnormalities. A new and evolving imaging technique called positron emission tomography, or PET scanning, provides additional details by creating a three dimensional image or map of functional processes in the body. By injecting radiolabelled molecules into the bloodstream, and then tracing their path and interactions, researchers and doctors can observe and map metabolic activity within various organs of the body. Photodynamic therapy (PDT) which is used in the treatment of psoriasis and certain cancers is similar to PET scanning in that photodynamic molecules (photosensitizers) are injected into the bloodstream. When the tissue to be treated is exposed to special light, the photosensitizers are activated, leading to a destructive action which kills abnormal cells. Richard Ting’s research is focused on examining and developing novel molecules, with potential application for both PET scanning techniques and photodynamic therapy. He aims to design a new class of molecules that would expand the limited amount of agents that can be imaged during PET scanning. In addition, he is researching a new class of molecules that could be used to improve the processes involved in photodynamic therapy.
Aboriginal women and children's access to health care services in rural and remote BC
Aboriginal people in Canada, like indigenous people around the world, continue to experience persistently lower health status than other populations. Although researchers are tracking these health outcomes, there is a lack of enough detailed information about the specific processes that prevent Aboriginal people from meeting their health needs, and how the health service delivery system facilitates or hinders meeting those needs. This is an especially important question for children in view of the significance of the early years for future health. Silvia Vilches is working directly with parents, primarily women, within an aboriginal on-reserve community, to explore what parents and caregivers see as priorities and opportunities for enhanced health and well-being in their communities. Her work will take into account the interactions between federal health care funding and provincial health care systems, the continuing impact of colonization on aboriginal communities, and the desire for aboriginal communities to determine and express their own needs. Research has shown that Aboriginal people want culturally appropriate, holistic community health services. This type of project-based investigation could lead to better models of health service delivery planning for rural and marginalized populations that matches community priorities.
Herbal medicine use and older adults: A social network analysis of information exchange
National surveys indicate that seniors account for a growing number of new herbal users, with the majority reporting use of at least one herbal within the last year. A growing number of older adults are seeking treatments outside of conventional medicine, and in many cases, are not informing their primary physician of this use. Lack of communication with medical doctors, coupled with the fact that information sources about herbal medicines are not always credible, creates the potential for drug-herb interactions, poor or delayed treatment and misconceptions about the efficacy of herbals for health. Doctors tend not to refer their patients to herbal practitioners or prescribe herbal medicines. Consequently, seniors rely on other sources to get this information. Kristine Votova is investigating how older adults obtain information about herbal medicines from their social networks. Kristine is assessing how these connections influence a senior’s decision to use herbal medicines. For example, are seniors more likely to act on information from people they have strong or weak ties with? And what impact does the age, sex and health status of those providing information have on the prevalence, frequency and duration of herbal use? This research will explain how seniors exchange information about alternative treatments, and can be used to target public health messages about the safety of these products.
Vascular endothelial growth factor induces endothelial cell hyperpermeability to low density lipoproteins in atherosclerotic disease
Coronary artery disease (CAD) and transplant associated-CAD are caused by a reduction or complete blockage of blood flow in blood vessels of the heart, which results in tissue death due to lack of oxygen. CAD is the leading cause of heart attacks, and transplant associated-CAD is the leading cause of organ failure one year after transplantation. Both diseases are characterized by abnormalities in blood vessel walls – abnormalities that result in the accumulaton of lipids and other blood components inside vessel walls. This causes them to thicken which acts to constrict blood flow. The endothelium is a blood vessel lining that serves as a barrier between the blood and tissue and also has a role in directing the transport of ions, lipids and proteins. Previous research has shown that vascular endothelial growth factor (VEGF), one of the most potent inducers of vascular permeability, is upregulated in these diseases. Brian Wong is working to determine the specific mechanisms by which VEGF induces this effect. He hypothesizes that the abnormal production of VEGF in CAD and transplant associated-CAD compromises endothelial barrier function, resulting in the increased passage of lipids and proteins into the vessel wall. Ultimately, he hopes to determine the therapeutic potential of blocking VEGF production in order to reduce lipid entry and accumulation in the vessel wall and prevent these diseases.
Biochemical and structural characterization of bacterial type III secretion system components
Harmful bacteria are becoming much more resistant to the currently available antibiotics, a situation that poses a serious threat to public health. The development of new and more effective ways of protecting against these increasingly dangerous (and antibiotic resistant) microbes requires a thorough understanding of the molecular mechanisms through which they cause disease. The bacterial type III secretion system (TTSS) is a complex mechanism that controls how bacterial proteins are transfered into human cells, a process that is essential to the disease-causing capabilities of a large number of pathogens, including Salmonella and pathogenic E.coli. Although many components of the TTSS have been identified, exactly how this secretion system is assembled and how virulence proteins (toxins) are delivered into target cells remains poorly understood. With support from a 2002 MSFHR Trainee Award, Calvin Yip successfully described the first high resolution structure of an extracellular component of the TTSS. Now funded for a second time, he is working to further characterize its structure and function. This work will help answer fundamental questions about the biochemical and structural characterization of TTSS, and may facilitate the design of new classes of drugs to combat a broad range of infectious agents.
Social effects on a linguistic mechanism in Autism Spectrum Disorders
Children and adults with one of the group of pervasive developmental disorders known as Autism Spectrum Disorders (ASD) have difficulties with language and social interaction. Language problems are especially disabling, as most activities rely on language. Katherine Yoshida is researching whether the ability to learn language is impaired in people with ASD because it is generally learned through social cues and interaction. Children, for example, may follow a parent’s eye movement to associate a word with an object. But children with ASD often do not make eye contact. Katherine is investigating whether reliance on social interaction to develop language impedes learning in people with ASD. The research could confirm that people with ASD learn language more effectively in non-social settings, and the results could be used to develop alternative learning strategies that improve communication abilities in people with ASD.
Functional analysis of interferon inducible protein 10 gene in Coxsackievirus B3-induced myocarditis
Coxsackievirus B3 (CVB3) is the leading cause of viral myocarditis, an inflammation that can so severely damage the heart that a heart transplant becomes the only treatment option. Previous studies have identified 28 up – or down – regulated genes in CVB3-infected mouse hearts, but the functions and mechanisms of the host gene regulation in the progression of CVB3-induced myocarditis are not clear. Ji Yuan is further analyzing the role of host gene alteration in viral myocarditis by investigating the IP10 gene, believed to be the most crucial up-regulated gene. Her objective is to define the functional role of IP10 and trace the cascade of events precipitated by its up-regulation which result in major damage to the heart. By conducting these experiments, she will not only have a better understanding of the molecular mechanisms of viral myocarditis, but also may discover potential targets for gene therapy or new diagnostic tests for this heart disease.
Treatment readiness and motivation research: improving quality of care and health outcomes
Treatment refusal, dropout, and relapse are common in individuals with eating disorders, resulting in physical and emotional costs to the patient, societal costs to the community, and economic costs to the health care system. Dr. Josie Geller’s previous research has shown that a patient’s readiness to change is the best predictor of clinical outcomes in the eating disorders. However, there remains a need for validated assessment tools and guidelines to determine which patients are ready for what type of treatment; development and evaluation of interventions that enhance readiness for treatment; and dissemination of findings from this research to clinicians and to community support providers on the benefits of matching treatment to patient readiness. The primary objective of Dr. Geller’s research is to use a patient-focused approach that draws upon applications of psychological models of readiness and motivation for change to improve health service delivery, utilization, and quality of care. Her program aims to provide a set of guiding principles for efficient, cost-effective care that has broad applications to the health care system, including eating disorders, HIV, Hepatitis C, and other emerging priority areas.