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Welcome to the latest issue of Research Spotlight. As Canada’s largest research hospital, UHN is a national and international source for discovery, education and patient care. This newsletter highlights top research advancements across UHN and from over 1000 researchers appointed at our institutes. Stories in this month’s issue:... Listen to Your Heart: During the COVID-19 pandemic, fewer people are visiting the hospital for heart disease. Exposing the Enemy Within: Study reveals that ancient DNA regions are key to activating the immune system against cancer. From Stem Cells to Liver Cells: Researchers use stem cells to generate liver cells that release vital blood clotting protein. Same Virus, Different Countries: Study reveals how health policies and actions have impacted COVID-19 caseload and mortality. Read these stories and more online here: http://www.uhnresearch.ca/news/research-spotlight-16 To read previous issues, see the newsletter archive: http://www.uhnresearch.ca/newsletters

Genomics Researcher Honoured: Dr. Trevor Pugh has been named one of Canada’s Top 40 Under 40 for 2020. Princess Margaret Senior Scientist Dr. Trevor Pugh has been named a recipient of Canada’s Top 40 Under 40 for 2020. The annual award was founded by Caldwell and recognizes 40 exceptional Canadian leaders who are visionaries, creative problem-solvers, inspire others, give back to the community and are under the age of 40. ... Dr. Pugh and his fellow awardees were selected from over 900 nominees by an independent advisory board, comprising more than 25 business leaders from across Canada. Honourees were chosen on four key criteria: vision & innovation, leadership, impact & influence, and social responsibility. When told that he had won, Dr. Pugh was elated. I could not believe it, he said. I’m tremendously excited. I really look forward to connecting with the Top 40 Under 40 community. It is very gratifying to see genome science and translational sciencewhich has a direct impact on patient carebe recognized as an important field along with business luminaries. Dr. Pugh is a world-leading cancer genomics researcher and molecular geneticist who focuses on using comprehensive genome profiling and technologies to guide the treatment of patients. After receiving a PhD in medical genetics from the University of British Columbia, he completed his postdoctoral work at Harvard Medical School, the Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, as well as the Dana-Farber Cancer Institute. He leads a multidisciplinary lab with 24 staff and trainees, and oversees 55 research staff across some of the largest genome facilities in Canada at the Ontario Institute for Cancer Research (OICR) and Princess Margaret Cancer Centre. He is the Director of Genomics at OICR and also an Associate Professor in the Department of Medical Biophysics at the University of Toronto. Dr. Pugh is also listed on the 2019 Highly Cited Researchers List by Clarivate Analytics. This list recognizes researchers whose published work has ranked in the top 1% by citations of other researchers the world over. Congratulations Dr. Pugh! Source: UHN.ca

It Gets Better with Music: Listening to your favourite music may reduce the effects of visually induced motion sickness. Passengers in a stationary train often feel a false sense of self-motion when a neighbouring train starts to move. Immersive videos and Virtual Reality devices can also create a similar perception of illusory self-motion. These sensations can cause dizziness and nausea known as visually induced motion sickness. Dr. Behrang Keshavarz, Scientist at The KITE R...esearch Institute, recently discovered that when users listen to their favourite playlist, the effects of visually induced motion sickness can be reduced. The research team conducted a study in which eighty participants were asked to view a video of a bike ride through a city. To make the video, a camera was mounted on the handlebars of a bicycle and captured footage of bumpy and even roads. The researchers then assigned study participants to listen to one of the following soundtracks while watching the videos: street sounds captured by the camera different tracks of preselected classical music, ranging from energetic to calming a curated playlist of the participants’ favourite music We found that the nature of the music isn’t a crucial factor for reducing visually induced motion sickness. That is, happy music wasn’t more effective than sad music, and energetic music wasn’t more effective than calm music, explains Dr. Keshavarz. In contrast, whether the music is preferred by the listener does have a significant effect on visually induced motion sickness. When participants were able to select their favourite music to be played while watching the video, they experienced significantly less side effects and felt a greater sense of well-being. The presence of music had a positive effect on the well-being of study participants in general. The study also showed that energetic music created a greater sense of self-motion in participants compared to calm music. The feeling of being transported to another place and the sensations of motion are usually desired for virtual reality applications, including those used in health care and rehabilitation, says Dr. Keshavarz. By allowing users to select their favourite music as part of a soundtrack, application and game developers may be able to reduce unwanted dizziness and nausea. More energetic music may also improve the immersive quality of the experience. Peck K, Russo F, Campos JL, Keshavarz B. Examining potential effects of arousal, valence, and likability of music on visually induced motion sickness. Experimental Brain Research. 2020 Oct. doi: 10.1007/s00221-020-05871-2. Image Caption: First-person video games, such as driving games, can cause visually induced motion sickness. Adding music to these games and virtual experiences can improve the user’s well-being.

Exposing the Enemy Within: Study reveals that ancient DNA regions are key to activating the immune system against cancer. While the immune system is typically seen as key to fighting colds and infections, scientists are finding new and inventive ways to trigger the immune system to kill cancer cells. One such strategy, known as ‘viral mimicry’, was previously discovered by a team of researchers at the Princess Margaret Cancer Centre led by Senior Scientist Dr. Daniel De Carva...Continue reading

Don’t get hooked by phishing emails. Here are some tips for how to spot spam emails and protect your personal information. Learn more about what UHN Research is doing to combat phishing here >> http://www.uhnresearch.ca//protect-yourself-spam-and-phish #getcybersafe #cyber #cybersecurity

The Future of Cancer Treatment: UHN spin-off company launches to expand cancer immunotherapy to more patients. A new cancer biotechnology company, TCRyption Inc., has been launched based on innovative findings from the Princess Margaret Cancer Centre (PM). TCRyption Inc. emerges from the groundbreaking T-cell immunotherapy technologies created by PM Senior Scientist Dr. Naoto Hirano. The company was founded by Dr. Hirano along with pioneers of the T-cell and cancer fields, Dr...s. Tak Mak and Mark Davis. The technology developed by Dr. Hirano belongs to a branch of cancer immunotherapy known as a T-cell receptor (TCR)-based adoptive cellular therapy which helps to stimulate the body’s own immune response to destroy cancer cells. Unfortunately, the effectiveness of this therapy is dependent on the HLA type of the patient (ie, the presence of certain immune molecules, of which there are many types that vary between patients). Due to this constraint, current therapies are generally effective for only a small patient group. Dr. Hirano has overcome this problem through the development of a methodology that can generate an effective personalized therapeutic regimen for any patient’s HLA type regardless of its frequencyan innovation that will greatly expand treatment options and the groups of patients that can benefit from them. "We are very pleased to announce the launch of TCRyption today; such innovative biotech partners embrace the power of immunity to fight cancer but also recognize that many current TCR-based applications will benefit only some patients. Our methodology at TCRyption allows us to bolster precision medicine for all patients and is an important part of helping us move forward together in our common goal to conquer cancer, says Dr. Naoto Hirano. With early support from the Princess Margaret Cancer Centre Innovation Acceleration Fund for developing the technology, company creation activities were led by UHN’s Technology Development & Commercialization team (TDC) and TIO Bioventures with an initial $10 million in seed financing to advance the innovation so that it can help patients. We are thrilled to have TCRyption launched with the core facilities located right here in Toronto with some of the biggest names and pioneers in cancer immunology as part of the team, says Mark Taylor, Director of UHN’s TDC. To learn more about TCRyption Inc., please view the news release here. To read about recent and related findings from Dr. Hirano, published in the journal eLife, click here. Image Caption: Dr. Naoto Hirano, Senior Scientist and Associate Director of Research for the Tumor Immunotherapy Program at the Princess Margaret Cancer Centre, and Scientific Co-Founder of TCRyption Inc.

With the global COVID-19 crisis, we have seen a surge of misinformation and baseless claims falsely associated with many leading health-care institutions worldwide. Unfortunately, external users have been receiving phishing emails claiming to be from the UHN Research domain. These emails do not originate from UHN Research or any affiliated parties. To raise awareness about this issue, and to coincide with Cyber Security Awareness Month, research at UHN has launched a phishing... education webpage for external users. Visit the site by clicking on the following link: http://www.uhnresearch.ca//spam-and-phishing-dont-get-hook Note that the spam and phishing awareness web page is relevant for individuals who do not work at UHN and appear to be receiving spam from uhnresearch.ca. If UHN patients, volunteers or collaborators are receiving spam emails, they are encouraged to contact UHN Digital through internal routes. We are actively working to better understand how our domain names are being misused and to secure our domain name so we can halt these emails at their source. UHN Digital is working to centralize our outbound mail channels and publish domain reputation information that will allow internet service providers to differentiate legitimate emails from spam emails. As a not-for-profit public hospital, UHN never sends unsolicited emails or advertises products or services to patients or the general public. By providing users with tools to help spot phishing emails, we hope to empower users to safeguard their personal information from fraudsters.

Unified for Cancer Research: Network to accelerate precision cancer medicine research launches across Canada. We are one step closer to the future of cancer care with the launch of the Marathon of Hope Cancer Centres Network (MOHCCN). The initiative is being led by the Terry Fox Research Institute and three leading cancer research centres: the Princess Margaret Cancer Centre, British Columbia Cancer and the Montreal Cancer Consortium. This one-of-a-kind network will unite Ca...nada’s top cancer research centres, allowing them to share their clinical and observational data in order to accelerate discovery and innovation in precision medicine, says founding council member and UHN’s Executive Vice President (EVP) of Science and Research, Dr. Brad Wouters. Today represents the beginning with three of these centres and we are excited about the vision for an inclusive cross-Canada network. Precision medicine’s tailored approach to care allows physicians to better predict which treatments and prevention strategies will be successful for each individual patient. By centralizing data from three research institutes, MOHCCN aims to create a high quality and shareable dataset of 15,000 cases in the first five years and 100,000 cases within the decade. The network’s scientists will initially focus on four key themes: immunotherapy and precision cancer medicine treatment, the use of genomic data in clinical decision making, the impact of tumour dynamics on treatment resistance, and the clinical and treatment courses for rare cancer subtypes. The Terry Fox Research Institute developed a secure platform called The Digital Health and Discovery Platform (DHDP) that will centralize patient data from all participating research centres. Operating with the utmost privacy and security, the DHDP is based on a federated data sharing model, which means data from each centre will be stored on local networks and only shared if requested by a MOHCCN scientist. This is a powerful collaborative network that utilizes the joint expertise of clinicians, pathologists, data and laboratory scientists as well as software developers, says Dr. Wouters. We are working with key partners at the Ontario Institute for Cancer Research and the other Cancer Centres to establish the network and work towards collaborative approaches to reduce the burden of cancer on Canadians. For more information about the MOHCCN, please contact MOHCCN Project Manager Sevan Hakgor at [email protected]. To watch a video from the Terry Fox Research Institute on how precision medicine is transforming cancer care, click here. Image Caption: To help accelerate discovery and innovation, the Marathon of Hope Cancer Centres Network will enable three leading research centres to securely share data from patient cohorts receiving precision medicine cancer treatment.

The Krembil Newsletter: Learn about the latest news and research advancements from the Krembil Research Institute. The Krembil is the official newsletter of the Krembil Research Institute (formerly the Toronto Western Research Institute). Research at Krembil is focused on finding innovative treatments and cures for chronic debilitating disorders, including arthritis and diseases of the brain and eyes. Stories in this month’s issue include:... VIRTUAL KREMBIL RESEARCH DAY 2020: Krembil trainees are encouraged to persevere as scientists are needed now more than ever. COMING TOGETHER FOR DEMENTIA: Popular Krembil virtual event explored the future of dementia research and care. NEUROPHYSIOLOGIST JOINS KREMBIL: Dr. Luka Milosevic, biomedical engineer and neurophysiologist, returns to UHN. MORE THAN FACE VALUE: Machine learning enables in-depth mapping of abnormalities caused by trigeminal neuralgia. LOSING SLEEP AFTER CRITICAL ILLNESS: Study links sleep problems after release from intensive care unit with cognitive decline. A PROMISING CANDIDATE: Early data suggest that furosemide may reduce the severity of COVID-19 infection. A MATTER OF PERCEPTION: Disagreement found between self-reported and performance-based measures of physical function. Read these stories here: http://www.uhnresearch.ca/news/krembil-newsletter-14

A Matter of Perception: Disagreement found between self-reported and performance-based measures of physical function. 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 tea...Continue reading

A Promising Candidate: Early data suggest that furosemide may reduce the severity of COVID-19 infection. 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. Image Caption: Furosemide is widely available worldwide and is inexpensive to produce. It has been used as a diuretic to treat high blood pressure for decades.

Thank you Nestlé for your donation of over 100 cases of coffee to UHN Research! Since labs have reopened, this coffee has been helping to keep our staff fueled and smiling each day.

Losing Sleep after Critical Illness: Study links sleep problems after release from intensive care unit with cognitive decline. Most patients often complain of not getting a good night’s rest in the hospital. However, those who are treated for critical illnesses in the intensive care unit (ICU) continue to experience trouble sleeping for a short while after discharge. A new study suggests that sleep fragmentation, or the tendency to wake up repeatedly throughout the night, ma...y be linked to a decline in cognitive performanceie, the brain’s ability to acquire and process informationin ICU survivors at one week of discharge from the unit. About half of patients show signs of cognitive impairment after a critical illness, says Dr. Elizabeth Wilcox, Clinician Investigator at Krembil Research Institute and lead author of the study. While we know that poor sleep is linked to cognitive impairment, we wanted to see whether these factors affected patients after discharge from the ICU and for how long. The study enrolled 150 participants from five ICU wards across Toronto’s academic hospitals. All participants were on a ventilator for at least three days. Of the 102 individuals who survived discharge from the ICU, more than half were found to have cognitive impairment after one week. To assess sleep quality and duration, the researchers used a technique called actigraphy, which is a non-invasive approach that tracks movement. Study participants used a wrist-worn device to track their activity during sleep. Sleep activity was measured at one week, six months and one year following ICU discharge and standardized cognitive tests were performed at each follow-up. Their analysis revealed that fragmented sleep was associated with cognitive impairment at seven days post-ICU. However, no link was found at six or twelve months. Although we were unable to find an association between fragmented sleep and cognitive impairment at six months or one year following discharge, further studies are needed to see whether the effects of poor sleep on cognition linger, explains Dr. Wilcox. Added support to help patients regain healthy sleep patterns after discharge from the ICU may benefit patients and help with their recovery. This work was supported by the Physician Services Incorporated Foundation and the Toronto General & Western Hospital Foundation. Wilcox ME, McAndrews MP, Van J, Jackson JC, Pinto R, Black SE, Lim AS, Friedrich JO, Rubenfeld GD. Sleep fragmentation and cognitive trajectories after critical illness. Chest. 2020 Jul 24. doi: 10.1016/j.chest.2020.07.036. Image Caption: It is often recommended that adults receive seven to nine hours of sleep to function optimally. However, those recovering from a critical illness may experience frequent awakenings throughout the night, which could have an impact on their cognitive ability.

COVID-19 on Ice: UHN’s COVID-19 Biobank provides access to COVID-19 specimens for life-saving research. Sometimes victory requires keeping your enemies close by. UHN Biospecimen Services and leading researchers have established the UHN COVID-19 Biobank to do just that. UHN’s COVID-19 Biobank was born from the launch of the clinical trial known as the Pandemic Response Biobank for Coronavirus Samples, or PRESERVE, lead by Dr. Shahid Husain. UHN Biospecimen Services securely pr...ocesses, stores, and manages biological specimens and accompanying clinical data, and represents a key resource for basic and clinical research at UHN. Since the trial launched on May 5, 2020, over 292 participants have donated over 10,000 specimens to the COVID-19 Biobank. These specimens will be housed indefinitely for future research studies and quality improvement and include blood, blood components, urine, saliva and nasal swabs. Dr. Husain says, The UHN COVID-19 Biobank will help us to understand key aspects of COVID-19, including, how to detect, prevent, manage and treat disease. Many COVID-19 research projects are underway at UHN. These projects are focused on a variety of topics, such as the development of new COVID-19 tests and diagnostics, therapeutic interventions and ways to curb the spread of the disease. Our facility allows for short and long-term storage in liquid nitrogen using best practices. These stringent standards will ensure that samples remain useful for years to come, adds Dr. Neil Fleshner, Medical Director of the UHN Biospecimen Services. Heidi Wagner, the Head of Operations of UHN Biospecimen Services, comments, The UHN COVID-19 Biobank represents a key resource. One that will enable researchers and clinicians to better understand the virus, the immune response to the virus and to develop effective and life-saving countermeasures.