Because antiretroviral therapy has enabled people to live longer, those with HIV now face a growing epidemic of age-related chronic diseases such as chronic obstructive pulmonary disease (COPD). The reason for this increased risk, however, remains unknown. Compelling evidence suggests that HIV infection triggers an inflammatory process which causes the premature aging of inflammatory and structural cells due to cell exhaustion from repeated divisions and oxidative stress. This concept of “inflamm-aging” (coined by Claudio Franceschi) applies fittingly to the development of COPD as well, where the primary trigger is cigarette smoke.
Given the dual pro-inflammatory states of HIV and COPD, Dr. Leung hypothesizes that the accelerated development of emphysema in HIV is driven in part by inflammation-induced cell aging related to the HIV infection and potentiated in the lungs by cigarette smoke. Dr. Leung's laboratory has found peripheral leukocyte telomere lengths, a marker of cell senescence, are shorter in HIV-infected patients who also have COPD compared to HIV-infected patients without COPD. Those with the most severe airflow obstruction on spirometry and those with the greatest extent of emphysema as visualized on CT scanning also appear to have the shortest telomere lengths. The laboratory group is now exploring whether similar relationships hold in lung cells obtained from HIV-infected patients.
In Canada, stroke is the third leading cause of neurological disease and death. Although improved acute care has resulted in greater survival rates, an increased number of Canadians suffer long-term neurological disability and a decreased quality of life following a stroke. With an aging Canadian population, the need for efficient and effective diagnostic tools and rehabilitation strategies are critical so that stroke survivors can maintain independence and a high quality of life. Currently, the assessment of recovery and motor learning after a stroke focuses on neuroimaging techniques that indicate the status of gray matter within the central nervous system, which consists primarily of cell bodies. However, data characterizing how white matter supports motor learning and recovery after a stroke has been notably absent.
The goal of the study is to explore and understand the mechanisms associated with learning-dependent changes of white matter in the central nervous system. The proposed research plan will attempt to, firstly, understand whether motor learning is associated with changes in the white matter micro-structure and, secondly, relate changes in brain structure and neurophysiology to learning and functional recovery after stroke.
The intended research will provide unprecedented insight into areas of the stroke-injured brain that respond to motor learning. More importantly, this work will enhance the understanding of the effects of motor learning on functional recovery and generate the opportunity to develop novel therapeutic interventions for the growing population of individuals living with the after-effects of stroke.
Lymphoid cancers arise from lymphocytes, a subset of white blood cells, and represent the fifth most common cause of cancer. Follicular lymphoma (FL) is a common subtype of lymphoid cancers. For ten percent of FL patients, the disease either does not respond to primary therapy or progresses early after treatment. These patients have poor outcomes and often require aggressive therapeutic interventions.
With regards to its origin, FL demonstrates how cancers arise through the successive acquisition of changes in their genomes. In his research, Dr. Kridel’s group has identified highly recurrent mutations in certain genes which delineate disease-initiating mechanisms. Yet, the biological underpinnings of treatment resistance and transformation in FL are only partially understood.
Dr. Kridel hypothesizes that both resistance to therapy and transformation can be explained by genetic alterations that are either present at diagnosis and get selected for during therapy, or that arise during the course of the disease. Thus, Dr. Kridel’s team will apply high-throughput genome sequencing technology to paired FL and progressed/transformed lymphoma samples. Dr. Kridel will leverage the availability of tumour specimens from the tissue repository of the Centre for Lymphoid Cancer at the BC Cancer Agency and collaborate with the Computational Biology group of Dr. Sohrab Shah, who has developed cutting-edge tools to examine genome-wide mutational changes.
The goal is to improve patient outcomes by understanding the genetic mechanisms that drive treatment resistance, early progression and transformation in FL.
Chemotherapy is one of our strongest weapons for treating cancer, but it also harms healthy cells and causes serious side effects in patients. Researchers at the Hieter Laboratory at the University of British Columbia in Vancouver hope to develop a more targeted approach, one that takes advantage of the genetic changes that exists in cancer. Their approach identifies which combination of genetic changes will selectively kill cancer cells. Answering that question will be key to developing new targeted drugs to fight cancer.
Cancer cells often contain multiple gene mutations or changes which affect the stability of the genome, but whether this instability is a cause or consequence of cancer remains to be understood. A project led by Dr. Supipi Kaluarachchi Duffy is using high throughput genetic screens, overproducing one gene at a time in yeast, to identify which genes lead to genome stability. She will then identify genetic changes that are common in both yeast and human cancers and leverage these to find secondary genetic targets. Yeast is a great model organism for this work because it shares many of the fundamental biological pathways that are essential for life.
“The first step is distinguishing between a gene whose overproduction contributes to genome instability and a gene that has no effect,” says Duffy. “The end result would be more targeted chemotherapy at lower doses and with fewer side effects.”
Studies reveal that transgender and gender non-conforming people experience pervasive and multiple forms of violence in numerous public and private places, suggesting they may be more vulnerable to violence across their lifespan than the general population.
This study will develop knowledge about the intersections between violence, gender identity/expression, place, and mental health in the lives of transgender and gender non-conforming people. It will investigate the strategies people use to prevent and resist violence and maintain their mental health. The study will also explore how different geographic contexts, gender discrimination, racism, and/or poverty undermine or enhance safety, belonging, resiliency, and mental health.
The proposed study will use Photovoice, a community-based participatory research method that combines photography, dialogue, and social action. The study will be conducted in two sites (Vancouver and the Okanagan Valley) in order to investigate similarities and differences between large and smaller cities. This research will include in-depth, semi-structured photo-elicitation interviews and focus groups where participants will discuss the meanings and stories portrayed in the photographs.
This research will provide an in-depth understanding of how the enforcement of gender norms impacts the mental health and well-being of Canadians. It will have broad implications for the development of best practices and protocols for trauma-informed and gender-sensitive services, health promotion, and violence prevention/intervention in marginalized communities.
The development of resistance to commonly used antiviral drugs Relenza and Tamiflu has become a serious problem facing the world. It is reported that 98 percent of influenza A/H1N1 strains in North America are resistant to Tamiflu. The Withers group has designed a series of sialic acid analogs in which the C-2 OH group was replaced with fluoride to trap the virus by the formation of a covalent intermediate. To slow down the reactivation rates of neuraminidase, an electronegative flurorine was introduced at C-3 position to destabilize the positively charged transition state en-route to the formation and hydrolysis of the covalent intermediate. In addition, to confer specificity for the influenza neuraminidase over human sialidases, a positively charged nitrogen substituent was incorporated by analogy with the design of Relenza and Tamiflu. Those compounds showed very promising properties against the influenza virus.
Dr. Zhizeng Gao proposes to take advantage of the mechanism of action of this class of inhibitors, and develop a set of fluorescent and fluorogenic neuraminidase probes. Such probes share structural similarities with the inhibitor but the fluorine at C-2 was replaced with latent fluorophores, or C-7-OH was linked with fluorophores. Such probes are useful for investigation of the presence and role of neuraminidases in biological systems, especially if their presence or activity can be detected, quantitated and in some cases localized.
A growing body of evidence has shown that violence and other health-related risks are highly gendered, with a disproportionate burden experienced by young women and youth who do sex work in many settings. In Vancouver, escalating gentrification, the recent creation of supportive housing for “at-risk” youth, and legislative shifts in criminal policies around sex work and drug use have the potential to transform the landscape of violence, risk, and safety that youth who do sex work must navigate.
The proposed ethnographic study will explore how these processes of urban transformation are altering youth’s experiences and health outcomes over time. Key focuses will be youth’s social-spatial transitions in sex work (e.g. the transition from more isolated outdoor spaces to potentially safer indoor venues), and how these transitions exacerbate or mediate the production of violence and risk.
This research will be particularly concerned with how gender relations and inequities intersect with the production of violence and risk in particular sites. Moreover, it will focus on the continuum of violence experienced by youth in the city and how structural violence can produce interpersonal violence and risk in particular places.
This study will help produce a more nuanced understanding of young people’s lived experiences in the city over time, and the gendered production of risk and violence in urban space. This understanding is critical to developing and advocating for policy and “safer environment interventions” that are relevant to youth’s needs and capable of addressing the complex social processes that shape health outcomes for this youth population.
