Biomedical

Predictors of immunotherapy benefit in patients with microsatellite stable metastatic colorectal cancer

Introduction: Colorectal cancer (CRC) is the second most common cancer. Once metastatic, patients are generally incurable and receive treatment to prolong survival. Immunotherapies use a patient's immune system to attack their cancer. These treatments are effective in CRC patients with microsatellite instability (MSI). Unfortunately, 95% of patients lack MSI and are called microsatellite stable (MSS). This group usually doesn't respond to immunotherapy and we need to explore why.

Specific Aims:  

We aim to identify:

Primary Investigator: 
Year: 
2019

New strategies for unclogging microcirculatory obstructions in the healthy and diabetic brain

Recent work from our laboratory has shown that the brain capillaries routinely get 'stuck,' clogged by cells and debris even under healthy conditions. Most of these clogged capillaries clear within seconds to minutes, however, some can remain stuck for much longer. We also reported that about one third of these clogged capillaries were eliminated from the blood vessel network and never get replaced. Importantly, there are certain conditions which can increase the risk of clogged blood vessels in the brain such as diabetes.

Primary Investigator: 
Award Type: 
Year: 
2019

Structural basis of novel strategies for the inhibition of AmpC-mediated beta-lactam antibiotic resistance in the opportunistic, nosocomial pathogen Pseudomonas aeruginosa

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen often responsible for hospital-acquired infections, which can be very difficult to treat due to antibiotic resistance. A common mechanism of resistance is the expression of beta-lactamase enzymes, which break down and disarm classical beta-lactam antibiotics, such as penicillins. Beta-lactam antibiotics act by breaking down the bacterial cell wall, producing cell wall fragments that induce expression of the beta-lactamase, AmpC.

Primary Investigator: 
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Year: 
2019

Investigating components of a Campylobacter jejuni iron uptake system to inform antimicrobial strategies.

Campylobacteriosis is an infectious diarrheal disease and one of the largest contributors to hospitalizations and deaths from food poisoning in Canada and worldwide. It is usually caused by consumption of food or water contaminated by the bacterium Campylobacter jejuni, resulting in watery or bloody diarrhea, fever, and serious post-infectious illnesses. This illness is especially dangerous for very young or old people, made worse by lack of a vaccine and increasing frequency of infections that are resistant to treatment by current antibiotics. A recent WHO report identified C.

Primary Investigator: 
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Year: 
2019

Engineering stem cells to improve adaptive immune function

Thousands of Canadians receive bone marrow transplants each year to treat cancer and immune disease. Unfortunately, not only is this treatment dangerous, it is only effective for a small subset of cancers and immune disorders. Our goal is to provide a safer alternative to marrow transplantation that can be applied to a broad set of indications.

Primary Investigator: 
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2019

Generation of fully mature, functional islet-like organoids from human pluripotent stem cells in vitro

Insulin is a hormone that is crucial for maintaining normal blood sugar levels and is produced by beta-cells in the pancreas. If the amount of beta-cells is insufficient, or beta-cells stop making insulin, blood sugar levels start to rise which can lead to diabetes. Islet transplantation can supply the necessary amount of beta-cells and achieve superior glucose control over exogenous insulin injection, but is extremely limited by its reliance on organ donations. As a result, only a small fraction of people afflicted with diabetes currently benefit from these cell replacement therapies.

Primary Investigator: 
Award Type: 
Year: 
2019

Uncovering how specific "STAC" proteins regulate muscle contraction

Skeletal and heart muscle contraction requires calcium ions. Calcium ions enter muscle cells through 'calcium channels', which are effectively gates comprised of protein. The exact timing of the opening and closing of these gates is critical for normal muscle function, whether in maintaining a regular heartbeat or in enabling physical movement of the body as a whole. Any deviation in these calcium channels can cause calcium excess, which may result in disease. These include inherited cardiac arrhythmias or muscular disorders (e.g. Native American myopathy).

Award Type: 
Year: 
2019

Small molecules for bad bacteria: Novel peptidomimetics to battle resilient clinical infections

The lack of effective antibiotics in cases such as surgeries, transplantations, early-term and complicated births, sepsis etc. could merely lead to death as antibiotics are crucially needed for treatment. Sepsis for instance, annually kills ~8 million people worldwide with almost 40% of all deaths are linked to antibiotic failure. Likewise, infections caused by bacterial biofilms represent ~65% of all clinical diseases, and there are no antibiotics to treat bacterial biofilms, specifically.

Primary Investigator: 
Award Type: 
Year: 
2019

Studying motion processing with eye movements in healthy older adults and patients with ophthalmic diseases

As our population ages, an increasing number of Canadians experience difficulties with their vision. Although it is well known that both normal aging and age-related eye disease can affect a person's ability to see fine detail (such as in reading), tests of visual acuity used in regular eye examinations do not provide a complete picture of a person's ability to see in everyday situations, such as exercising and driving, where moving objects are often involved.

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Year: 
2019

When poor construction leads to destruction: How do structural defects in the light-sensing cells of the eye cause blindness?

Retinal degenerative disorders are inherited diseases that affect tens of thousands of Canadians. The effects are devastating; severe vision loss or complete blindness occurs early in life, resulting in the loss of livelihood, mobility, and independence. There is no cure, and present treatments focus on easing the symptoms of blindness instead of preventing vision loss in the first place.

Primary Investigator: 
Award Type: 
Year: 
2019

Role of TAK1 in resident fibro/adipogenic progenitors. A Key modulator of the inflammatory milieu and a therapeuthic target in chronic diseases

In our aging society, degenerative complications of chronic diseases are on the rise and account for a significant percentage of deaths. Among these, fibrosis is the most common, and yet no therapy capable of mitigating its effects is available. Investigating and understanding the signaling pathways that influence fibrogenic progenitor (FAP) fate will not only elucidate a key component of the regenerative process but may reveal pathways that could be targeted therapeutically to prevent inflammation, fibrosis, and enhance regeneration or maintain muscle homeostasis.

Primary Investigator: 
Award Type: 
Year: 
2019

Generating tissue capable of forming blood-progenitor cells at clinical scales

Chronic diseases consume 67% of direct healthcare costs in Canada. Regenerative medicine (RM) is a powerful strategy to address chronic diseases. The next generation of RM therapeutics targets development of living cells and tissues to treat specific indications. Availability of stable progenitor stem cell bio-banks that can be differentiated to desired phenotypes is a crucial pre-requisite.

Primary Investigator: 
Award Type: 
Year: 
2019

Non-invasive Neuroprosthesis for Cardiovascular Recovery Following Spinal Cord Injury

Spinal cord injury (SCI) not just causes paralysis but also more devastating issues such as impaired blood pressure (BP) and heart rate regulation, which are among the leading causes of illness and death among this population. The individuals with SCI above the mid-thoracic level commonly suffer from highly labile BP that rapidly reaches alarmingly high and low levels within the same day. These extreme BP fluctuations often result in seizures, ruptured brain blood vessels and even death.

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2019

Investigating the Role of MicroRNAs on Granule Cell Development during Mouse Cerebellar Development

The cerebellum is a complex region of our brain involved in the coordination of our movements and cognition. Evidence shows that cerebellum is involved in several brain disorders such as ataxia (inability to move properly), autism, and medulloblastoma (the most prevalent brain tumor in children). The cerebellum is made of different cell types. Among them, the most numerous cell type, the granule cells, contribute to many crucial cerebellar functions. Indeed, an uncontrolled division of granule cells results in the most common form of pediatric brain tumor, the medulloblastoma.

Primary Investigator: 
Award Type: 
Year: 
2019

Assessing Small Airway Disease Heterogeneity in Asthma to Identify Novel Therapeutic Targets

Asthma is a serious public health issue in Canada and in the world, affecting more than 300 million people globally. To date, clinical trials have established that current treatment strategies for asthma can relieve patient symptoms, but none are able to reverse the disease process. It is known that in asthmatic lungs, the airways -tubes that allow air to flow in and out of the lungs for breathing - are continually injured and scarred in a process called fibrosis.

Primary Investigator: 
Award Type: 
Year: 
2019

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