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. Also, diagnosing the condition is 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
Dr. John Dick, Senior Scientist at Princess Margaret Cancer Centre is this year’s recipient of the Dr. Chew Wei Memorial Prize in Cancer Research administered by the University of British Columbia (UBC) Faculty of Medicine.
The award is presented annually to a Canadian physician or scientist who has made outstanding contributions toward the development of anti-cancer therapies. Valued at $50,000, the Dr. Chew Wei Memorial Prize in Cancer Research is among the most esteemed honours granted by a Canadian university.
Dr. Dick is internationally recognized for discovering the origins of leukemia through the identification of leukemia stem cells (LSCs)—the first type of cancer stem cells to be isolated and characterized. Since this landmark discovery, Dr. Dick has continued to advance the field by showing that LSCs are roadblocks to successful therapy and a root cause of relapse. This work has led to many clinical applications including new biomarkers to predict response to therapy as well as new therapeutic strategies for leukemia.
The honour adds to the remarkable list of awards that Dr. Dick has received over his career. His past distinctions include his election as a Fellow of the Royal Society of London, Fellow of the Royal Society of Canada and Fellow of the American Association for Cancer Research Academy. He has also received the William Dameshek Prize and the E. Donnall Thomas Prize from the American Society of Hematology, the KEIO Medical Science Prize from KEIO University in Japan and the Innovation Award from the International Society for Stem Cell Research.
The award will be presented to Dr. Dick at the UBC Faculty of Medicine’s National Research Awards Dinner this fall.
To read more about the prize, click here.
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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