Despite being hampered by painful injuries, many athletes continue to compete and win. For example, Toronto Maple Leafs defenceman Bobby Baun played several playoff games with a broken ankle and helped his team win the Stanley Cup in 1964.
Why is it that some individuals can perform a task—and do it well—while experiencing pain?
“There is a complex relationship between pain and attention, where pain can modulate attention and vice versa. Moreover, the interplay between these two factors differs from one person to the next,” explains Dr. Karen Davis.
Dr. Davis has shown that individuals can be classified as one of two types depending on how pain affects their performance in doing a task. In P-type individuals, pain impedes their ability to perform a task; whereas, in A-type individuals, like Bobby Baun, pain enhances their performance.
To gain a better understanding of the brain mechanisms that contribute to this divergent behaviour during pain, Dr. Davis and her PhD student Joshua Cheng led a study examining patterns of brain activity in these two groups.
First, 51 healthy participants were classified as either A-type or P-type based on their performance in a complex mental task in the presence and absence of a painful stimulus. Next, the participants underwent a functional MRI (fMRI) scan, while they were not thinking of anything in particular, to measure their spontaneous brain activity.
When I play hockey, my mind is so focused on the game and scoring a goal that I don’t feel my recurring back and knee pain,” confides Dr. Davis, an avid hockey player and Leafs fan.
-Dr. Karen Davis
The researchers focused their study on the activity of brain cells in two networks: the executive control (EC) network and the salience network. The EC network helps to optimize a person’s behaviour in response to what’s happening around them; whereas, the salience network is normally engaged when something like pain draws your attention.
Through their analysis, Dr. Davis and her research team discovered a link between spontaneous brain activity and task performance with pain. The synchrony of activity between the EC network and the salience network, as well as within the salience network, was more flexible in A-type individuals than P-type individuals. These findings suggest that brain communication is more flexible in A-type individuals—a feature that could be important for prioritizing task performance over pain, producing better performance.
Regarding her future work, Dr. Davis says, “We’d like to explore whether communication flexibility is disrupted in chronic pain and how it is altered by treatments for chronic pain—including surgery, medications and cognitive-behavioural therapy. This will improve our understanding of the mechanisms underpinning chronic pain, which will be instrumental for developing more effective and personalized therapies for this debilitating condition.”
Cheng JC et al. Neuroimage. 2017 Aug 15;157:61-68. Supported by the Canadian Institutes of Health Research and the Toronto General & Western Hospital Foundation.
Radiation therapy is simple in its concept: high-energy radiation can damage and destroy cells, so beams of radiation are directed at a tumour to kill cancer cells. However, the treatment must also carefully minimize the dose to nearby organs.
Actually creating a plan that balances these conflicting requirements can be incredibly complex—it requires dedicated time from a team of highly trained experts. Each patient’s anatomy and tumour shape are unique, and it takes a lot of clinical resources and expertise to create a high-quality plan.
That may not be the case for much longer. Dr. Thomas Purdie and his team, including Dr. Chris McIntosh, have used the power of artificial intelligence (A.I.) to develop a new system that can create a high-quality plan in minutes—faster than current approaches, which can take days.
The technology, known as AutoPlanning, uses machine learning to harvest information from a massive database of proven radiation therapy plans from Princess Margaret Cancer Centre. While no two patients are identical, there can be similarities. The AutoPlanning A.I. can evaluate many features in a patient’s images, and find other patients in the database with similar features. Then, it builds a radiation therapy plan for the new patient based on information in the plans of patients with similar features.
With thousands of high-quality plans to learn from, the system rapidly adapts and optimizes the plan to suit the new patient.
“The technology allows radiation medicine teams to take on more complex cases and provide precision medicine to more patients,” says Dr. Purdie.
Toronto’s stem cell and regenerative medicine ecosystem gained a major player with the establishment of a new biotechnology company, BlueRock Therapeutics, in December 2016. The company, co-founded by world-renowned UHN researchers, Drs. Gordon Keller and Michael Laflamme, will advance novel stem cell-based treatments for a variety of diseases, such as cardiovascular disease and Parkinson disease, in a state-of-the-art 10,000 square foot facility.
One of the first innovations that will be developed by the company is an approach to regenerate and repair damaged heart muscles, co-created by the two UHN researchers. Drs. Keller and Laflamme developed a way to coax stem cells into becoming specialized heart muscle cells called cardiomyocytes. These cells, when introduced into the heart, act like building blocks—incorporating into the heart tissue and making the heart stronger by repairing muscle damage caused by heart attacks or abnormal heart rhythms.
“We’ve had a lot of research breakthroughs in the past several years and with BlueRock we can now move them from the laboratory to the clinic to help patients,” said Dr. Laflamme during the launch event, which was attended by federal and provincial ministers and the Premier of Ontario.
BlueRock builds upon Toronto’s excellence in stem cell research."
BlueRock was made possible by Bayer AG and Versant Ventures, who provided US$225 million in seed funding. The funds, which represent one of the largest biotechnology investments in history, will be used to build and support research and development facilities in Toronto, New York and Boston. The Toronto facility will employ up to 70 scientists and technical staff when fully functional.
Sparked by the discovery of stem cells at UHN more than 50 years ago, the local stem cell research community is home to leading centres such as UHN’s McEwen Centre for Regenerative Medicine and the Centre for Commercialization of Regenerative Medicine. BlueRock now joins this vibrant cluster of excellence in regenerative medicine, reinforcing Toronto’s world-class reputation in the field.
“The concentration of stem cell research resources and expertise that we have is unparalleled,” says Dr. Keller, who is also the Director of the McEwen Centre. “Establishing BlueRock Therapeutics is a visionary move that will lead to new therapies for currently untreatable diseases.”
Difficulty swallowing, or dysphagia, affects over half of all stroke patients. Dysphagia in turn can cause patients to inhale food or drink into their lungs when trying to swallow, leading to pneumonia and increased risks of disability and death.
Identifying patients with dysphagia early allows the care team to bring in the services of a Speech Language Pathologist (SLP), who can recommend and implement strategies to reduce the risk of developing pneumonia.
How clinicians identify those patients is an area for improvement.
Screening tools, such as the Toronto Bedside Swallowing Screening Test (TOR-BSST©) developed by Krembil Affiliate Scientist Dr. Rosemary Martino’s team can identify patients at risk of dysphagia with a high degree of sensitivity. The TOR-BSST helps guide clinicians through a quick but systematic screening of the patient, including how they swallow water, to ensure any warning signs are caught and patients at risk are referred to a SLP.
However, more than half of acute stroke care institutions in Canada and the US do not use a formal screening tool. Instead, they detect swallowing problems by performing an informal assessment, in which a clinician makes a judgement as to whether a patient is at risk without evaluating all the possible symptoms.
In a recent study, Dr. Martino along with her students and colleagues used clinical data from before and after the implementation of the TOR-BSST at Toronto Western Hospital to compare the accuracy of dysphagia detection using the tool to that of the informal assessments. They found that the screening tool identified over 95% of patients at risk for dysphagia, whereas informal screens missed a high number of patients at risk: just 45% were identified and referred for specialized assessment and care.
“In an ideal health care system with unlimited resources, every patient would be seen by an SLP for a comprehensive swallowing assessment. However, in the real world properly validated screening tools are critical for directing the rarer and more expensive resources, such as an SLP, only toward those patients at risk for dysphagia,” Dr. Martino concludes.
This work was supported by the Canadian Stroke Network Summer Student Program, the Heart and Stroke Foundation, the University of Toronto and the Toronto General & Western Hospital Foundation. Dr. R. Martino holds a Tier 2 Canada Research Chair in Swallowing Disorders.
Sherman V, Flowers H, Kapral MK, Nicholson G, Silver F, Martino R. Screening for Dysphagia in Adult Patients with Stroke: Assessing the Accuracy of Informal Detection. Dysphagia. 2018 Mar 1. doi: 10.1007/s00455-018-9885-8
Looking at things from a different angle can often lead to new and better solutions. That’s because a fresh perspective can help to inspire creativity, innovative thinking and collaboration.
It’s also why Dr. Cristina Nostro and her team recently embarked on a new collaborative project to solve a particularly difficult research problem: how to reliably isolate a specific pancreatic cell type capable of improving current treatments for type I diabetes.
Type I diabetes is a chronic condition in which cells in the pancreas—known as beta cells—are destroyed so little to no insulin is produced. Without insulin, the body is unable to keep blood sugar levels within a healthy range. When blood sugar levels remain consistently high for a prolonged period of time, serious conditions can develop, including heart disease, vision loss, kidney disease and nerve damage.
Transplanting healthy beta cells into the pancreas can restore insulin production and decrease the number of insulin injections needed to maintain normal sugar levels. However, widespread use of this treatment is hampered by a limited supply of donor beta cells for transplantation.
Using stem cells, Dr. Nostro has addressed this issue by developing a reproducible method for generating large numbers of cells that can safely give rise to insulin-producing beta cells. The technique, which mimics what occurs during pancreas development, forces stem cells to mature into daughter stem cells (pancreatic progenitors) that then develop into insulin-producing beta cells.
Unfortunately, the technique also produces progenitors that mature into cells that do not produce insulin. The problem: these contaminating progenitors need to be removed before the therapeutic insulin-producing cells can be safely used in the clinic.
This new approach will help us to develop safer stem cell therapies for diabetes.”
-Dr. Cristina Nostro
Dr. Nostro teamed up with Dr. Thomas Kislinger to explore an entirely new approach to solving this problem. Together they identified specific proteins that are found on the surface of the pancreatic progenitors. They then used one of the proteins—known as Glycoprotein 2—to isolate the pancreatic progenitors and remove the contaminating cells. This allowed them to not only control the number but also the purity of the newly generated insulin-producing cells.
“Our long-term goal is to cure type I diabetes using transplants of insulin-producing cells, so it is crucial to have cells that are safe and pure,” explains Dr. Nostro. “The technique we’ve developed provides a better, more reliable method for generating large quantities of these cells for use in the clinic.”
Just like a large city, the body has a several systems in place to dispose of different types of waste. And when one of these systems malfunctions, serious problems can arise.
Dr. Tracy McGaha, a Senior Scientist at the Princess Margaret Cancer Centre, has shown that disrupting efferocytosis—the process through which dead cells are removed from the body—promotes the development of lupus. The findings of the study were published today in the prestigious journal Nature Immunology.
Lupus occurs when the immune system mistakenly attacks healthy tissues throughout the body, including those of the joints, skin, kidneys, blood, heart and lungs. The abnormal immune response can cause significant inflammation and damage to these parts of the body.
The cause of lupus and the immune mechanisms responsible for its damage remain elusive. This gap in knowledge has precluded the development of effective treatments that target the underlying cause of the disease.
“The link between lupus and efferocytosis is that they both involve the immune system,” explains Dr. McGaha. “In efferocytosis, specialized immune cells known as phagocytes seek out dead cells, then engulf and digest them—acting like the body’s trash collectors.”
The researchers showed that when phagocytes ‘eat’ dead cells, the immune system is suppressed through the action of a protein known as the aryl hydrocarbon receptor (AhR). In contrast, when phagocytes lacking AhR eat dead cells, the immune system is not suppressed and the body attacks healthy tissues, causing damage similar to what seen in lupus.
Dr. McGaha’s team also found that AhR activity can affect disease severity in an experimental model of lupus: disease symptoms worsen when AhR is inhibited, whereas disease symptoms improve when AhR is activated.
Dr. McGaha comments, “the results of our study suggest that AhR activity is a key mechanism that prevents the immune system from attacking normal tissues. We believe that this new knowledge could be exploited to not only develop new more effective treatments for lupus, but also to make the immune system better at destroying cells that have become cancerous.”
This work was supported by the National Institutes of Health, the Canada First Research Excellence Fund, the Swedish Medical Research Council, the Karolinska Institute (Sweden), the Canada Foundation for Innovation and The Princess Margaret Cancer Foundation. D De Carvalho holds a Tier 2 Canada Research Chair in Cancer Epigenetics and Epigenetic Therapy.
Shinde R, Hezaveh K, Halaby MJ, Kloetgen A, Charkravarthy A, da Silva Medina T, Deol R, Manion KP, Baglaenko Y, Eldh M, Lamorte S, Wallace D, Chodisetti SB, Ravishankar B, Lui H, Chaudary K, Munn DH, Tsirigos A, Madaio M, Grabrielsson S, Touma Z, Wither J, De Carvalho D, McGaha TL. Apoptotic cell–induced AhR activity is required for immunological tolerance and suppression of systemic lupus erythematosus in mice and humans. Nat Immunol. 2018 June. [abstract]
