Despite public health efforts, sexually transmitted infection (STI) rates among young people are high and rising, with some groups of youth disproportionately affected. In particular, STI’s are a growing concern for youth living in northeastern BC’s oil, gas, and mining communities. These communities are experiencing rapid growth and social change, largely associated with an influx of young people attracted by the current economic ‘boom’ in the oil, gas and mining industries. Shira Goldenberg is investigating young people’s experiences accessing STI testing and treatment services in Fort St. John, British Columbia. She is examining how socio-cultural factors, such as social norms, gender, ethnicity, religion and structural forces, such as geography, economic restructuring, and public health service delivery mechanisms, affect young people’s experiences with STI testing and treatment. Shira will use this information to recommend ways public health planners can tailor STI interventions to improve the sexual health of youth in northeastern BC and other remote, resource-based communities.
Research Location: University of British Columbia - Point Grey
Regulation of antibiotic resistance and virulence by two-component response regulators in Pseudomonas aeruginosa
The bacterium Pseudomonas aeruginosa is a major cause of hospital-acquired infections and chronic cystic fibrosis lung infections. This pathogen is difficult to treat because it has the ability to sense and appropriately respond to changing environmental conditions. For example, it can sense and respond to the presence of antibiotics by becoming resistant, making the eradication of established infections extremely difficult. P. aeruginosa infections in cystic fibrosis patients are almost always deadly. An underlying mechanism for antibiotic resistance involves two-component regulatory systems – containing a sensor kinase and a response regulator – that enable bacteria to sense and respond to environmental signals. Two of these regulatory systems within P. aeruginosa have previously been shown to be involved in antibiotic resistance. Jamie Gooderham is determining whether other closely-related P. aeruginosa two-component regulatory systems are also involved in virulence and antibiotic resistance. To do so, he is generating bacteria defective in these systems and studying their virulence, gene expression, and responsiveness to antibiotics. These studies will increase understanding of how this pathogen adapts to environmental signals to develop antibiotic resistance. Ultimately, this will lead to more effective P. aeruginosa therapies, improving treatment outcomes for infected patients.
Respiratory system limitations during exercise in women undergoing healthy aging
There is evidence to suggest that healthy men and women experience respiratory system limitations during exercise, such as respiratory muscle fatigue, a limited ability to exhale, and an abnormal exchange of oxygen and carbon dioxide in the lungs. Young active women may be particularly susceptible to these limitations due to their inherently smaller lungs and airways compared to men of equal stature. Unfortunately, there have been few studies aimed at understanding how the female respiratory system responds during exercise. Since healthy young women are predisposed to these limitations during exercise, then healthy elderly women may be particularly vulnerable due to the decline in lung function that occurs as a result of the normal aging process. This decline occurs because of a reduction in “elastic recoil,” which is the ability of the lungs to stretch and inflate. Jordan Guenette is studying the relationships between the respiratory system, exercise, gender, and healthy aging. His goal is to identify the respiratory limitations women face as they age. This information could be used to design exercise rehabilitation programs tailored to meet the needs of different patient populations.
Somatic and gametic loss of imprinting (LOI) in mammalian development: studies using a novel imprinted transgene on the mouse distal choromosome 7 (MMU7) imprinted region
Genetic inheritance in an offspring primarily results from the interplay of dominant and recessive genes between two parents. With certain genes, however, gene expression is parent-of-origin-specific: these genes will always be expressed from either the maternal or paternal chromosome. This process is known as genomic imprinting, which creates a mark, or “imprint”, on the chromosome. Loss of imprinting (LOI) is often studied in the context of disease, especially in cancers, but it is also a normal part of development. For example, in germ cells, imprints are erased and re-set early in development every generation, resulting in a normal period of LOI. Meaghan Jones is investigating a hypothesis that non-germ cells may also experience some normal LOI during development. She will examine the timing, stimulus and duration of LOI in germ cells and somatic cells during development. By determining the various causes of LOI in both types of tissues, she hopes to uncover factors regulating normal LOI and help alleviate the risk of imprinting defects.
Activation of NR2A-containing NMDA receptor-mediated cell survival as a novel and innovative therapeutic strategy in the treatment of stroke
Stroke is a major cause of death and disability in North America. Major efforts have been placed into blocking mechanisms of excitotoxicity following stroke. Immediately after the onset of stroke, a plethora of glutamate is released in the affected area, and activation of NMDA-receptor by glutamate has been attributed to be the main cause of neuronal damage during stroke. Nevertheless, clinical studies of stroke patients given NMDA-receptor blockers have proven to be disappointing. It has been suggested that NMDA-receptor blockers are efficacious only when given prior and/or soon after stroke onset. Once the receptors and downstream death signaling cascades are activated, blocking NMDA-receptor is no longer useful. Since stroke patients often reach the hospital and receive their diagnosis several hours after stroke onset, the conventional therapeutic strategy of blocking NMDA-mediated cell death is not clinically useful. Surprisingly, our preliminary study suggested that only the NR2B subunit-containing NMDA-receptors (NR2BR) promote cell death, and paradoxically, the NR2A subunit-containing NMDA-receptors promote cell survival (NR2AR). We propose that selective activation of NR2AR-dependent cell survival may be a more effective stroke treatment strategy than blocking NR2BR-dependent cell death. In addition, because we are proposing to promote cell survival and not blocking cell death, our treatment should be effective even when administered along time after stroke onset.
The Determination of Accessibility to and Utilization of Fair PharmaCare by Various Ethnic Minority Groups
Since the mid-1990s, North American prescription drug expenditures have been escalating at double-digit rates. Canadians spent $18 billion on prescription medicines in 2004. The rising cost of prescription drugs has raised concerns about the affordability of health care for Canadians. Provincial drug coverage programs within Canada employ diverse strategies for reimbursement. In British Columbia, an income-based drug benefit plan is utilized. This program, dubbed Fair PharmaCare, requires residents to register with the government to be eligible for public subsidy. Vivian Leong is evaluating levels of participation in the Fair PharmaCare program in different socioeconomic and socio-cultural communities to determine the factors that influence access among ethnic minorities. Vivian will identify whether some groups have unequal access to pharmacare subsidies, and if so, why the inequity exists. She is also assessing whether provincial government efforts to promote awareness among minority groups have been effective. This research will help policy makers address inequities and target health promotion to reach and better serve various ethnic communities in British Columbia.
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.
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.