Scholar – Page 20 – Health Research BC

Habitual Physical Activity as Stress Resiliency in Populations Experiencing High Adversity

In light of extensive research linking stress and disease, and the high rates of reported stress in Canadians, there is a need to identify what people can do to protect their health from the ill effects of stress.

My work to date demonstrates that highly stressed and active individuals have significantly healthier biological and psychological stress responses than those who are highly stressed and inactive. This model suggests that physical activity could be helping to protect active individuals against the disease-promoting influences of stress.

This program seeks to clarify whether this is a cause-and-effect relationship. Is the better health of active individuals merely a result of traits that also cause them to remain active when under stress? Or can highly stressed, inactive people also gain these health advantages through interventions that increase their physical activity levels?

Goals of this program include:

Discovering whether increasing habitual physical activity levels in highly stressed and inactive adults reduces the impact of stress on pathways to physical disease.
Developing novel targets for evidence-based intervention programs tailored to individuals with high levels of life stress

Collaboration with researchers, stakeholders in high-risk populations, and policy makers will support the design of interventions that target biological and psychological stress-reactive pathways years before disease appears.

By focusing on health promotion in high-adversity communities, the ultimate goal is to improve quality of life and to reduce the economic burden on our health care system.

Responding to HIV and other blood-borne pathogens among people who use illicit drugs

The intertwined pandemics of addiction and HIV/AIDS remain a public health crisis. Among people who use drugs, a substantial number live with HIV/AIDS and many experience suboptimal treatment outcomes.

Efforts to control the spread of HIV/AIDS through scale-up of HIV testing and treatment has been shown to be effective in the general population. However, the strategy has yet to be fully evaluated among groups of people who use drugs. To control the spread of HIV/AIDS in these groups most effectively, more information is needed about the effects on them of social/ structural exposures such as criminalization, marginalization and impoverishment.

This five-year program aims to produce scientific evidence to improve the health of people who are addicted to illicit drugs by targeting the associated blood-borne infections, in particular HIV and hepatitis C, along the following framework:

Identifying modifiable social/structural and environmental barriers to optimal outcomes for HIV and hepatitis C treatment, informed by the risk environment framework.
Modelling model social/ structural and environmental factors that affect HIV viral load and new HIV infections at the community level, in the context of BC's province-wide HIV treatment-as-prevention effort.
Evaluating the effects on outcomes of HIV treatment of various aspects of the local healthcare systems, such as harm-reduction-based outpatient ART adherence support interventions, using causal inference approaches.
Evaluating the uptake and effectiveness of DAA and identifying barriers to successful treatment among drug users infected with both HIV and hepatitis C.

The ultimate goal is to control the spread of HIV/AIDS and improve the health of British Columbians by combining clinical and social epidemiologic approaches to identify the social-structural drivers of ill health and effective evidence-based healthcare interventions.

A Research Program to Ensure the Effective Delivery of Substance Use Treatment Across Acute and Community Care Settings

Substance use disorders are a major contributor to preventable illness and death, including HIV and hepatitis C infection. An effective response to this public health crisis depends on using evidence-based practices in acute and community care settings (addiction health care) to understand factors that influence access to health services and people’s drug use.

This program examines health care and substance use through three interconnected lines of inquiry:

Collaborating with peer-based support organizations in the community to explore social, structural, and physical influences shaping access to and engagement with substance use treatment.
Employing implementation science approaches to examine individual, social, and structural influences on the uptake of evidence-based practices in addiction health care through examining a) local and regional implementation of newly released regional guidelines for the clinical management of opioid dependence, and b) the recent integration of evidence-based practices in addiction health care in a range of settings.
Examining the perspectives and experiences of people who use drugs in relation to evidence-based practices in addiction health care and the impacts of these practices upon a) substance use treatment access and retention; b) addiction health services access and engagement, including HIV and hepatitis C treatment; and c) overdose risks.

Ultimately, this project seeks to integrate community-based and implementation science approaches to inform how we can increase the responsiveness of substance use treatment programs to the needs of people who use drugs and of health care professionals.

A comparative and cross-jurisdictional research program on work and health

This project seeks to improve our means of developing social, economic, and workplace policies that improve worker health and reduce worker health inequalities. It builds on existing stakeholder collaborations and is structured around a series of comparative and cross-jurisdictional studies on occupational health and safety and workers’ compensation.

The broad aim of this research program is to expand current comparative research in order to develop an enduring policy and practice network that creates research and data infrastructure and a knowledge exchange and mobilization node that will support improved practices.

This program builds and extends data and research partnerships among researchers, compensation boards, and insurers from Canadian provinces, Australian states and New Zealand.

It has five objectives:

Build and expand the network of compensation boards, researchers and other stakeholders to create a forum and group that can identify, guide and inform the focus of the cross jurisdictional policy comparisons.
Expand the current comparative cross-provincial dataset on workers’ compensation to include all Canadian compensation boards’ data and a broader set of comparable variables.
Work with international partners to create a more limited set of comparable data that would permit comparisons between different countries.
Conduct policy-relevant, hypothesis-driven research with the comparative data to examine differences in and the effectiveness of different approaches to improving work disability outcomes.
Utilize the policy and researcher network to effectively translate the results into policy and practice.

The vision of this research program is to advance our understanding of work-related disability and facilitate the translation of results into policy and practice.

Translational Proteomics and Systems Biology of Pediatric Malignancies

In Canada, cancer is the leading cause of disease-related death in children beyond the newborn period. Each year, more than 3,000 Canadian children, adolescents, and young adults are diagnosed with cancer. Childhood cancer survivors with secondary cancers in adulthood are the sixth most common form of adult cancer, and late effects of cancer treatment are estimated to cost $1 million per child over their lifetime.

An improved understanding of disease and treatment mechanisms at the systems level could improve our ability to treat cancer. This project addresses two fundamental questions in pediatric cancer biology by integrating advanced protein analysis of patient tumor biopsies with cell and computational models:

Can we identify new drug and diagnostic targets for difficult-to-treat and relapsed cancers?
How can we improve treatment specificity for late effects?

This project focuses on changes in proteins produced by cells with DNA mutations associated with cancer. A single gene can give rise to a whole spectrum of variant and modified proteins, or "proteoforms", through a process called post-translational modification. This process can happen differently for genes that bear mutations associated with cancer, giving rise to a noticeably different panel of proteoforms.

This altered pool of proteoforms is a potential source of cancer diagnostic markers and cancer drug targets. The protein experts in this project team aims to work with the genomics experts at the Child & Family Research Institute, Genome Sciences Centre, and BC Cancer Agency to synergistically study next-generation signature-based biomarkers, drug targets, and innovative drugs.

The ultimate goal of the project is to contribute to improved quality of life for childhood cancer survivors, reduce the socio-economic burden, and add to treatment options for children with cancer.

Intravascular Materials to Control Thrombosis and Haemostasis

Uncontrolled bleeding is a leading cause of death worldwide. Specifically, postpartum hemorrhage leads to maternal death in 1-2 percent of all births in low-resource settings, while hemorrhage due to trauma is the largest killer of young people worldwide. Conversely, undesired clotting, or thrombosis, is a leading killer of Canadians because it causes strokes and heart attacks.

New drugs have led to advanced treatments for thrombosis and hemorrhage. Attaching the drugs to carrier materials that target sites of damaged blood vessels would further improve the treatments. Biological materials that target damaged blood vessels already exists in nature, providing a guideline for developing improved targeting materials: platelets and blood clots adhere selectively to injured vessels to stop bleeding.

This project will investigate the components and mechanisms that cause blood clots to selectively adhere to injured blood vessels. It will also use these findings to explore ways to engineer new materials that mimic these properties to target drugs to damaged blood vessels.

One material we recently developed self-propels through blood flow and deep into wounds to deliver drugs that help stop bleeding. It was highly effective in large animal models of fatal hemorrhage by locally delivering pro-coagulants. Our next step is to conduct preclinical tests toward developing a clinical trial for postpartum hemorrhage.

The project aims to produce a treatment for postpartum hemorrhage in order to save the lives of new mothers, and to contribute to broader prevention and treatment of hemorrhage and thrombosis.

BRIDGE-MTB: Bringing Integrated Data, Genomics, and Evaluation to Mycobacteria and Tuberculosis

Tuberculosis (TB) and non-tuberculous mycobacterial infections (NTMs) are bacterial infections that create serious problems in BC. Treating TB costs the health system nearly $13 million per year, and NTMs are emerging as a new and poorly-understood threat, especially in BC’s seniors.

My previous work has shown that we can get faster and cheaper information by replacing standard TB/NTM lab tests with a single genome sequence test on the bacteria. It has also shown that comparing the mutations in the genomes of bacteria from different patients allowed us to reconstruct the timeline of an outbreak, deducing who infected whom and when.

BRIDGE-MTB is a five-year province-wide program that will expand my previous work to explore three key areas:

If we use genomics to diagnose and phenotype every single mycobacterial isolate coming into our provincial lab, will it still prove better and faster than traditional laboratory methods? How will it improve our health delivery systems? How will it improve patient outcomes?
By looking for shared mutations in TB and NTM genomes, can we discover where, why and how TB and NTMs are spreading in BC? Can we use this technique of genomic epidemiology to control outbreaks?
The genomic data is complex. Can we design a clinical report that summarizes it in an intuitive, interpretable way for our doctors and nurses?

BRIDGE-MTB seeks to improve BC's practice and policy on testing, treating, controlling and understanding TB and NTMs.

Detecting neuroplasticity after spinal cord injury: Implications for neuropathic pain

Current interventions for neuropathic pain after spinal cord injury (SCI) have proven largely ineffective, an unfavorable outcome that can be partly attributed to poor understanding of mechanisms.

Through his research program, Dr. Kramer aims to shed light on this problem, focusing specifically on the hypothesis that changes in supraspinal (above the spine) structures contribute to neuropathic pain symptoms (e.g., burning sensation in the legs). In experiments using functional magnetic resonance imaging (MRI) and electroencephalography, a technique for measuring electrical activity in the brain, the brain activities following afferent stimulation in individuals with SCI will be investigated.

In an initial experiment, Dr. Kramer will explore how descending control of nociception, the neural processes of encoding and processing noxious stimuli, is affected by SCI. This will be done using behavioral manipulations to control awareness to noxious stimuli (e.g. placebo-analgesia, the inability to feel pain).

In the second experiment, Dr. Kramer will build on preliminary results, which indicate that neuropathic pain is associated with prominent changes in cortical functioning in brain areas involved in processing noxious stimuli. Beyond cortical functioning, he will also examine the role of plasticity in the brainstem in the maintenance of neuropathic pain.

In a final experiment, Dr. Kramer will delve further into the role of cortical and brainstem plasticity, determining the time course for when these changes occur. In proposed imaging experiments, the extent by which structural changes in the central nervous system accompany sensory deficits will be examined using quantitative anatomical MRI techniques.

As part of Dr. Kramer’s ongoing research program, quantitative approaches to objectively assess sensory function will continue to be developed. The focus of this work will be on validating novel neurophysiological and neuroimaging techniques to examine discrete elements of sensory impairments. Additionally, Dr. Kramer will continue to investigate the inter-relationship between neuropathic pain, other secondary complications (e.g., cardiovascular disease), and neurological recovery by analyzing large epidemiological SCI databases.

Overall, the research program will provide a clearer picture of the impact of neuropathic pain on neurological function, methods to improve objective measurement, and will enable implementation of novel interventions aimed at improving outcomes and quality of life for people with SCI.

Molecular detection of known and novel cancer predisposition genes

Diagnosis of inherited cancer susceptibility has implications for both the patient and their family, as certain drugs may be more effective in cancers caused by a patient’s inherited cancer risk. Carrier testing can also determine whether family members are at risk of cancer. Both the patient and at-risk family members may benefit from increased screening, surveillance and/or prophylactic cancer prevention measures. However, current gene-by-gene testing strategies are costly and time consuming.

To try to speed diagnosis, Dr. Schrader will use cutting-edge DNA sequencing technologies to identify the inherited basis of cancers that run in families or occur multiple times in a single individual. Dr. Schrader will also test the patient’s tumor DNA alongside their normal DNA to look for candidate genes altered in both samples that are most likely to be the basis of the patient’s inherited cancer.

As part of her five-year research program, Dr. Schrader also proposes using these same sequencing technologies to test whether we can improve upon current cancer detection strategies in individuals with known cancer susceptibilities. By screening body fluids for free DNA released from early tumors with secondary mutations, it may be possible to detect evidence of early tumors. A positive screen may alert physicians to undertake more targeted diagnostic strategies to find and treat cancers at an early stage. Furthermore, if these technologies are successful in detecting early cancer in these high-risk patient groups, similar strategies could also be considered for screening for common types of cancer in the general population. Finally, genome-wide sequencing also has the potential to reveal information regarding non-cancer related genetic disease risks. Arguably, the clinical uptake of genome-wide sequencing has been the fastest in oncology, where tumor sequencing is undertaken to identify drug-targetable mutations. Clinical and research practices regarding the management of potentially clinically significant incidental genomic findings are evolving. As a medical geneticist in the BC Cancer Agency, Dr. Schrader will research both the cancer and non-cancer related incidental findings revealed through the course of clinical and research tumor sequencing.

Understanding of the scope of potential incidental findings will be critical as the policy and practice moves forward with this regard.

Ion channels: Molecular determinants of health and disease in the head and heart

Though vastly different, both the brain and the heart rely on large complicated proteins called ion channels in order to function properly. These proteins facilitate the controlled flow of ions in and out of cells by forming pores that stud cellular membranes. Specialized brain cells called neurons utilize ion channels and the electrical signals they generate to communicate with one another. A repertoire of different ion channels also shapes the birth, growth and development of neurons. During brain injury, ion channel activity can render populations of neurons vulnerable to damage. However, following injury, ion channels can also sensitize surviving neurons and modify their structure and function in ways that allow them to respond, adapt and promote repair. Similarly, the electrical activity underlying the coordinated beating of heart muscle cells is generated by the concerted actions of a cohort of ion channels. It follows that mutations in the proteins that form ion channels can manifest in a spectrum of clinical neurological and heart conditions.

In a series of coordinated projects, Dr. Swayne is working to shed light on how ion channels impact on brain and heart health. Dr. Swayne has been examining the cell biology of pannexin ion channels and their role in neuronal development and injury-triggered plasticity. In collaboration with a group at the University of Ottawa, Dr. Swayne’s team is also studying how probenecid, a drug that stops the function of pannexins, impacts stroke recovery. In parallel, to identify novel ion channel regulators of developmental and injury-triggered neuronal plasticity, her lab is combining basic biochemistry with cutting edge expertise at the UVIC Genome BC Proteomics Centre. Finally, in partnership with the UBC Community Genetics Research Program, Dr. Swayne is also investigating the cell biological underpinnings of clinically relevant cardiac ion channel mutations affecting certain BC First Nations communities.

Overall, Dr. Swayne’s research will bridge critical knowledge gaps in the understanding of ion channel function and dysfunction in the brain and heart.