HIV risk environments among illicit drug users: A longitudinal ethno-spatial approach

Dr. Will Small’s research program will examine the influence of social, structural and physical environments upon illicit drug users’ HIV risk behaviour and HIV treatment-related outcomes. The study is nested within a larger program that includes three epidemiological cohort studies of adult drug users and street-involved youth. This approach integrates ethnographic observational fieldwork, in-depth interviews, and geo-spatial mapping techniques with quantitative laboratory and survey data to identify how the social, structural and physical features of drug-use scenes impact HIV outcomes.

Informed by ecological perspectives on health, and the HIV risk environment framework, this study will develop and pilot a novel ethno-spatial approach to identify the complex pathways and dynamics between contextual factors shaping the risk environments of drug use and HIV prevention and treatment for drug users. Building on 10 years of experience studying illicit drug use and HIV/AIDS in the local context, this program of ethno-spatial epidemiology seeks to address the following specific aims:

  1. Examine the influence of evolving social and physical features of “drug scenes” on HIV risk behaviours and HIV incidence among drug users.
  2. Assess the influence of evolving structural and physical factors on critical initiation and transitional events (e.g. initiation into drug use or sex work; transitions in drug use patterns) among drug users and inform epidemiological models of HIV risk.
  3. Examine the impact of evolving structural and physical factors on initiation and adherence to antiretroviral therapy and suppression of HIV-1 RNA among HIV-positive drug users.
  4. Create a platform for the ongoing ethno-spatial evaluation of future public health and public policy interventions targeting drug users.

Manipulating the trajectory of the human fetal, newborn & infant immune system

Millions of newborns and infants die each year from infectious diseases. Many of these deaths are preventable, and analysis of the immune development of children can help define paths for medical intervention that may save lives.

Dr. Tobias Kollmann’s research team is conducting the first global comparison of immune development in cohorts of children from different countries. This project will compare the immune development of children born in Vancouver to those born in South Africa, Mozambique, Ecuador and Belgium. Preliminary research has found striking qualitative and quantitative differences in children’s immune development that appear to be directly related to their genetic make-up as well as the particular environment to which they are exposed. Kollmann’s team is dissecting the cause-effect relationship for the role of host genetics and studying the environmental factors that direct the developmental path of the innate and adaptive immune responses. Analysis of these genetic and environmental factors will potentially reveal pathways that direct future efforts to treat and prevent infectious diseases.

Kollmann’s team is already developing a platform that will help deliver targeted vaccinations to protect newborns. Using genetically altered strains of Listeria monocytogenes, the vaccine will induce a desired immune response only in specific cells and then disappear without harming the child. Preliminary data suggest this goal is within reach, and Kollmann’s team is working in partnership with industry to design and test a Listeria-based vaccination for newborns. Through this work, safe yet effective methods will be identified to prevent millions of newborn and infant deaths due to infectious diseases.

Linking socioeconomic status to environmental pollution exposures over the life course: population-based research using biomarkers to investigate the effects of exposure on small for gestational age …

Dr. Scott Venners is studying the impact of exposures to environmental pollutants and their links to health inequalities between richer and poorer people, specifically small size at birth and diabetes in adulthood. As in many Canadian cities, babies born to mothers in socially and materially poorer parts of Vancouver are more likely to be born under-sized than those born in other parts of the city, and higher levels of second-hand smoke exposure may be a factor.

Venners will test exposure to second-hand smoke by measuring cotinine (a byproduct of nicotine) in serum (blood) samples from non-smoking pregnant women. He will then investigate whether non-smoking women with higher levels of serum cotinine (and thus with higher second-hand smoke exposures) are more likely to have a baby that is too small. The project will also test whether some babies are genetically more susceptible to adverse effects of second-hand smoke during pregnancy. Finally, Venners will test whether non-smoking pregnant women who live in poorer areas of Vancouver have higher levels of serum cotinine compared to others, which would suggest that they were exposed to more second-hand smoke. This evidence will provide a better understanding of whether reducing exposures to second-hand smoke will reduce disparities between poorer and richer areas in the likelihood a baby will be born too small.

In addition to passive smoking, the project will study other important classes of pollutants that may be linked to small size at birth. The project will also study the links between socioeconomic status, exposure to mixtures of persistent organic pollutants in adulthood, and inequalities in diabetes risk between richer and poorer Canadians.

HIV adaptation to immune selection pressures: historic trends and future implications

HIV has tremendous capacity to mutate and evolve due to the body’s immune response. However, the extent to which the virus has adapted to its human hosts over the course of the pandemic remains poorly understood. Repeated cycles of immune selection and transmission may allow the accumulation of key “escape mutations” — changes in the viral genome that help HIV evade the body’s defences. If immune targets in the HIV genome were disappearing over time due to the accumulation of these mutations, our ability to generate natural and vaccine-induced protective immune responses would diminish as the epidemic progresses.

Furthermore, the extent to which immune escape has influenced HIV pathogenesis remains unknown. Studies investigating the evolution of HIV virulence have largely focused on population-level trends in clinical markers over time, but few have addressed this issue using biological assessments of replication capacity or viral protein function.

Dr. Zabrina Brumme’s research team will undertake the first large-scale investigation of immune-driven HIV evolution and its implications over the 30-year history of the epidemic in North America. Host and viral genetic sequences from 1979 to the present will be analyzed to characterize the extent of population-level HIV adaptation over the epidemic’s course. Functional assessments of viral replication capacity and protein function will be performed to determine whether HIV is evolving towards increased virulence, gradual attenuation, or simply adapting to changing host-pathogen pressures over time.

With this study, Brumme is poised to answer two key questions of HIV biomedical research, namely, to what extent the virus has adapted to its hosts since AIDS was first recognized, and what implications this has for the future of the epidemic. Results have the potential to significantly advance HIV vaccine research.

Training parents as friendship coaches for children with Attention-Deficit/Hyperactivity Disorder

Attention-Deficit/Hyperactivity Disorder (ADHD) is a syndrome marked by inattention and/or hyperactivity/impulsivity that affects 5-8 percent of Canadian youth. It makes up the most frequent referral for children’s mental health services and is associated with considerable psychosocial morbidity. A significant aspect of the impairment in ADHD is the difficulty these children face in getting along with peers. More than half of children with this condition are severely disliked by their peers or do not have a single friend. Peer problems result in loneliness and sadness for children with ADHD, and heighten the risk for future school failure, drug abuse, and delinquency. Treatments for the core symptoms of ADHD are ineffective at changing peers’ liking of children with ADHD, and if existing treatments do not also improve peer relationship problems, children with ADHD remain likely to experience poor health outcomes. These findings underscore the importance of developing adjunctive treatments capable of addressing the peer problems faced by children with ADHD.

Dr. Amori Mikami’s research focuses on the development, efficacy testing, and knowledge translation of novel psychosocial interventions for peer problems in children with ADHD. She proposes to expand upon an innovative intervention: training parents to improve the peer relationships of their children with ADHD. This is known as parental friendship coaching (PFC). Supported by the National Institute of Mental Health, Mikami created the PFC intervention and demonstrated in a randomized trial of 62 children with ADHD that PFC appeared effective relative to a no-treatment control group.

Mikami is following up on these promising preliminary results with a more definitive test of PFC and a better study of the mechanisms behind treatment efficacy. She will compare PFC against an active attention control intervention (to ensure the incremental value of the PFC techniques beyond social support and therapist time), involve 150 children from two diverse areas in Canada, follow up with participants eight months post-intervention, and use a thorough battery to measure outcomes, mediators, and moderators. Future studies will focus on disseminating new knowledge about PFC and peer problems to practitioners.

Responding to the health crisis among street-involved youth in Vancouver: Evidence to inform interventions and policy responses

Street-involved youth are extremely vulnerable to health-related harms resulting from high rates of illegal drug use and sexually-risky behaviour, poverty, and neglect, as well as precarious living conditions, either on the street or in risky relationships. There is an estimated 150,000 street youth in Canada, with approximately 40 percent reporting injection drug use. This puts street youth at a very high risk for sexually transmitted infections (STI) and hepatitis C (HCV) infection.

Dr. DeBeck’s research seeks to address gaps that exist in our understanding of how street youth are initiated in illegal drug use and the dynamic of how STI and HCV are transmitted.

Her work will examine individual (e.g. stimulant use), social (e.g. childhood trauma), structural (e.g. access and coverage of addiction treatment), and environmental (e.g. homelessness) factors and how they intersect to promote a “risk environment” that elevates sexual risk and drug-related harms.

The outcome of her analysis will be a body of evidence that can support the development and evaluation of behavioural and structural interventions to prevent sexual and drug-related harms among street-involved youth. Her work will also support clinical trials to address critical issues in the diagnosis and treatment of hepatitis C among street-involved youth.

Ultimately, the results of her work will help prevent high-risk drug use, infectious diseases and other health harms among street-involved youth. It will also provide critical guidance for the effective management and treatment of infectious diseases among street involved youth.

Characterization of the formation of protein aggregates induced by the inhibition of the ubiquitin proteasome system

Protein aggregation is a pathological feature of a large number of diseases with a strong preponderance in age-related neurodegenerative disorders like Parkinson’s disease. Failure to eliminate aberrant proteins in the cell plays a major role in these pathologies and is often linked to the impairment of the ubiquitin proteasome system, which degrades proteins labeled (or modified) with ubiquitin. The overall goal of Dr. Thibault Mayor’s research is to further define the involvement of the ubiquitin proteasome system in aggregation diseases using proteomic and cell biology approaches.

Mayor’s team has developed a new cellular assay to monitor the formation of aggregates induced by proteasome inhibition. They have identified by mass spectrometry more than 500 proteins that localize in these structures. Using a computational approach, Mayor will determine which features are shared among these proteins to give better insight into the mechanisms leading to aggregation. The UCHL1 enzyme may also be a major player in the aggregation process, and Mayor’s team will use the cell assay and mass spectrometry to further characterize UCHL1 and determine whether other enzymes related to the ubiquitin proteasome system may promote aggregation.

Current treatments for most aggregation diseases are primarily based on symptom management instead of directly treating the cause. Mayor’s work may potentially lead to a better understanding of the aggregation mechanism and identify novel targetable pathways to prevent formation or favor clearance of protein aggregates that could be used for new therapeutics.

Understanding tumor microenvironment interactions in lymphoid cancers: Translation into improved treatment outcome prediction and development of personalized therapies

Malignant lymphomas are the fifth most frequent cancer in humans, affecting patients of all ages. Despite generally effective treatments, a significant number of patients still die from the progressive disease. Interactions of the malignant cells with cells of the tumor microenvironment are increasingly recognized to play a pivotal role in the development of many lymphoma subtypes. However, the clinical potential of an improved understanding of microenvironment-related biology remains largely untapped.

Dr. Christian Steidl’s research focuses on B-cell lymphomas; in particular on the two related subtypes — Hodgkin lymphoma and primary mediastinal B-cell lymphoma — that often affect adolescents and young adults. This study will investigate tumor microenvironment interactions as therapeutic targets in B-cell lymphomas. Steidl’s team will seek to elucidate the underlying pathobiology of the tumor microenvironment, and macrophage interactions in particular, to identify novel drug targets and pave the way for the design of innovative clinical trials.

The study will also identify outcome predictors and resistance mechanisms of childhood and adult Hodgkin lymphoma. Molecular treatment outcome predictors will be developed using genomics approaches. Better outcome prediction using biological markers will identify patients at high risk and allow for personalized treatment approaches for children and adults suffering from relapsed Hodgkin lymphoma. Specifically, the recent emergence of novel targeted therapies holds the promise to overcome this high risk using these therapies to augment or replace existing therapies.

Finally, this research will define the mutational landscape of Hodgkin lymphoma and primary mediastinal B-cell lymphoma. This will involve the complete characterization of mutations by next-generation sequencing approaches. Preliminary data indicate that somatic mutations in both diseases are critically deregulating molecular pathways that might be targetable by novel therapeutic approaches. These studies will aim to transform novel findings into meaningful advances in clinical hematology.

Health, Creative Arts, and Northern Communities

With the highest rates of premature mortality at 3.71/1,000 people, the Northern Health Authority has the lowest health status in BC. Dr. Sarah de Leeuw’s research seeks to address this issue by examining how creative arts and the humanities can help resolve health inequities experienced by Indigenous and non-Indigenous people in northern BC.

To do this, she will draw on her previous research as well as growing global evidence that shows how medical humanities and health-based creative arts can enhance well-being. She will also look at how social determinants of health frameworks can explain health disparities.

She will lead a team of northern BC community advisors, health researchers, and medical/health science students. The team will develop and deploy multi-disciplinary creative methods and methodologies to harness, document, translate, and disseminate existing northern strengths – especially First Nations’ – as a population health and wellness initiative.

Her research will:

  • Advance new methods, approaches, and models – anchored in creative arts and social determinants of health frameworks – that produce and translate innovative ways of addressing health inequities.
  • Promote rural, northern and First Nations communities through the creative arts as places where health service providers want to live and work.
  • Use creative arts to increase interest by locals – particularly First Nations – to pursue health and medical education and training within the region and to then stay in the region.
  • Encourage multi-disciplinary cross-community collaborations.
  • Augment northern health education curricula (nursing, social work, medicine, community health) with accessible, targeted, and affecting knowledge.
  • Circulate strengths-based evidence about populations in the Northern Health Authority – especially First Nations – beyond the borders of the health authority with the intent of encouraging southern, urban, and non-Indigenous British Columbians to feel vested in the wellness of BC’s northern populations.

A wearable assistive device for improving quality of life

Mobility of the upper extremities has a significant impact on independence and quality of life. For individuals with neuromuscular disorders due to aging, stroke, injury, or other diseases, the activities of daily living (such as eating and dressing) can be very challenging. However, biomedical robotic technologies offer a promising tool with which to improve the mobility of individuals with impaired upper extremities.

Collaborating with experts in the field of neuromuscular rehabilitation, Dr. Carlo Menon is leading the design and development of a smart assistive medical device that is portable and wearable. The objective is to develop a device that will assist with functional movements and strengthen muscular tone of the weakened or impaired extremities. The device will have potential use for both upper extremity assistance and rehabilitation.

This research will improve the quality of life for individuals with neuromuscular disorders by restoring mobility of the upper extremities. The proposed project will include the following phases: a) interaction with the neuromuscular collaborators to iteratively reformulate the design; b) the engineering design and development of the biomedical robotic device; c) the engineering testing of the device; d) a study of the interactions between the device and both healthy volunteers and individuals with neuromuscular disorders to verify that the device can assist functional movements; e) technology transfer to neuromuscular scientists and clinicians.