Last month, UHN researchers were awarded nearly $1.4 million in funding from the Canada Foundation for Innovation for cutting edge research equipment. The investment, provided through the John R. Evans Leaders Fund, will support the following three projects from the Toronto General Hospital Research Institute, the Krembil Research Institute and the Princess Margaret Cancer Centre:
Cardiac Regeneration and Disease Modelling. Led by Dr. Sara Vasconcelos of Toronto General Hospital Research Institute, this project will develop realistic models of heart failure using advanced bioengineering methods. Dr. Vasconcelos will explore new regenerative medicine techniques to repair damaged hearts using stem cells and engineered blood vessels. The research will shed new light on the mechanisms of heart disease and how they are affected by related factors such as diabetes.
Defining Cancer and Immune Landscapes in Multiple Myeloma. A team comprising Drs. Trevor Pugh, Rodger Tiedemann and Suzanne Trudel of Princess Margaret Cancer Centre will use funding to advance research for multiple myeloma—a cancer that originates in the bone marrow and occurs in blood cells. The researchers will determine the genetic sequences of individual tumour cells to assess how these cells avoid detection by the immune system; find ways of boosting the immune response against cancer; examine the genetic features of multiple myeloma that enable the tumours to resist anti-cancer drugs; and reveal the primitive, cancer-initiating cells that are not destroyed by conventional treatments and that ultimately cause cancer re-growth.
Tracking down neurodegeneration in the human brain: from functional systems to the subcellular level. This project is being led by Dr. Gabor Kovacs at the Krembil Brain Institute and the Tanz Centre for Research in Neurodegenerative Disease. Funding will enable the research team to evaluate the distribution of neurodegeneration-related proteins in the functional systems of the human brain in three dimensions. The project will also reveal—at the molecular level—the interactions among these neurodegeneration-related proteins, as well as how they interact with other pharmaceutically targetable proteins (ie, proteins such as cell receptors, which are located at the surface of cells). The research will lay the foundation for the discovery of therapeutic targets for neurodegenerative diseases and diagnostic tests that could help to widen the treatment window for these diseases.
Congratulations to Drs. Vasconcelos, Pugh, Tiedemann, Trudel and Kovacs!
Total knee replacement surgery is a last-resort treatment for people whose osteoarthritis can no longer be managed through other approaches.
Although reduced physical function is a key decider for whether surgery is the right treatment, there is currently no clinically standardized way to measure physical function in individuals with knee osteoarthritis. A team of Krembil researchers compared and contrasted two ways that are often used to assess function: a physical test and a self-reported questionnaire.
The study, published in PloS ONE, revealed that self-reported physical function scores in younger individuals tended to be worse compared to performance-based scores. In older adults, self-reported and performance-based scores were more consistent.
“An osteoarthritis diagnosis can be perceived as untimely and upsetting for middle-aged adults (45-65 years of age), particularly as they tend to be more engaged in activities such as working and activities with young children. These perceptions and experiences of disruption to normal activities may be expressed by worse self-reported function relative to measured physical function,” explains Krembil Scientist Dr. Anthony Perruccio who led the study with then graduate student Jessica Wilfong.
Disagreement between self-reported and performance-based scores was also found in individuals with more intense knee pain. Additionally, discordance, depending on sex and obesity, was associated with:
The performance test used by the research team involved timing how long it took patients to stand up from a chair, walk a short distance and return to the chair to sit. Longer times indicated worse functionality. They compared the results of the performance test with how patients ranked their functionality on a questionnaire.
“Our research shows that self-reported and performance-based measures provide distinctive and complementary information that lend to a holistic understanding of a patient’s physical functionality and how it impacts their life,” says Dr. Perruccio.
This work was supported by the Toronto General & Western Hospital Foundation through the University Health Network Arthritis Program.
Wilfong JM, Badley EM, Power JD, Gandhi R, Rampersaud YR, Perruccio AV. Discordance between self-reported and performance-based function among knee osteoarthritis surgical patients: Variations by sex and obesity. PLoS ONE. 2020 Jul 30. doi: 10.1371/journal.pone.0236865.
The UHN Office of Research Trainees (ORT) is proud to announce the release of the latest issue of The ORT Times!
The ORT Times is UHN's monthly trainee-focused newsletter. It highlights news and editorials about trainee life, articles to help developing researchers get the most out of their training experience at UHN, tips on career development, and research training opportunities within and outside of UHN.
Feature Stories:
● The Viruses Within from Joe Walton
● Supervising an Undergraduate Student from Laura Aronoff
● Working with Multiple Supervisors from Scott Rich
● Submitting a Manuscript from Tyler Saumur
Featured Trainees: Angela Sekely from Princess Margaret Cancer Centre and Mi Lai from Toronto General Hospital Research Institute are featured this month!
Read and download the full issue now!
To see past issues of The ORT Times, please visit ORT’s website.
In response to a coronavirus infection, the body’s immune system mounts an inflammatory response against the virus. However, sometimes this inflammatory response is so sudden and strong that it becomes fatal.
Dr. Donald Weaver, a Senior Scientist and Director of Krembil Research Institute, recently showed in a pre-clinical study that furosemide, a small-molecule drug, has the potential to treat COVID-19 by reducing the harmful inflammation caused by the infection.
Furosemide is a diuretic commonly prescribed to treat high blood pressure, fluid build-up in the lungs and chronic kidney disease. It can be administered orally, intravenously, and by inhalation. It is also safe, readily available and part of WHO’s Essential Medicines List.
It takes many years to bring a new drug to market. To accelerate the development of treatments for COVID-19, Dr. Weaver’s team had turned to the strategy of repurposing existing drugs.
Searching through a library of 1,136 small molecules produced by the body, the research team found one molecule with significant anti-inflammatory potential known as 3-hydroxyanthranilic acid (3-HAA). They then looked for approved drugs that are similar in structure to 3-HAA.
Of the few candidates that were shortlisted, furosemide was the most promising. Cell culture studies revealed that furosemide inhibited the production of pro-inflammatory molecules and promoted the production anti-inflammatory molecules.
“Our pre-clinical study suggests that furosemide may be a candidate for repurposing as an inhaled therapy against COVID-19,” says Dr. Weaver.
“Furosemide has been shown to reduce bronchial inflammation associated with asthma in previous clinical studies. We are currently pursuing a clinical study to assess whether it can reduce the severity of COVID-19 infection.”
This work was supported by the Canada Research Chair Program and the Toronto General & Western Hospital Foundation. D Weaver holds a Tier 1 Canada Research Chair in Drug Design for Protein Misfolding Disorders.
Wang Z, Wang Y, Vilekar P, et al. Small molecule therapeutics for COVID-19: repurposing of inhaled furosemide. PeerJ. 2020 Jul 7. doi:10.7717/peerj.9533.
This year, the Royal Society of Canada has selected the following four UHN Researchers as 2020 Fellows: Drs. Cheryl Arrowsmith, Karen Davis, Rama Khokha and Ming-Sound Tsao.
This distinction is bestowed to Canadian scholars, artists and scientists who have made outstanding contributions in their field. All four scientists have extraordinary track records marked by original and ground-breaking discoveries.
Dr. Cheryl Arrowsmith, Senior Scientist at Princess Margaret Cancer Centre, is internationally recognized for her pioneering contributions to the multidisciplinary field of structure-guided drug discovery. As cofounder of a unique international public-private-partnership, the Structural Genomics Consortium, she leads its transformative Open Science program that is catalyzing the discovery of new medicines. Her research has developed, exploited and distributed thousands of unencumbered ‘chemical probes’ that are revolutionizing the creation of precision medicines for multiple diseases, especially cancer. Her work has led to authorship of over 340 scientific articles that have been cited over 30,000 times.
Dr. Karen Davis, Senior Scientist at Krembil Research Institute (Krembil), is a renowned neuroscientist whose research program is focused on exploring the brain mechanisms underlying chronic pain and traumatic injuries, pain-attention interactions, factors associated with treatment and recovery, and neuroethical issues related to the brain imaging of pain. She is currently the Research Division Head at Krembil and is a Professor in the Department of Surgery and the Institute of Medical Science at the University of Toronto. Dr. Davis has also been inducted into the Johns Hopkins Society of Scholars, the Canadian Academy of Health Sciences and is currently the President of the Canadian Pain Society (2020-2022). To date, she has published her work in over 190 papers that have garnered more than 20,000 citations.
Dr. Rama Khokha, Senior Scientist at Princess Margaret Cancer Centre, is internationally recognized for her work in tumour biology, particularly in the context of the tumour microenvironment and stem cell niches. Her research has advanced the development of molecularly targeted strategies to treat and prevent aggressive breast and bone cancers. Her work has laid the foundation for ongoing international clinical trials. Her many distinctions include the Canadian Cancer Society's prestigious Robert L. Noble prize and a Tier 1 Canada Research Chair in Adult Tissue Stem Cell Niches. Her influential work has culminated in over 150 peer-reviewed publications that have been cited over 19,000 times.
Dr. Ming-Sound Tsao, Senior Scientist and Pathologist at Princess Margaret Cancer Centre, is a leader in the field of translational lung cancer research. His research has led to the development of biomarkers for EGFR therapy in lung cancer and uncovered prognostic gene signatures that can predict which early stage lung cancer patients will benefit from adjuvant chemotherapy. He led the first translational biomarker study of the Canadian Cancer Trials Group, which showed that tumours with EGFR gene aberrations, including mutations responded better to an EGFR inhibitor. This contributed to current molecular testing practices for precision medicine in advanced non-small cell lung cancer. Dr. Tsao has received the Canadian Cancer Society’s Harold Warwick Award and has been included in the global list of Highly Cited Researchers (2018, 2019) by Clarivate Analytics. His work is published in roughly 600 peer-reviewed articles that have garnered more than 71,000 citations.
Congratulations to Drs. Arrowsmith, Davis, Khokha and Tsao!
A study led by Dr. Carolina Alba at the Toronto General Hospital found that ER admissions and hospitalizations for heart failure dropped by around 40% during the pandemic.
The COVID-19 pandemic has resulted in drastic changes to the health care system. “Our findings provide an early glimpse into the impacts of the pandemic on the care of those with heart failure,” says Dr. Alba, who is a Scientist at Toronto General Hospital Research Institute.
For the study, the research team looked at the number of patients presenting to hospital for worsening heart failure symptoms between March 1 and April 19. These dates capture the public lockdown in Ontario, which began on March 12. By comparing data before and after the pandemic, the team found an average decrease of 43.5% in emergency department visits and a decrease of 39% in hospitalizations for heart failure.
Despite the decrease, the study also revealed that rates of hospitalization or intensive care unit stays did not increase among patients presenting to the emergency department for heart failure during the pandemic.
According to the authors of the study, these observations are likely the result of complex public health and social factors. For example, patients may be more cautious about going to hospitals for fear of contracting COVID-19. The effects could also be the result of ‘silver linings’ from the pandemic and physical distancing. For example, stay-at-home directives may have enabled patients to better manage their conditions, eat healthier and receive care virtually, leading to less hospital visits.
“While we are not sure of the underlying causes and effects, reduced hospital visits pose a serious threat. Over time, these reductions may lead to deteriorating health in those with chronic conditions and other individuals with complex health issues,” says Dr. Alba. This threat is supported by additional findings in the study, which suggest that early trends for in-hospital deaths are rising.
The results of this study add to the growing body of evidence from around the world—in particular from the United States—that show reduced hospitalization rates for these and other conditions, such as stroke.
“While it is still too early to predict whether the COVID-19 pandemic has caused collateral damage to the care received for chronic conditions, our findings are a call to action,” says Dr. Alba. “As the situation evolves, there is a strong need to closely monitor chronic disease management and care during the pandemic. As well, more education is necessary so that the public knows that emergency care is still available for those who need help.”
This work was supported by Toronto General & Western Hospital Foundation.
Frankfurter C, Buchan TA, Kobulnik J, Lee DS, Luk A, McDonald M, Ross HJ, Alba AC. Reduced Rate of Hospital Presentations for Heart Failure During the COVID-19 Pandemic in Toronto, Canada. Can J Cardiol. 2020 Jul 17:S0828-282X(20)30599-7. doi: 10.1016/j.cjca.2020.07.006.
This month, former UHN trainee Dr. Luka Milosevic joins the Krembil Research Institute as their newest Scientist. Dr. Milosevic is a biomedical engineer, researcher and intraoperative neurophysiologist.
Dr. Milosevic’s research has provided his field with a deeper understanding of how electrical impulses that are generated during deep brain stimulation (DBS) regulate brain activity. Most notably, he found that DBS can induce long-lasting changes to brain activity that persist after stimulation—a key finding in the search for new treatments for neurological disorders, such as Alzheimer disease and Parkinson disease.
Dr. Milosevic also plays a clinical role monitoring patients’ brain activity during surgeries to guide the placement of DBS devices.
“It is very fulfilling knowing that with our research and with each surgery we are helping to improve the quality of life and independence of the individuals we treat.”
Start-up funding will help Dr. Milosevic build a research program with a diverse team of talented trainees. His team will leverage the access to intracranial human brain recordings in order to gain a deeper understanding of physiological processes underlying disorders of the nervous system, with the overall aim of developing novel therapeutic brain stimulation approaches.
Dr. Milosevic is cross-appointed to the Institute of Biomedical Engineering at the University of Toronto as an Assistant Professor and will collaborate with CRANIA and The KITE Research Institute as an Affiliate Scientist.
“Krembil is the world-leading center for deep brain stimulation research and is home to unique and state-of-the-art research facilities, such as the CRANIA neuromodulation suite. I’m looking forward to collaborating with the incredibly talented scientists at Krembil and contributing positively to the lives of individuals living with neurological conditions.”
Most recently, Dr. Milosevic was a Postdoctoral Fellow at the Institute for Neuromodulation and Neurotechnology at the University of Tübingen in Germany. He received a PhD in Biomedical Engineering from the University of Toronto, where he was supervised by Dr. Milos Popovic, Director of The KITE Research Institute, and Dr. William Hutchison, Senior Scientist at the Krembil Research Institute.
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