Vision loss from age-related macular degeneration (AMD) and other retinal degeneration diseases is due to the loss of the light sensitive photoreceptor cells in the eye. This is often secondary to dysfunction of the retinal pigment epithelium (RPE).
The photoreceptor and RPE cells are arranged in a characteristic mosaic. The mosaic is an accurate clue to how healthy these layers are. However, attempts to visualize these mosaics have been so far unsuccessful, despite technological advancements in conventional ophthalmic imaging.
Dr. Ju will develop a novel clinical ophthalmic imaging system to visualize and quantify the changes of the structure and function of photoreceptor and RPE cells in humans. The results of this research will provide a clearer understanding of the pathological processes of AMD, which will help clinicians establish more reliable clinical treatment options.
Dr. Bean will explore women’s experiences throughout their participation in the Small Steps for Big Changes lifestyle counseling program, a community-based exercise intervention for individuals who are living with prediabetes. Interviews with participating women will provide an understanding of women’s attitudes, beliefs, experiences and behaviours related to engaging in a lifestyle community program, in order to best understand the facilitators and barriers to intervention engagement and completion, as well as exercise adherence over the course of one year.
Women who have been diagnosed as prediabetic but do not have access to a community-based intervention will be interviewed in order to also understand these women’s attitudes, beliefs, experiences and behaviours over the course of the same year. This will help understand the influences and impacts of the intervention program, as well as understand if there is a need for more resources for these prediabetic women.
Dr. Bean’s research will address several gaps in the current literature, including adopting a qualitative and longitudinal approach and attaining an in-depth understanding of the efficacy of community-based exercise interventions specifically for women. Her findings will be adapted into community learning sessions, which will provide an opportunity for a community of practice to develop for women involved in this study in which they can learn from each other’s experiences.
Children with attention-deficit/hyperactivity disorder (ADHD) have trouble sustaining attention and may also display excessive hyperactivity and impulsivity. A major day-to-day impairment for children with ADHD is in their social relationships with peers. In this area, children with ADHD frequently struggle, and have trouble making and keeping friends as a result. It is important to address these issues early, as social problems increase children’s risk for many negative outcomes including academic failure, aggression and delinquency, substance abuse, and depression and suicide.
Research suggests that difficulties with executive functions (e.g., attention, self-control, working memory, organization and planning) are a key part of ADHD. However, it is not yet clear how executive functioning difficulties may affect the problems children with ADHD face in their daily life, such as peer relationships.
Dr. Hudec will explore how executive functions relate to social skills and the ability to make and keep friends in children with ADHD. This will lead to a better understanding of the social problems affecting children with ADHD.
Importantly, symptoms of ADHD frequently occur within families, so parents of children with ADHD are more likely to experience ADHD themselves, and to be at risk for poor executive functioning themselves. Dr. Hudec will also examine how parental executive functioning may affect parents’ ability to implement behavioural interventions.
Understanding how executive functioning in both children and adults affects children’s social problems may help improve available clinical treatments for children with ADHD and will guide development of therapeutic activities that can be adapted to parents’ strengths and weaknesses. Dr. Hudec’s findings will be shared through family-based interventions and community-based education sessions, as well as professional presentations and publications that will inform practice by researchers and clinicians.
Drug treatments are essential for the survival of cancer patients. Unfortunately, medications needed for treatment can also cause permanent disabling side effects, severely impacting on the quality of life of patients already suffering the devastating consequences of cancer.
Although platinum-based drugs such as cisplatin are highly effective and are the most frequently used class of cancer medications, they are also accompanied by severe side effects. In fact, up to 80% of patients treated with cisplatin lose some ability to hear and/or experience kidney injury.
If clinicians were able to predict which patients are most likely to experience these side effects before prescribing cisplatin, they could take measures to avoid their occurrence. Pharmacogenomics, the study of how genetic differences influence why we respond differently to medications, aims to provide clinicians with this predictive information.
Dr. Drogemoller will investigate patients receiving cisplatin to identify the genetic and clinical variables that are associated with high risk of kidney failure and hearing loss. She will use these results to guide the development of predictive tests and novel treatment strategies. The results of this research will allow for the implementation of personalized treatment strategies which optimize benefits and reduce the chance of harm for cancer patients.
The complex microbial ecosystem inhabiting the distal human gut, known as the gut microbiota, is inextricably linked to human health, playing central roles in maintaining host immunity, safeguarding the host against pathogens, and extracting energy from the otherwise indigestible complex carbohydrates found in dietary fibre.
Dysbiosis, an imbalance in the gut microbiota, is linked to a range of diseases, including inflammatory bowel diseases, metabolic syndrome, and Type 2 Diabetes. A growing body of evidence supports a role for microbial therapeutics, such as commercially available probiotics, in mitigating the effects of some dysbiosis-associated conditions. However, the implementation of novel, customizable therapeutics depends on the establishment of a comprehensive repository of species with known energetic requirements and ecological behaviours.
Currently we lack atomic-resolution insight into the molecular machinery required for complex carbohydrate utilization by key gut symbionts. Understanding this machinery is critical to understanding the role of carbohydrate utilization in shaping microbial communities in the human gut.
Dr. Grondin will employ structural biology in a systems-based approach, incorporating complimentary bacterial genetics and carbohydrate biochemistry to determine the atomic structures of transport protein machinery in complex with the related substrates. Comparative structure-function studies of carbohydrate-transporters, including measuring transport specificity and kinetics across substrate type and bacterial phylogeny, will delineate the role of individual complexes in fuelling microbial ecosystems. This research will provide detailed insights into the molecular mechanisms associated with the selective recognition, transport and metabolism of complex carbohydrates by the human gut microbiota. The results of will inform the development of therapeutics to address growing health concerns associated with microbiotal imbalance, such as inflammatory bowel diseases, metabolic syndrome, and Type 2 Diabetes.
Gay, lesbian and bisexual (GLB) Canadians are at higher risk of depression, anxiety, drug and alcohol use problems and suicide attempts, but there are few places where these mental health needs can be met in a way that is mindful of the judgment GLB people may fear on the basis of their sexuality. Many sexual health clinics already serve as GLB-sensitive points of care for diagnosing and treating sexually transmitted infections, including HIV. These clinics and their nursing staff could be supported in routinely offering assessment, referral, and counseling for mental health concerns; however, the extent to which this is needed and desired has not yet been explored. Dr. Salway will use a combination of data sources and methods to characterize the potential for such interventions.
This study will answer three questions:
- What are the unmet mental health service needs of GLB clients of sexual health clinics?
- How can these needs potentially be met through the sexual health clinics?
- What is the appeal of new approaches to meeting mental health needs through sexual health clinics?
Dr. Salway will use a large, linked data set to estimate how many sexual health clinic clients currently access mental health-related services from other hospitals or clinics. Interviews will be conducted with nurses and clients, and a survey will be administered at three sexual health clinics in Vancouver that predominantly serve GLB populations.
Dr. Salway’s research will be conducted in collaboration with nurses, clinic managers, and policy-makers to ensure that results are applied to existing services. Through these collaborations, findings will be translated into clinical guidelines, training programs for clinicians, and policy recommendations. Ultimately, this study will provide evidence for promising strategies that will not only improve health care for sexual health clinic clients, but also contribute to reductions in mental health disparities that continue to affect GLB Canadians today.
Recently, loss-of-function mutations of the GBA1 gene, which encodes glucocerebrosidase (GCase), have been characterized as a major genetic risk for Parkinson’s disease (PD). Patients carrying these mutations have a much higher incidence of PD, earlier onset, and more severe disease.
These data strongly suggest that GCase activity may be useful for early diagnosis as well as monitoring the progression of PD. Dr. Gros will build on her previous work describing a substrate that specifically measures GCase activity both in vitro and in neuronal cells in microscopy. This research will lead into a proof-of-concept clinical study, using a flow cytometry assay to establish correlations between the progression of PD, GBA1 mutant status and GCase activity.
The results of this study will lead to the development of a new assay for clinical studies that will benefit Parkinson’s patients and deepen our overall understanding of the disease.
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.
Spinal cord injury (SCI) resulting from traumatic accidents is one of the most debilitating chronic conditions. In addition to the toll on quality of life, lifetime health care expenditures for these patients are among the most expensive of any medical condition, since many injuries occur in young patients who live with SCI for decades. SCI also comes with steep indirect costs, including morbidity due to chronic complications.
In individuals with SCI, bladder dysfunction and episodes of high blood pressure are two chronic conditions that present as significant clinical problems. Bladder dysfunction is commonly associated with a sudden, life threatening increase in blood pressure known as autonomic dysreflexia (AD). This episodic hypertension cannot be addressed with typical treatments, and if misdiagnosed or poorly managed can lead to myocardial infarction, stroke, and even death. Bladder dysfunctions and irritation such as a urinary tract infection are leading triggers for AD.
It is suspected that chronic exposure to AD episodes results in cerebrovascular damage in those with SCI. Chronically elevated blood pressure negatively impacts the brain and is specifically associated with cerebrovascular decline, altered brain morphology, cognitive dysfunctions and stroke in able-bodied individuals. However, identical pathologies are present in those with SCI.
Dr. Walter will investigate whether treating bladder dysfunction in patients with SCI will decrease possible triggers for episodes of AD, ameliorate its symptoms and consequently reduce chronic cardiovascular complications. Reducing the chronic cardio- and cerebrovascular complications of SCI would dramatically improve the health and wellbeing of patients with SCI and positively impact health care costs.
One in eight men in Canada will be diagnosed with prostate cancer in their lifetime. Despite the availability of surgical, radiological and drug treatment options, many patients develop castration resistant prostate cancer (CRPC), an incurable disease which is especially resistant to drugs. In its most lethal form, drug resistant CRPC behaves like a neuroendocrine cancer, which is completely unresponsive to traditional prostate cancer therapies.
In his model of drug resistant CRPC, Dr. Munuganti has identified a molecular pathway that appears to be essential for prostate cancer to take on neuroendocrine features. A key protein in this pathway, BRN2, is high in patients with neuroendocrine prostate cancer and is critical for neuroendocrine tumour growth in a laboratory model. BRN2 expression also plays a critical role in other neuroendocrine cancers such as small cell lung cancer and Ewing sarcoma. There is an urgent need to develop drugs that have the ability to inhibit the function of BRN2 for the treatment of patients with deadly neuroendocrine tumors.
Using high-powered and intelligently designed computer models, Dr. Munuganti has developed drug prototypes that have the ability to prevent BRN2 from supporting neuroendocrine cancer cell growth in our laboratory models. Dr. Munuganti’s study will fine-tune the drug-like properties of the leading BRN2 inhibitors and test them in biological models of neuroendocrine cancers. The results of this research could lead to the development of new therapies capable of reducing or slowing the growth of lethal neuroendocrine cancers, substantially improving patient survival.
Findings will be presented at conferences and seminars such as AACR Annual Meetings and the ASCO Annual Meeting, providing an opportunity to exchange ideas with other researchers and clinicians in the field and opening up possible collaborations. The ultimate goal of this study will be to commercialize a BRN2 inhibitor for patients suffering from no-cure neuroendocrine tumours.
