Cancer causes six million deaths worldwide each year, and is the second leading cause of death in developed countries. Of 227,000 new cases diagnosed in Canada this year, about 80 per cent will be some type of carcinoma, a malignant tumor that begins in the epithelial cells lining the inner and outer surfaces of our organs. Carcinomas comprise a vast array of cancers, including lung, breast, prostate, colorectal, oral, esophageal and cervical. Although current treatments can be effective, survival rates vary for these different types of cancer. Mutations in genes are responsible for the development of all cancers. But the nature of epithelial cancer cells makes it difficult to distinguish which mutations initiate the process. William Lockwood is using new technology to define patterns of DNA change in people with early stage epithelial cancer and to identify the genes responsible for the progression of the disease. Ultimately, these genes may be used to predict which pre-cancerous lesions are prone to develop into tumours to improve early detection and treatment.
Program: Trainee
An Internet-based self monitoring intervention for patients with chronic heart failure
In 1997, congestive or chronic heart failure (CHF) was the primary cause of death in British Columbia and in 2000, it was the most common cause of hospitalization for Canadians over the age of 65. Multidisciplinary interventions, including education, follow up and self-management strategies have been shown to improve quality of life and decrease subsequent hospital admissions among people with CHF. However, up to 50 per cent of hospital readmissions for CHF occur because patients have not learned to manage and monitor their condition effectively. Biljana Maric’s research is investigating the feasibility of Internet-based self-monitoring for CHF patients. Participants will log on to the study website each morning, enter their current body weight and answer five questions about their health status and any symptoms they are experiencing. A nurse will log on to a secure database to monitor responses and follow up with participants when responses trigger an alert. Biljana’s study will examine patient and staff uptake, and assess the impact of the program on patient quality of life and self care. If adopted, Internet monitoring of heart patients could decrease the health care costs associated with heart failure readmissions, alleviating some of the financial burden on the health care system while improving patient health outcomes.
T Cell Therapy of Breast Cancer: Defining and Circumventing Barriers to T Cell Infiltration of the Tumour Microenvironment
T cells are white blood cells involved in a variety of our immune system responses, including detection and destruction of cancer cells. With T cell therapy, “tumour-reactive” T cells are isolated from a patient’s blood, and large numbers are grown outside the body. These T cells are then infused back into the patient to help the body recognize and destroy cancer cells, a method called adoptive immunotherapy. Michele Martin is studying the potential for using T cell therapy to treat breast cancer. Early results show about 19 per cent of tumours will regress or shrink with this treatment – unprecedented with other types of treatment – while the rest have partial or no regression. Michele is investigating how some of the tumours manage to exclude the T cells and also whether combining T cell therapy with low doses of chemotherapy can facilitate T cell infiltration into these tumours. If successful, this approach could improve breast cancer cure rates and reduce the side effects associated with current treatments.
Prefrontal-cortico-amygdalar circuitries underlying cue-induced reinstatement and the effects of amphetamine sensitization on responding for food reinforcement
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.
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.