Research Location: University of Victoria

Evaluation of the role of FRMP on BDNF expression and signaling

Fragile-X syndrome (FXS) is the most common form of inherited intellectual disability and is the best characterized form of autism spectrum disorder. This genetic condition is caused by a mutation in the FMR1 gene, leading to the functional loss of FMR1 protein (FMRP). Besides being important for neuronal development, this protein also exerts a strong influence on synaptic plasticity. As a matter of fact, FMRP is highly expressed in the dentate gyrus (DG) of the hippocampus, one of the few regions of the adult brain where the birth of new neurons takes place. 

To understand this relationship, it is important to clarify the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of FXS. BDNF is an important regulator of neural circuit development and function, and is thus strongly implicated in the development and treatment of several neurological conditions. Interestingly, it has been shown that BDNF and FMRP may reciprocally regulate each other.

However, BDNF is a complex signaling molecule, and its pro- and mature forms can elicit opposing biological effects. Thus, to fully understand the interaction between FMRP and BDNF it is important to study both its pro- and mature forms. Dr. Bettio will investigate how FMRP regulates BDNF/pro-BDNF expression in distinct brain regions and how changes in BDNF expression contribute to hippocampal circuit dysfunction and plasticity defects in FXS. 

The results of this study will expand scientific knowledge about the molecular mechanisms implicated in FXS, and will be key in the development of future BDNF-based therapeutic strategies.

 

Addressing HIV/AIDS, sexual health, and substance use among gay and other men who have sex with men

New HIV diagnoses are 71 times higher among gay, bisexual and other men who have sex with men (GBM) than other men in Canada. Since 2010, BC has adopted Treatment as Prevention (TasP) as a policy to increase HIV testing and engage more HIV-positive individuals in effective treatment to reduce transmission at a population level. However, the number of new diagnoses among GBM in BC has remained largely unchanged. Further, surveillance shows an increase of HIV diagnoses among the youngest birth cohorts of GBM. HIV pre-exposure prophylaxis (PrEP) is a new preventive tool for HIV-negative GBM, but inaccurate information, sub-optimal adherence or risk-compensation could result in a false sense of security, paradoxically leading to increased HIV transmission. In addition to HIV, infectious syphilis is now epidemic among GBM in BC.

This research program will address the HIV and sexually transmitted infection (STI) epidemics among GBM in Metro Vancouver and BC. Dr. Lachowsky will measure HIV risk behaviour over time, determine how PrEP affects bacterial STI incidence, and analyze shifting attitudes about HIV, challenges with HIV prevention and treatment, and changes in sexual negotiation and practices. Results will directly inform population-specific, age-relevant public health policy, programming, and interventions to reduce the burden of HIV for GBM, especially young GBM.

Dr. Lachowsky will employ a bidirectional, integrated knowledge translation approach, with a Community Engagement Committee and key academic, public health, and community partners. An interactive Web 2.0 hub will allow for knowledge dissemination and generation with community and service providers, and will be complemented with more traditional presentations, workshops, and publications.This single research project is part of a larger program of research examining health disparities amongst GBM in BC and Canada using interdisciplinary, community-based approaches.

The Effect of Psychosocial Stressors on Health Behaviours and Indicators of Cardiometabolic Risk in the Transition to Young Adulthood

Adolescence and young adulthood are critical periods for health promotion and disease prevention. Cardiometabolic risk (CMR) refers to a set of indicators that increase an individual’s risk for diabetes, heart disease or stroke. These indicators start to show predictive variability in adolescence and identification and implementation of early strategies for risk management can have significant long-term health benefits. Much of what we know about CMR comes from studies of adults; therefore, research focusing on earlier age groups is needed.

The first objective of the proposed research is to describe the frequencies of select, non-invasive CMR indicators, including body mass index (BMI), systolic and diastolic blood pressure (BP), and waist circumference in young adulthood (ages 22-29). Research in psychoneuroimmunology documents the deleterious effects of stress on physical health; however, less attention has been given to adolescents and young adults.

The second objective is to examine how psychosocial stressors that become salient in adolescence (e.g. internalizing symptoms and interpersonal stress) predict CMR.

The third objective is to examine how these stressors compromise the enactment of key health behaviours (e.g. physical activity, eating habits, sleep duration) leading to increased CMR.

The project will use six waves of the Victoria Healthy Youth Survey (V-HYS), a 10-year longitudinal study that surveyed youth (N = 662) biannually from 2003 (T1; ages 12-18) to 2014 (T6; ages 22-29). In-person measurements of CMR (BMI, systolic and diastolic BP, waist circumference) were collected at T6. Measurements of internalizing symptoms, interpersonal stress (e.g. peer victimization), and health behaviours were collected at each wave.

Findings will highlight the variability in CMR in young adulthood and increase knowledge on the effects of two salient stressors on CMR from adolescence to young adulthood, providing new information about targets for prevention and interventions. The results will also inform guidelines for early identification and preventative healthcare.

Knowledge translation efforts will include 1) peer-reviewed publications, conference presentations, media reports, and policy formats; 2) creating an infographic about CMR in young adulthood to release to the media; and 3) developing a training tool to educate healthcare professionals about the relations between stress and CMR in these young age groups.

Improving health equity through cross-cultural collaboration: Learning from Indigenous-developed programs to strengthen public health systems in preventing the harms of substance use in BC

A function of public health systems and services is to reduce health inequities. The harms of substance use impact British Columbians differently based on their social position and access to resources. Over the last decade, BC has had renewed interest in health equity as demonstrated by several key policy documents. Initial research findings however, have demonstrated that the application of a health equity lens is a challenge for public health decision makers and practitioners. However, for many public health service providers, First Nations and Aboriginal health organizations and service providers are seen as leaders in the understanding and application of health equity principles.

Accordingly, there is an immense opportunity in BC for collaboration and learning with First Nations and Aboriginal health partners to optimize health equity for all British Columbians. Despite these opportunities, little is known about the synergies between Indigenous knowledge and health equity strategies related to the reduction of harms of substance use in BC. In particular, more research is needed to understand if Indigenous approaches to health and wellness can be imported into the current BC public health system and to  explore how Indigenous-developed programs and services can inform health equity strategies related to reducing the harms of substance use in BC public health systems and services.

This research project will be one of the first to systematically examine how health equity strategies in the BC public health system could benefit from Indigenous knowledge and worldviews. This project has the potential to impact the health of all British Columbians by informing the development of more equitable health programs and services. In addition, by prioritizing Indigenous ontologies and processes, this project also has implications for how Aboriginal communities in BC are perceived and esteemed, thereby having the potential also to specifically improve the well-being of those communities. In addition, this prioritization has the potential to mitigate epistemological colonialism and shift power relations which are integral in promoting health equity for Indigenous peoples.

Dr. Shahram received a 2017 Health Policy Fellowship to promote Indigenous health in BC’s southern interior by integrating cultural safety and health equity assessments into the fabric of the Interior Health. Her 2016 Trainee Award will placed on hold during her health policy fellowship assignment.

Mechanisms of impaired functional recovery in diabetic mice following stroke

Diabetics are two to four times more likely than non-diabetics to suffer a stroke during their lifetime, and their prognosis for recovery from stroke is poor. Diabetes is known to negatively affect blood vessels throughout the body, including the eye, heart, kidney, and limbs, leading to a heightened risk of stroke in diabetics. Poor circulation and peripheral nerve damage can lead to blindness, hearing loss, foot injury and amputation. High blood pressure is common in diabetics and increases the risk of heart disease and stroke. However, little is known about how the vascular changes associated with diabetes affect the brain and contribute to poorer recovery of function following stroke.

Dr. Kelly Tennant's research will determine why diabetics suffer from greater impairments following strokes. She will monitor changes in neurons and blood vessels over time following a stroke in diabetic mice and assess the relationship between these changes and recovered use of the forelimb. Dr. Tennant will employ cutting edge in vivo imaging technologies such as intrinsic optical signal, two-photon, and voltage sensitive dye imaging, combined with behavioural testing of forelimb function.

These experiments will shed light on how neurons and blood vessels of diabetics respond differently to ischemic stroke and how these differences contribute to poor behavioural recovery in diabetic stroke survivors. This research will aid understanding of the greater impairment caused by stroke in diabetic patients and lead towards development of treatments that ameliorate the negative effects of diabetes on the brain.

Mitigation of hippocampal dysfunction and cognitive deficits in early-symptomatic YAC128 transgenic mice for Huntington’s disease

Huntington's disease is a devastating neurodegenerative disorder affecting between three and 10 individuals per 100,000 in the Western world. It is caused by a mutation in the huntingtin gene, which results in the accumulation of mutated huntingtin protein in the brain and the eventual degeneration of certain types of brain cells. The disease is primarily characterized by the onset of motor deficits; this develops when the striatum region deep within the brain begins to degenerate. However, Huntington’s disease patients commonly show cognitive impairments decades before the onset of the motor symptoms. The hippocampus is a brain region known to be involved both in cognitive (i.e. learning and memory) and emotional (i.e. depression) processes.

Dr. Joana Gil-Mohapel is investigating whether the hippocampus is involved in the early cognitive impairments in Huntington’s disease. She is working with a mouse model of Huntington’s disease, which closely mimics the human condition. These mice demonstrate profound structural and functional deficits in this region; significantly, as seen in Huntington’s disease patients, these deficits can be detected when the animals are still in an early-symptomatic stage, before the onset of motor symptoms. Therefore, the goal of the present research is to gain a better understanding of how this structure is affected in this mouse model.

Dr. Gil-Mohapel will investigate whether relevant cellular pathways are altered in this brain region and whether therapies aimed at promoting hippocampal function can reverse these deficits and be of therapeutic value for Huntington’s disease. She hopes her research will help elucidate novel targets for the mitigation of the cognitive deficits characteristic of early-stage Huntington’s disease patients.

Treatment of drug-resistant influenza: Rationally designed inhibitors of viral neuraminidase

Each year the influenza virus infects approximately 10% of the human population, resulting in hundreds of thousands of deaths. Even in North America, nearly 40,000 annual “excess deaths” are attributed to influenza or to secondary bacterial infections. Despite a World Health Organization-monitored vaccine program, the disease remains a significant global health issue, requiring the use of antiviral drugs like oseltamivir (Tamiflu). A significant problem in controlling the spread of influenza is the emergence of oseltamivir-resistant strains.

To address this problem, Dr. Jeremy Wulff is taking a collaborative approach to develop potent new influenza virus inhibitors. With Professor Martin Boulanger's group at the University of Victoria Department of Biochemistry, Dr. Wulff has developed a new class of antiviral agents that function by a similar mechanism to oseltamivir. His research group is working to further improve the efficacy of these agents through structural and kinetic means. Finally, Dr. Wulff will test the potency of the new anti-influenza compounds in collaboration with Dr. Terrence Tumpey, from the U.S. Centers for Disease Control in Atlanta.

Identifying and developing new drugs to fight oseltamivir-resistant influenza is anticipated to have wide-reaching impacts on global health. In addition to creation of new influenza drugs, Dr. Wulff’s research interests include the development of novel methodologies for the synthesis of complex molecules, and the invention of new kinds of inhibitors that specifically block interactions between certain proteins involved in pancreatic cancer and HIV.

Impacts of a Palliative Approach for Nursing (IPAN)

This practice-relevant nursing health services research initiative will address the questions:

  1. How and in which contexts can a palliative approach better meet the needs of patients with a life-limiting illness and their family members?
  2. How can a palliative approach guide the development of innovations in health care delivery systems to better support nursing practice and the health system in British Columbia?

Continue reading “Impacts of a Palliative Approach for Nursing (IPAN)”

Evaluation of the Integration of Nurse Practitioners into the BC Healthcare System

The nurse practitioner (NP) role is new to BC and its impact has yet to be evaluated. The proposed multi-year study will evaluate a practice innovation – the integration of NPs into the BC healthcare system, and will establish a framework for sustainable ongoing evaluation of the impact of NP practice on those they serve and the health care system. The study process will be divided into three parts addressing the following broad questions:

  1. What changes result for patients, and what are the implications for the health care system when NPs become part of the care process?
  2. What is the impact of adding a NP to the functioning of collaborative health care teams?
  3. What are the practice settings and scope of practice of NPs working in BC?

The final work of the project team will be to use the study findings to develop an ongoing evaluation method for future data collection and evaluation of NPs’ practice and impact.

Evaluation of the Residential Program Care Delivery Model

CDM was launched in Fraser Health in July 2010, with plans to implement the model across all residential care beds in the Health Authority. The model consists of three inter-related aspects: staff mix, funding methodology and direct care hours. CDM sets a goal of reaching 3.36 direct care hours per resident per day across Fraser Health by targeting residents, their families and staff in residential care programs in FH-operated facilities. The evaluation project will examine Phase 1 of the implementation of CDM (July 2010 to January 2011) and will include monitoring funding indicators as well as quality of care indicators.