With drug addiction, people typically resume seeking drugs if exposed to cues associated with the drug. This phenomenon, called cue-induced reinstatement, is frequently studied, but a number of neurological issues have yet to be addressed. Two parts of the brain may be a common link in the neural circuitry underlying these cue-induced responses. These are the amygdala, the portion of the brain that regulates emotions, and the prefrontal cortex, a part of the frontal lobe involved in executive functioning. The two areas respond differently to cues for food rewards than to drug cues. Ryan McLaughlin is investigating the similarities and differences in how these areas of the brain regulate food and drug rewards to determine if the difference results from long-term alterations in brain function, brought about by repeated drug use. If so, this research will confirm that chronic drug abuse can radically alter how the brain processes information and could eventually lead to new treatments for people trying to recover from drug addiction.
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Relations among maternal sensitivity in early infancy and infants' attachment security at 12 months
The quality of the mother-infant relationship early in infancy forms a foundation for infants’ subsequent social and emotional development. In particular, mothers’ sensitive responses to behavioural cues helps their infants develop a sense of self and other and helps them regulate their emotions. Attachment—or the bond between infants and their caregivers—is a developmental achievement in the first year of life that is essential for healthy physical and psychological growth. Studies have shown that insecurely-attached infants are at risk for a range of negative developmental outcomes. Nancy Mcquaid is working to identify ways in which mothers interact with their infants that facilitate, or inhibit healthy social and emotional development. Nancy’s research will contribute to our understanding of healthy infant development and will help develop means of intervention for infants who are at risk for developmental emotional and interactive disturbances, such as infants of mothers with postpartum depression and low birth weight infants.
Evaluating Patients’ Preferences for Asthma Therapy Using a Discrete Choice Experiment
Approximately one in 12 Canadians has asthma, a chronic respiratory disease characterized by airway inflammation and variable airflow obstruction. Previous research into how asthma patients manage their disease has found an over-reliance on short-acting beta-agonists (used as needed to quickly relieve symptoms) and an under-use of inhaled corticosteroids (used regularly to prevent asthma attacks). This treatment pattern has been associated with a higher risk of death related to asthma. The overuse of short-acting beta-agonists appears to be linked to socioeconomic status. Despite receiving all drugs at no cost, asthma patients receiving social assistance are more likely to use greater amounts of short-acting beta-agonists than individuals not needing assistance. Helen McTaggart-Cowan is conducting research aimed at identifying the extent to which patients are willing to trade off the immediate symptom relief of short-acting beta-agonists against the ongoing management achieved with inhaled corticosteroids. She is investigating the relative importance of symptom control, cost, side effect minimization and convenience of treatment in an effort to determine the associations between drug preferences and both socioeconomic status and asthma control status. By identifying the factors that result in inappropriate asthma management, Helen’s research will contribute to improved asthma care and provide a foundation for future work aimed at improving treatment efficacy and compliance.
Measurement and training of fall-protective responses
Hip fractures represent a significant health problem for the elderly. While 90 per cent of hip fractures are caused by falls, only one to two per cent of falls result in hip fractures. The risk for fracture during a fall depends on the mechanics of the fall and the use of specific protective responses, including landing on outstretched hands, contracting the leg muscles to absorb energy and rotating to prevent impact to the pelvis. While these responses are known, knowledge is lacking on how these responses are affected by age and whether they can be enhanced through education and physical training. Chantelle Murnaghan is developing an exercise-based intervention program for the prevention of hip fractures resulting from falls. The research will focus on developing an improved understanding of fall protective responses, including how these responses are affected by age, and by sensory and cognitive variables. Given the safety constraints of conducting fall experiments with the elderly, Chantelle’s study will involve young and middle-aged men in a series of lab experiments involving sideways and backwards falls, followed by a training program in safe-landing strategies. Results from this novel study will provide valuable new information for the development of more effective hip fracture prevention programs for the elderly.
An Empirical Test of Rational Polydrug Addiction
The economic model of rational addiction was a breakthrough in the economic theory of consumption of addictive substances. This model’s aim is to reliably estimate an addict’s change in consumption of an addictive substance due to a change in the drug’s price or the price of another drug to which the individual is addicted. Polydrug abuse within populations of heroin addicts has been observed within health services research literature for some time. Suggestions have been made to target treatment interventions and outcome assessment to multiple drugs, rather than a single drug in clinical trials involving substance abusers. Despite this, relatively little epidemiological research has been carried out to evaluate the effectiveness of different modes of treatment for drug abuse in polydrug addicts. Bohdan Nosyk is researching whether individuals addicted to more than one substance (e.g. heroin and cocaine) display some association in their consumption patterns of these substances. If there is a significant association in consumption, focusing treatment on one addiction may be ineffective given the increase in consumption within the other (untreated) drug addiction. This study will survey individuals addicted to multiple drugs residing in Vancouver’s Downtown Eastside to determine the relationship between illicit drug prices and consumption. Research into the addicted illicit drug consumer’s behaviour – in particular, how the consumer substitutes between substances and which drugs tend to complement one another – will provide policy-makers with evidence on which to base future directions in the treatment for addictive substance abuse.
System-based proteomic analysis of infectious Hepatitis C virus: towards the development of host-based anti-HCV therapeutic strategies
More than 123 million people worldwide are infected with Hepatitis C virus (HCV), including approximately 250,000 Canadians. There is no vaccine for HCV, and current treatments are less than 50 per cent effective against the predominant HCV genotype in North America. Since the outcome of HCV infection can be so severe and prevalence is so high, a better therapy is urgently required. Developing an effective treatment for HCV calls for a more detailed understanding of host and viral factors that influence infectivity of the virus. Through her research of two cell lines infected with HCV, Andrea Olmstead aims to gain a clearer understanding of the relationship between HCV and human cells. Although these two cell lines are related, the rate at which HCV multiplies in each of them differs. By exploring the significance of different patterns of protein expression between the two cell lines, Andrea hopes to identify novel interactions between host cellular proteins and HCV virus proteins that contribute to the outcome of infection. By uncovering host/virus interactions, her research may reveal new inhibition targets for generating effective therapies against HCV.
Interleukin (IL)-7 induced signals essential in T cell development and transformation
The molecule interleukin-7 (IL-7) is an important regulator of the development and signalling function of T cells, the white blood cells involved in fighting off infection and coordinating an efficient immune response. After T cells mature, they circulate through the blood, searching out invading pathogens, mounting an immune response and clearing the infection. This process generates specialized memory T cells, which are able to mount a stronger and more efficient immune response upon subsequent encounters with the same pathogen. Growing evidence indicates that not only is IL-7 essential in the development of these memory T cells, but that its overproduction is also implicated in a number of immune system cancers. Using a number of genetic models of IL-7 signalling, Lisa Osborne’s research will clarify the IL-7 mediated biochemical pathways necessary to ensure proper development and maturation of the T cell compartment, that are involved in the viability of mature T cells and the generation of memory T cells. She aims to demonstrate which molecule or pathway is primarily involved in the de-regulated growth of T cells that leads to cancer. Ultimately, this research could guide the development of vaccines that rely on the generation of memory T cells against a particular pathogen. Lisa’s work will also provide insights into the development of immune system cancers, and potentially a novel treatment approach.
Interaction and functional consequences of HCN channels and cytosolic SAP proteins in the cardiac sinoatrial node
Heart function is regulated in large part in the upper right hand corner of the heart, where a cluster of pacemaker node cells generate the pulsatile electrical signals that spread throughout the heart muscle. These signals cause the heart to rhythmically contract and relax, leading to the smooth flowing of blood through the circulatory system. In order to send pulsatile signals and coordinate the heart’s activity, pacemaker node cells possess a unique collection of proteins. This includes ion channels, that selectively permit charged ions to cross the membrane barrier surrounding cells, generating an electric field that can be spread to surrounding cells. A distinguishing feature of the pacemaker is that it spontaneously generates these electrical impulses. Specific ion channel proteins, called HCN channels, are largely responsible for this spontaneous activity. But how and why HCN channels express as they do in these pacemaker cells is largely a mystery. Christian Peters is exploring how the functioning, or even the presence of these proteins, is affected by their interactions with accessory proteins on the interior of the cell. By developing an understanding of these interactions, his research will contribute to our knowledge of the workings of a healthy heart, and contribute to the prevention or cure of ailments associated with a malfunctioning of the myocardium, the muscular tissue of the heart.
Developing innovative nanopharmaceuticals for the treatment of relapsed breast cancer
Therapeutic antibodies are a popular and effective class of cancer drugs, particularly when combined with more traditional treatments. While natural antibodies are found in our blood all the time, they do not recognize cancer. Therapeutic antibodies are designed to recognize special molecules found only on the surface of cancer cells, allowing them to target and kill those cells without harming healthy ones. This results in a dramatic decrease in the side effects of chemotherapy such as nausea, fatigue and hair loss. Little is known about how therapeutic antibodies work, including the reasons why they are ineffective in some cancer patients. This lack of knowledge currently makes it hard to adapt or improve the drugs. Jesse Popov is studying trastuzumab, a therapeutic antibody used to treat aggressive breast cancers. Focusing on revolutionary new theories about the way that cellular membranes function, Jesse is working to determine how trastuzumab works in the body, as well as the basis for trastuzumab resistance. With new insights, he hopes to uncover ways to tailor therapeutic antibody-containing pharmaceuticals to make them more effective in treating different forms of cancer. This research is part of the ongoing Breast Cancer Research Program at the BC Cancer Research Centre, an initiative focused on identifying pharmaceutically viable methods for improving the effectiveness of breast cancer treatment.
Role of Amyloid in Failure of Transplanted Human Islets
In Type 1 diabetes, beta cells are destroyed by the immune system, leaving the body unable to produce insulin. Type 1 diabetic patients inject insulin several times a day to normalize their blood glucose levels. Estimating the correct dose of insulin to administer is difficult: too much insulin leads to hypoglycemic shock, while chronic hyperglycemia (a shortage of insulin) can lead to organ damage and related complications such as blindness, kidney failure, neuropathies, vascular damage and pain in the limbs. The transplantation into diabetics of insulin-producing islet cells shows promise for relief from daily insulin injections and the development of diabetic complications. However, islet transplantation is in the early stages, and long-term rates of transplanted islet graft survival and maintained function are low: only 10 per cent of islet transplanted recipients remained free from insulin injections five years post-transplantation. Kathryn Potter is working to better understand the mechanisms underlying graft failure. In particular, she is interested in how stressors unrelated to immunity—such as pre-transplant and post-transplant hyperglycemia and the use of immunosuppressants—may cause dysfunction in transplanted beta cells and lead to graft failure. Her research may lead to modifications to current transplantation protocols that improve long-term islet transplantation success rates.