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Improving whole-genome sequencing as a clinical test for intellectual disability

Intellectual disability (ID) is a life-long affliction that impairs the cognitive functioning and adaptive behavior of affected individuals. About two to three percent of people worldwide suffer from ID. ID is mostly caused by irregularities in the DNA of an individual and is the most common reason for genetic testing. There are thousands of different mutations that we now know can cause ID. Diagnosis is necessary for accurate and effective genetic counselling, however deciphering the underlying genetic component remains a challenge.

Primary Investigator: 
Award Type: 
Year: 
2017

Elucidating the effect of O-GlcNAc modification on protein stability

The glycosylation of proteins with O-GlcNAc is a ubiquitous post-translational modification found throughout the metazoans. Deregulation of O-GlcNAcylation is implicated in several human diseases including type II diabetes, Alzheimer’s disease, and cancer.

However, the basic biochemical roles of O-GlcNAcylation remain largely unanswered. Several recent studies have demonstrated a clear link between O-GlcNAc and cellular thermotolerance.

Primary Investigator: 
Award Type: 
Year: 
2017

Development of improved substrates for live cell imaging to aid in discovering new glucocerebrosidase therapeutic agents

Parkinson’s disease (PD) is a neurodegenerative disorder that affects millions of people worldwide, with no standard treatment currently available. Therefore, there is a major need for new therapeutic agents to treat or prevent the progression of PD. One promising solution involves targeting the protein glucocerebrosidase (GCase) encoded by the gene GBA1. Studies have shown small molecules that increase GCase activity could help prevent the progression of PD.

Primary Investigator: 
Award Type: 
Year: 
2017

The acute impact of spinal cord injury on cardiac function, and novel hemodynamic management in SCI patients

Following acute spinal cord injury (SCI), one of the only presently available neuroprotective strategies is to try and optimize management of spinal cord blood flow. This treatment specifically aims to immediately increase blood flow to the injured spinal cord tissue to prevent the spread of injury to surrounding spinal cord tissues.

Primary Investigator: 
Award Type: 
Year: 
2017

The role of PCSK9 in clearance of bacterial lipids and the development of anti-PCSK9 treatment for sepsis

Sepsis, which is characterized as an uncontrolled inflammatory response to severe infection, is the leading cause of death in intensive care units. In Canada, sepsis led to a total of 13,500 deaths in 2011, which translates to approximately one in 18 deaths in Canada involving sepsis. Despite this pressing medical need, there are currently no effective treatments for sepsis. 

Primary Investigator: 
Award Type: 
Year: 
2017

Evolutionary determinants of treatment resistant high grade serous ovarian cancer investigated at single cell resolution

Women diagnosed with high grade serous ovarian cancer (HGS) continue to face poor prognosis, with ten-year survival at only 30-40%. Surgical cytoreduction followed by platinum and taxane-based chemotherapy result in clinical remission for a majority of patients. However, up to 80% of patients will suffer relapse because their disease is treatment resistant. Improved outcomes for HGS require both biomarkers of treatment resistance and development of additional treatments targeting tumour cells resistant to first line therapies.

Primary Investigator: 
Award Type: 
Year: 
2017

The real-world effectiveness of hepatitis C virus (HCV) treatment on decompensated cirrhosis and hospitalizations

Between 230,000 to 450,000 Canadians are infected with hepatitis C virus (HCV). Most of these people were infected decades ago and remained untreated due to the severe side effects and low effectiveness of interferon-based treatment regimens. Therefore, HCV associated liver related morbidity and mortality are now on the rise, with substantial impact on health care utilization. 

Primary Investigator: 
Award Type: 
Year: 
2017

The role of material security in improving health for people who use illicit drugs

It is well known that an adequate and secure income promotes health. However, material security (e.g., housing, food, and service access) may operate distinctly from income security, particularly for people who use illicit drugs, whose ongoing need to acquire drugs may affect the degree to which income security translates into material security and subsequent health improvements. Nevertheless, material security and its relationship with health are not well understood, an important oversight in research among people who use illicit drugs (PWUD). 

Primary Investigator: 
Award Type: 
Year: 
2017

Targeting stress granules: A novel strategy to inhibit Ewing sarcoma metastasis

Metastatic disease remains the single most powerful predictor of adverse outcomes in Ewing sarcoma (ES) and other childhood sarcomas (malignant connective tissue tumours). High risk ES appears to be characterized by uninhibited outgrowth of neoplastic clones that have acquired additional genomic or epigenomic alterations, which facilitate the spread of the cancer cells. 

Primary Investigator: 
Award Type: 
Year: 
2017
Health Category: 

In vivo multi-resolution functional optical imaging for investigation of age-related macular degeneration (AMD) process

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. 

Primary Investigator: 
Award Type: 
Year: 
2017

Exploring women’s experiences in a prediabetes community-based exercise intervention

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. 

Primary Investigator: 
Award Type: 
Year: 
2017

Role of executive functions in parenting behaviours and children’s social functioning in families of children with ADHD

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.

Award Type: 
Year: 
2017

Unraveling the genetics of severe reactions to chemotherapy: Moving towards maximum benefit with minimal harm

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.

Primary Investigator: 
Award Type: 
Year: 
2017

Molecular mechanisms of complex carbohydrate uptake by human gut microbiota

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. 

Primary Investigator: 
Award Type: 
Year: 
2017

Can specialized sexual health clinics address unmet mental health needs of sexual minorities?

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.

Primary Investigator: 
Award Type: 
Year: 
2017

Development of a flow cytometry assay for accurate and selective measurement of lysosomal GBA1 activity in PBMC

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. 

Primary Investigator: 
Award Type: 
Year: 
2017

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. 

Primary Investigator: 
Award Type: 
Year: 
2017

Impact of treatment for neurogenic bladder dysfunction on autonomic dysreflexia and cerebral blood flow in SCI individuals

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. 

Primary Investigator: 
Award Type: 
Year: 
2017

Targeting neural transcription factor BRN2 in neuroendocrine tumours

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. 

Primary Investigator: 
Award Type: 
Year: 
2017
Health Category: 

The maladaptive effects of wood smoke on abdominal aortic aneurysms

Cardiovascular disease is the leading cause of death worldwide. Approximately 80% of all aneurysms that form within the aorta (the major blood vessel that deliveries oxygenated blood to the body) occur in the abdominal region. These are classified as abdominal aortic aneurysms (AAA). AAA is associated with progressive weakening and, ultimately, rupture of the vessel wall, causing rapid and extreme blood loss and a high rate of mortality. Sadly, aneurysm rupture is often the first sign of the disease and many die before reaching a hospital.

Primary Investigator: 
Award Type: 
Year: 
2017
Health Category: 

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