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Four research projects at UHN have been funded by the Fast Grants initiative. They were selected based on their potential to achieve real benefits and to help address the COVID-19 pandemic within six months.
The Fast Grants initiative lives up to its name: projects are reviewed and funding is released to successful applicants within 48 hours of submission. As of April 25, 2020, the program awarded 102 grants and provided $18M to researchers worldwide.
The following four UHN-led projects were successfully funded:
● Dr. Brian Raught, Senior Scientist, Princess Margaret Cancer Centre, UHN
Two cutting-edge screening technologies will be used to identify: 1) new drug targets for the treatment of COVID-19, and 2) drugs approved by the U.S. Food and Drug Administration that have activity against the SARS-CoV-2 virus.
● Dr. Ewan Goligher, Scientist, Toronto General Hospital Research Institute (TGHRI), UHN
● Dr. Patrick Lawler, Scientist, TGHRI, UHN
A trial to determine whether high-dose blood thinners can improve survival in patients with COVID-19. COVID-19 is associated with a significantly increased tendency for blood clotting and this may lead to life-threatening respiratory failure and heart failure. Hospitalized patients are routinely treated with a low dose blood thinner to prevent formation of blood clots; this international clinical trial will establish whether treatment with high dose blood thinners can prevent the need for intubation and reduce the risk of death in hospitalized patients with COVID-19.
● Dr. Steven Friedman, Clinician Investigator, TGHRI, UHN;
● Dr. Susan Poutanen, Microbiologist, UHN and Mount Sinai Hospital
A study to evaluate a new saliva-based test for the COVID-19 virus (ie, SARS-CoV-2). This new approach would serve as an alternative to existing ‘nasopharyngeal swab’ testing methods and help overcome the current shortages in swabs and related testing reagents. It would also reduce risks to health care workers because the new test would not require them to be in close proximity to the individuals being tested. In addition to reducing the risk of infection, the new test would reduce the need for personal protective equipment, which is also in short supply.
● Dr. Kevin Kain, Senior Scientist, TGHRI, UHN
● Dr. Megan Landes, Clinician Investigator, TGHRI, UHN
A study to assess the safety and effectiveness of the drug known as hydroxy-chloroquine at preventing COVID-19. The study will be carried out over a three-month period and enable the researchers to test whether the drug prevents COVID-19 in health care workers that are at high risk for exposure to the virus.
UHN is thankful to all the sponsors that have contributed to the Fast Grants initiative through contributions made to the Thistledown Foundation. A special thank you to Shopify Inc. CEO Tobi Lutke and his spouse Fiona McKean, who engaged with research institutions and set this initiative in motion. For a full list of current donors and updates to funded projects, see: https://fastgrants.org/
Congratulations to all researchers involved in this important work!
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:
• Managing Research Disruptions
• Optimizing Working from Home
• Taking Care During Isolation
• Make Science Clear
Conference Reports: Read conference reports from Dr. Sara Rapic and Stephanie Poon.
Read and download the full issue now!
To see past issues of The ORT Times, please visit ORT’s website.
To help the research community stay on top of the latest COVID-19 research, Dr. Bo Wang, lead AI scientist at the Peter Munk Cardiac Centre and Scientist at the Techna Institute, released a new tool for exploring scientific literature.
The tool, called CiteNet, is a search engine that uses natural language processing—a type of artificial intelligence algorithm—to find relevant scholarly publications.
“CiteNet is different from traditional search engines because it uses key papers to search for related scientific literature, rather than keywords,” says Duncan Forster, one of the developers of the tool.
“Instead of finding a ‘needle in a haystack’, which is the approach of traditional search engines, CiteNet is designed primarily for researchers who want to explore the literature around a topic without a specific question in mind,” explains Dr. Wang.
For example, if you want to learn about the scientific dialogue around COVID-19 transmission and know of an article on the topic, starting the search with that article will lead you to the latest relevant works on the topic.
Here are the key points to keep in mind when using CiteNet to explore the latest research:
The team is working on linking the pre-print articles to published articles and improving the accuracy and relevance of the searches.
“Currently we are focusing on bioRxiv and medRxiv to help researchers keep up to date with the latest COVID-19 research,” says Dr. Wang. “In the future, we would like to index everything that's available and explore more ways for CiteNet to help solve research problems.”
A video tutorial for CiteNet is available here.
UHN has launched a research study to determine the prevalence of coronavirus infection in health care workers.
The study, titled Research Platform to Screen and Protect Healthcare Workers—or RESPECT for short, will determine how common asymptomatic COVID-19 infection is among health care workers at UHN.
“We urgently need to understand the disease and to quickly develop and implement screening strategies to protect our patients and health care workers,” says Dr. Deepali Kumar, Clinician Investigator at Toronto General Hospital leading the study.
Asymptomatic and pre-symptomatic individuals can transmit COVID-19, which can be a significant risk in health care settings, especially in long-term care facilities.
“As Canada’s largest research hospital, UHN is uniquely positioned to rapidly initiate, conduct and coordinate multisite research,” says Dr. Kumar. “We will use our expertise in supporting multisite clinical trials to standardize the collection of biospecimens from health care workers and deliver them to research laboratories for testing.”
Through this study, the research community will contribute to the fight against COVID-19 in the following three ways:
● by developing alternative COVID-19 tests that do not use precious clinical laboratory resources needed for existing testing
● by establishing a centralized system to measure the prevalence of COVID-19 and to deliver test results back to individuals
● by finding ways to share data and test results in real time
Participation in the study is voluntary. Other research hospitals are interested in joining RESPECT and the team is working to expand the platform across the province and the country.
“Our staff have been working around the clock to ensure that we have the infrastructure to fast track this study in order to support our frontline staff,” says Brad Wouters, EVP Science and Research at UHN. “It’s remarkable what we can accomplish as a team during these challenging times.”
This study is supported by the MSH-UHN Academic Medical Organization COVID-19 Innovation Fund, The Princess Margaret Cancer Foundation and the Toronto General & Western Hospital Foundation.
Research on COVID-19 is skyrocketing. Areas of interest span from risk of infection, to prevention, treatment, and coping with the stress and anxiety of the moment.
To help accelerate your research, the UHN Science of COVID-19 Portal provides resources you can trust to:
● Keep up to date with the latest research findings
● Connect with researchers
● Watch recorded grand rounds of experts presenting their work
● Ask questions via the ‘Emerging Evidence’ page, which will be answered by information specialists using the latest evidence
Access these resources, and more, on the Science of COVID-19 Portal: http://uhnlibraries.ca/covid19
Resources are constantly being added to the Portal. For more information, please email Tim Tripp, Director, UHN Library & Information Services.
One of the most effective ways to stop the spread of COVID-19 is through practicing good hand hygiene.
Because of this, it is particularly important to understand what affects whether good hand hygiene is practiced—particularly in a health care setting.
“Currently, hand hygiene compliance is audited. This means that an auditor shows up unannounced, observes hand hygiene for a short period of time, then leaves with the results,” says Dr. Alon Vaisman, a UHN Clinician in Quality and Innovation. “We wanted to see whether the act of auditing affected how often staff washed their hands.”
It is well known that people behave differently when they know they are being watched—a phenomenon known as the Hawthorne effect.
To test the Hawthorne effect on hand hygiene in a health care setting, Dr. Vaisman ran the study at two transplantation hospital wards. Auditors visited at random times and recorded hand hygiene practices for an hour at a time. These findings were compared to hand hygiene practice in the absence of auditors, which was measured using remote sensors.
“When health care workers were not being observed, hand hygiene was practiced at 40% of all potential opportunities. When auditors were present, this doubled to around 80%,” says Dr. Vaisman. “Notably, the Hawthorne effect was limited to only the short and rare occasions that auditors were present. It also changed based on time of day and location of the auditor.”
“It’s important to note that this study was run under normal work conditions with no threat of a pandemic. While our findings cannot be generalized to the current extraordinary circumstances, they do suggest that in a post-COVID-19 world, we will need to do more than just auditing—new, more effective ways to promote best practices are needed,” says Dr. Susy Hota, UHN’s Medical Director, Infection Prevention and Control, and one of the study authors.
To address this issue, UHN is already exploring innovative approaches to improve hand hygiene, including the use of a wearable badge that vibrates and beeps to remind health care workers to wash their hands.
“We cannot rely on being observed as a reminder for hand hygiene to be performed. We must find more effective ways to promote hand hygiene to protect ourselves, colleagues and patients,” says Dr. Vaisman.
This work was supported by the Toronto General & Western Hospital Foundation.
Vaisman A, Bannerman G, Matelski J, Tinckam K, Hota SS. Out of sight, out of mind: a prospective observational study to estimate the duration of the Hawthorne effect on hand hygiene events. BMJ Qual Saf. 2020. doi:10.1136/bmjqs-2019-010310.
A team of researchers at UHN’s Princess Margaret Cancer Centre (PM) has developed a comprehensive way to map the ability of molecules on the surface of cancer cells to serve as immunotherapy targets.
“Immunotherapy is quickly becoming a gamechanger, and is now considered—along with surgery, radiotherapy and chemotherapy—a cornerstone in the fight against cancer,” says Dr. Naoto Hirano, Senior Scientist at PM. “However, a major drawback of current immunotherapies is that they often only work in a fraction of patients. It is also very difficult to predict which patients will benefit.”
To overcome this limitation, the research team—including postdoctoral fellows Kenji Murata and Munehide Nakatsugawa—developed a technique that greatly expands how immunotherapy targets cancer so that more people might benefit from the treatment.
In cancer immunotherapy, certain immune cells—known as killer T cells—are temporarily isolated from patients. They are then ‘taught’ to target certain features, known as antigens, on the surface of cancer cells. In order for T cells to recognize these antigens, the antigens must be chopped into fragments called peptides and loaded onto a larger molecule known as type I human leukocyte antigen (HLA) complex, of which there are many different types.
The T cells are then injected back into patients and, if the immunotherapy is successful, begin to seek out and destroy the cancer cells.
Currently, immunotherapy targeting is limited. Only a few types of HLAs are used, which are found in only a subset of people and ethnic groups. Furthermore, only a select number of peptides, which are present in a fraction of the cancer cells, are used.
To address this, and to increase the diversity of targeting approaches, the researchers used immune cell samples from eight different individuals with melanoma. Using these samples, and a new streamlined approach, they were able to test the ability of 25 different types of HLAs and 800 different peptides to target the cancer.
The researchers also identified potent new peptides derived from well-established cancer antigens—called MART1 and NY-ESO1—that are present on a wider number of cancer cells than currently used antigens.
“By expanding the diversity of targeting approaches, our strategy allows for a more complete examination of the immune response. It opens the door for the development of immunotherapies that are effective in a broader group of patients,” concludes Dr. Hirano.
To read more, see the press release. The research study was supported by the Ontario Institute for Cancer Research, The Princess Margaret Cancer Foundation, Mitacs, the Province of Ontario, and the Natural Sciences and Engineering Research Council of Canada.
Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma. Murata, K, ..., Naoto, H. eLife 2020;9:e53244 doi: 10.7554/eLife.53244.
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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