Year: 2009

Role of beta-cell Toll-like receptor signalling in type 2 diabetes

Diabetes mellitus is a chronic disease that affects over 180 million people worldwide. At least two million Canadians currently live with the condition, a figure expected to double in the next 10 years. Type 2 diabetes accounts for 90 percent of cases and has been recognized by the World Health Organization as a global epidemic. Thus, urgent action is needed to reduce the economic and social burden of the disease and its complications. Diabetes is characterized by insufficient production of insulin, a hormone released by the pancreas that regulates blood glucose levels. Type 1 diabetes is an autoimmune disease caused by destruction of insulin-producing beta-cells within the pancreatic islets. Type 2 diabetes is characterized both by resistance to insulin action and by impaired beta-cell insulin production. Inflammation, an immune response to tissue damage, is important in both conditions. Islets from patients with Type 2 diabetes exhibit increased levels of pro-inflammatory cells and proteins. These contribute to beta-cell damage and impaired insulin production, representing a potential target for therapeutic intervention. High circulating levels of glucose and fatty acids, in addition to toxic deposits of a small protein called islet amyloid polypeptide (IAPP), may signal via pattern recognition receptors on cells within the islet to promote an inflammatory state. However, a better understanding of the causes of islet inflammation is required for effective development of targeted therapies. Clara Westwell-Roper’s research focuses on the role of pattern recognition receptor signalling in islet inflammation induced by metabolic stimuli and IAPP. Her research will enhance our knowledge of the mechanisms that contribute to beta-cell death and impaired insulin secretion in patients with Type 2 diabetes. An understanding of the causes of islet inflammation may facilitate the development of new medications that improve pancreatic islet function.

An Examination of the Risks and Health Needs of Adolescents and Young Adults with FASD in the Criminal Justice System.

Fetal alcohol spectrum disorder (FASD) is an umbrella term referring to a range of permanent deficits that occur in a developing fetus as a result of exposure to alcohol during pregnancy. FASD is the leading cause of developmental disability among Canadian children and is identified as a major public health concern in Canada. Individuals with FASD experience high rates of health related problems, including serious mental illness and substance use, homelessness, violence and victimization. In BC, the government has committed to the important goal of providing individuals living with FASD the support needed to reach their full potential in healthy and safe communities. To assist in achieving this goal, the province has called for more research to inform treatment efforts in general health and justice settings. Kaitlyn McLachlan’s research speaks to that need by providing a knowledge base specific to the risks and health needs of youth diagnosed with FASD in the justice system. The overall purpose of this study is to improve health outcomes for justice-involved youth with FASD, in part, by developing a knowledge-base about offending patterns and salient risk indicators in youth with FASD. The project will be based in BC and parallel data collection efforts will be made in additional provinces so that reliable conclusions can be made about this population. The information from this study can be used to inform the targets and timing of interventions and improve clinicians’ recommendations about risk, risk management and interventions. The knowledge gathered about mental health and substance use problems will also be crucial in determining the types of community-based services youth with FASD require outside the justice system in order to maintain good health.

Development of Clinical Standards of Care for Huntington disease Intermediate Allele Predictive Test Results

Predictive testing for Huntington disease (HD) has been available since 1986. This genetic test has the ability to ‘predict’ whether individuals will develop HD in their lifetime and possibly pass the disease onto their children. Some individuals who undergo predictive testing receive an unusual test result, called an ‘intermediate allele’ (IA), which differs from a gene positive or negative result. While individuals with an IA will never develop HD themselves, there remains a risk that their children or grandchildren could subsequently develop the disorder. Currently, knowledge gaps exist with respect to IA for HD. Specifically, the current International Predictive Testing Guidelines do not address the possibility of this result, nor are the complexities surrounding this result acknowledged in the literature. Alicia Semaka’s research, which is the largest empirical study on HD IAs to date, will not only address these gaps, but also inform the development of clinical standards of care for communicating IA results during predictive testing. The specific objectives of Ms. Semaka’s research are to determine the prevalence of IAs in British Columbia’s general population; determine quantified risk estimates for the likelihood that an individual with an IA will have a child who will develop the disease in their lifetime; and lastly, describe the psychological and social impact of receiving an IA result. Collectively, the three objectives of this unique, multidisciplinary study will provide the foundation for the development of clinical standards and practice recommendations for IA predictive test results. These standards will help ensure that this subset of patients receive appropriate information, support, education and counselling throughout the predictive testing process.

Identifying clinically relevant biomarkers in lymphoma using next-generation sequencing

Lymphomas are a class of cancers that generally derive from blood cells known as B-cells that are present within organs called lymph nodes. Similar to other cancers, lymphoma tumours can be surgically removed. However, patients often relapse after surgery because, inevitably, a small number of cancer cells remain in the body. Diffuse large B-cell lymphoma (DLBCL), is one of the most common types of lymphoma. Sophisticated techniques that allow one to view the abundance of genes (expression,) or the genetic code (DNA sequence), of cancer cells can reveal clinically relevant distinctions between cases of DLBCL. This type of grouping is important because, for example, patients with one subgroup of lymphoma known as the ABC variety appear to have an inferior response to current standard therapies compared to those with the more common GCB variety of DLBCL. The signals that define distinct subtypes of cancers are often referred to as biomarkers and their presence or absence can, in some cases, be tested in a clinical setting. Ryan Morin is focusing his research on the identification of new biomarkers in cancer cells from a clinically diverse group of lymphoma patients. Additionally, Mr. Morin’s research will focus on the identification of genes that have been damaged by somatic mutations, and thereby the identification of genes important to the development of DLBCL. By cataloguing the identified cancer driver mutations, it may be possible to use their signatures to define new subgroups of lymphoma with distinct characteristics. Marrying this information to new biomarkers may help determine whether any new biomarker is associated with positive (i.e. cure), or negative (i.e. relapse), clinical outcomes. Finally, the identification of biomarkers and specifically somatic mutations altering protein function may reveal possible vulnerabilities of a cancer cell to specific drugs. For example, a mutation that results in activation of an oncoprotein may allow a clinician to choose an appropriate drug that inhibits that protein. Further, if no drugs are available, these findings may spur the development of new drugs to specifically target the mutated or activated proteins responsible for malignancy.