At UHN, research is in our nature.
As Canada’s largest research hospital we are driven by curiosity to explore the nature of health. These explorations advance our shared vision of A Healthier World.
The latest UHN Research Report, which is titled “Health is in Our Nature”, showcases this. It demonstrates how our community of scientists, trainees and staff have a deep-rooted commitment to improve the health and wellbeing of people around the world through research, discovery and innovation.
The report features the following stories from UHN’s research institutes:
● Scientists at The KITE Research Institute are examining how cardiac rehabilitation programs are helping seniors recover from coronary artery disease
● Krembil Research Institute scientists are discovering new types of cells that may help stimulate breathing—with important implications for those who have lost this ability as a result of spinal cord injury
● McEwen Stem Cell Institute researchers are taking a united approach to develop novel cell-based therapies for diseases of the heart, brain, liver, pancreas and blood
● Princess Margaret Cancer Centre researchers are developing simple, yet revolutionary blood tests to detect and classify cancer
● Techna Institute researchers are finding new and improved ways of visualizing cancers, helping physicians to more accurately diagnose the disease and design better treatment plans
● Toronto General Hospital Research Institute scientists are studying the various cell types that make up the liver to create the most detailed map of the organ to date
The report also highlights the accomplishments of our three foundations—The Princess Margaret Cancer Foundation, the Toronto General & Western Hospital Foundation and the Toronto Rehab Foundation. Without their commitment to research, UHN would not be able to engage in cutting edge and transformative discoveries needed to deliver better care for patients.
Click here to read this year’s report.
A study of Ontario early-stage cervical cancer patients has shown that there is a higher rate of death and cancer recurrence in patients who are treated with a radical hysterectomy using minimally invasive surgery (MIS) compared to those who undergo traditional surgery.
Women with early-stage cervical cancers are usually treated with a radical hysterectomy where the uterus, cervix and surrounding tissues are surgically removed. The MIS approach has been widely used to perform these surgeries; however recent studies have started questioning its safety.
This study, led by Princess Margaret Cancer Centre scientist Dr. Sarah Ferguson, examined the outcomes of 958 patients in Ontario who had radical hysterectomy by either MIS or traditional surgery, from 2006 to 2017.
Dr. Ferguson and her team found that, within five years after surgery, deaths occurred in 12.5 percent of those receiving MIS in contrast to 5.4 percent of those undergoing traditional surgery. Moreover, cancer recurred in 16.2 percent of patients receiving MIS, compared to 8.4 percent of those undergoing traditional surgery. As a result of these findings, the MIS procedure is no longer used at UHN in patients with early-stage cervical cancers.
"Surgeons believed that minimally invasive radical hysterectomy was safe because it was shown to be safe for many other cancers, such as endometrial cancer," said Dr. Maria Cusimano, the lead author of the study. "Our study shows the opposite."
Both Drs. Cusimano and Ferguson emphasize that these results refer to only a small proportion of patients with a specific stage of cervical cancer. They do not apply to the use of MIS hysterectomy for endometrial cancer or other non-cancerous gynecologic conditions.
Drs. Cusimano and Ferguson are now working to understand why MIS has a different effect on this particular subset patients, and whether altering the MIS technique can make a difference in outcomes.
This work was supported the Rose Torno Chair Award, the Department of Obstetrics & Gynecology at Mount Sinai Hospital/University Health Network, The Princess Margaret Cancer Foundation and by ICES, which is funded by the Ontario Ministry of Health & Long-Term Care.
Cusimano MC, Baxter NN, Gien LT, Moineddin R, Liu N, Dossa F, Willows K, Ferguson SE. Impact of surgical approach on oncologic outcomes in women undergoing radical hysterectomy for cervical cancer. Am J Obstet Gynecol. 2019 Jul 6. pii: S0002-9378(19)30893-2. doi: 10.1016/j.ajog.2019.07.009.
The Canada Foundation for Innovation (CFI) announced over $1.46 million in funding for advanced research infrastructure at University Health Network. These investments, provided through CFI’s John R. Evans Leaders Fund, will support the following four projects at the Toronto General Hospital Research Institute (TGHRI), Princess Margaret Cancer Centre (PM) and the McEwen Stem Cell Institute (McEwen):
• Harnessing Regulatory Immune Cells to Promote Transplantation Tolerance. Led by TGHRI Scientist Dr. Sarah Crome, this project will investigate the function of a newly discovered population of cells that regulate the body’s immune response and its role in organ transplantation. This research will refine our understanding of the root causes of transplant rejection and enable novel cell-based immunotherapies to be developed.
• Developing New Interventions for Breast and Lung Cancer. Led by PM Senior Scientist Dr. Rama Khokha and Clinician Scientist Dr. Benjamin Lok, this project will enable identification of molecular targets of breast cancer in women who are at higher risk of the disease in order to develop preventive treatment strategies (Dr. Khokha). The project will shed light on how cancer develops resistance to treatment by studying the underlying mechanisms of treatment resistance in the circulating tumour cells of lung cancer patients (Dr. Lok).
• DNA Damage and Cellular Physiology: Rewiring for a Cure. Led by PM Scientist Dr. Shane Harding, this project will enhance our understanding of how cells sense DNA damage, how they repair this damage and the consequences of these repairs. The overall goal is to design new interventions that selectively prevent cancer cells from repairing themselves without harming healthy cells.
• Generation of Stem Cell-Derived Pacemaker Cells for Biological Pacemaker Applications. Led by McEwen Scientist Dr. Stephanie Protze, this project aims to identify approaches for growing biological pacemaker cells—cells that could be used to develop a ‘biological pacemaker’ as a safer alternative to electronic pacemakers.
These funds are part of over $32M awarded to 40 universities that will support 261 infrastructure projects across Canada. The announcement was made on August 12 by the Honourable Kirsty Duncan, Minister of Science and Sport.
By providing key support for advanced research infrastructure, the John R. Evans Leaders Fund helps to attract and retain top talent, and enables the acquisition of equipment for new and/or existing research laboratories.
Congratulations Drs. Crome, Khokha, Lok, Harding and Protze!
A cross-disciplinary team of pathologists, physicians and scientists at University Health Network have defined a new way to classify the most common type of pancreatic cancer. The new classification system better reflects clinical outcomes than current methods.
The focus of the study was a cancer known as pancreatic ductal adenocarcinoma (PDAC), which is one of the most lethal of all cancers, with a five-year survival rate of less than 10 per cent.
“Although histological evaluation—looking at the tissue under the microscope—has served as the standard method of diagnosing and classifying PDAC, molecular analysis have since revealed two molecular subtypes that can stratify patients based on clinical outcomes.” says Dr. Sangeetha Kalimuthu, the lead author of the study, and gastrointestinal pathologist at the University Health Network.
She teamed up with Dr. Runjan Chetty, from UHN’s Laboratory Medicine Program, and Dr. Steven Gallinger, from UHN’s Hepatobiliary/Pancreatic Surgical Oncology Program, to explore whether this new molecular information could be used to revise and improve how pathologists classify these cancers.
The group assessed over 800 histological tumour tissue slides from 86 patients with PDAC. The slides were linked to their respective molecular profiles and patient outcome data. Combined, the data enabled the team to develop a revised two-tiered pattern-based classification system that provides more information about the cancer versus the current three-tiered system.
“The current three-tiered system—which grades tumours as well, moderate or poor—is limited in that the majority of tumours fall within the moderate category. This provides little insight when deciding on treatment plans. Our two-tier system overcomes this issue, while serving as a better predictor of outcomes,” says Dr. Chetty, senior author of the study.
This new classification system provides pathologists with a quick and affordable way to better classify PDACs and to identify the most aggressive tumours. Of the findings, Dr. Steve Gallinger a co-author in the research, says, “This study is an elegant demonstration of the potential of personalized medicine, with the promise of improved outcomes for our patients."
N Kalimuthu S, Wilson GW, Grant RC, Seto M, O'Kane G, Vajpeyi R, Notta F, Gallinger S, Chetty R. Morphological classification of pancreatic ductal adenocarcinoma that predicts molecular subtypes and correlates with clinical outcome. Gut. 2019 Jun 14. pii: gutjnl-2019-318217. doi: 10.1136/gutjnl-2019-318217.
Concussions are a common type of injury in contact and collision sports, such as football and hockey. They are caused by a blow or jolt to the head or body that damages the brain.
Athletes with a history of repeated concussions are at an increased risk of developing a neurodegenerative condition known as chronic traumatic encephalopathy (CTE). The condition impairs mental function and memory and can cause behavioural changes, such as aggression or depression.
“We do not fully understand how CTE develops or why it develops in some people with multiple concussions but not others. Diagnosing the condition is also a challenge because many of its symptoms overlap with those of other neurodegenerative diseases, such as Alzheimer disease,” says Dr. Carmela Tartaglia, a Clinician Investigator at Krembil Research Institute.
To begin addressing these gaps in knowledge, a team of researchers led by Dr. Tartaglia recently published a study examining 22 former professional athletes—including hockey and football players, as well as a snowboarder—who sustained multiple concussions throughout their careers.
The researchers measured the levels of total tau and beta-amyloid proteins in the cerebrospinal fluid of each athlete. These proteins are frequently used in the diagnosis of Alzheimer disease. The researchers also assessed the athletes’ brain structure using magnetic resonance imaging and brain function through neuropsychological tests.
They discovered that the former athletes could be divided in two groups based on their total tau levels: one group had significantly higher tau in their cerebrospinal fluid than healthy participants without a history repeated concussions, whereas the other group had levels comparable to those in healthy participants. The researchers also found that athletes in the high tau group displayed some impairments in their mental function and showed changes in their brain structure, both of which are indicative of neurodegeneration.
“Our findings suggest that high total tau levels could be a sign of neurodegeneration in individuals who have sustained multiple concussions,” says Dr. Tartaglia. “Detecting evidence of neurodegeneration is the first step towards being able to provide a treatment. Not everyone with multiple concussions gets CTE or other neurodegenerative diseases, so being able to detect those with evidence of disease is important for targeting treatment to the right person.”
This work was supported by the PSI Foundation, the Canadian Institutes of Health Research, and the Toronto General & Western Hospital Foundation. Dr. Tartaglia holds the Marion and Gerald Soloway Chair in Brain Injury and Concussion Research.
Taghdiri F, Multani N, Tarazi A, Naeimi SA, Khodadadi M, Esopenko C, Green R, Colella B, Wennberg R, Mikulis D, Davis KD, Goswami R, Tator C, Levine B, Tartaglia MC. Elevated cerebrospinal fluid total tau in former professional athletes with multiple concussions. Neurology. 2019 Jun 4. doi: 10.1212/WNL.0000000000007608.
Up to 84% of Canadians will experience low back pain at some point in their life.
Back pain can be caused by many things, and patients sometimes have to wait a long time before they can see a specialist to have the cause of their back pain diagnosed—years in some cases. This is much too long for some back pain-causing conditions such as axial spondyloarthritis (SpA).
SpA is a form of arthritis that affects the spine and can produce back pain and stiffness. If left untreated, it can lead to severe pain, back deformities and significant disability.
One of the factors that delays diagnosis is the lack of access to rheumatologists, who are doctors specialized in the care of arthritis and other diseases that affect the musculoskeletal system.
A new study led by Krembil Clinician Investigator Laura Passalent examined whether an alternative model of care could help accelerate the detection of SpA for those living with back pain.
The alternative model involved using physiotherapists to supplement the role of rheumatologists. The physiotherapists were provided with additional training to determine whether back pain is likely to be caused by SpA. While physiotherapists typically diagnose and treat different types of injuries, diagnosing SpA is traditionally outside of the scope of their role.
As part of the study, the specially trained physiotherapists assessed 57 patients with back pain for SpA. The records of the same patients were also independently assessed by three rheumatologists.
Ms. Passalent and the other researchers involved in the study found that the diagnoses offered by the physiotherapists agreed with those provided by the rheumatologists up to 80% of the time. The assessment offered by each of the three rheumatologists also matched up to 80% of the time. These findings indicate that the specially trained physiotherapists are comparable to rheumatologists at diagnosing SpA.
“Our study suggests that health care practitioners extending their role, with suitable training, could help reduce bottlenecks in the health care system and improve access to care for SpA patients,” says Ms. Passalent.
This work was supported by the Canadian Initiative for Outcomes in Rheumatology cAre (CIORA).
Passalent L, Hawke C, Lawson D, Omar A, Alnaqbi K, Wallis D, Steinhart H, Silverberg M, Wolman S, Derzko-Dzulynsky L, Haroon N, Inman RD. Advancing early identification of axial spondyloarthritis: An interobserver comparison of extended role practitioners and rheumatologists. J Rheumatol. 2019 May 1. doi: 10.3899/jrheum.180787
Research conducted at UHN's research institutes spans the full spectrum of diseases and disciplines, including cancer, cardiovascular sciences, transplantation, neural and sensory sciences, musculoskeletal health, rehabilitation sciences, and community and population health.
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