Krembil Research Institute welcomes its newest Scientist, Dr. Olga Lucia Rojas. As an immunologist, her focus is on understanding the role of intestinal immune cells in neuroinflammation and neurodegenerative disorders such as Alzheimer disease and multiple sclerosis (MS).
Recent research led by Dr. Rojas, published in Cell, uncovered the cellular mechanism behind the body’s response to inflammation in autoimmune conditions. The findings revealed that a type of white blood cell, known as a plasma cell, in the gut can produce an antibody called Immunoglobulin A (IgA) that is key to fighting infection. These IgA-producing plasma cells can travel from the intestines to the central nervous system where they are found to supress brain inflammation during MS flare-ups.
Dr. Rojas is also working with a research team to understand the immune response to SARS-CoV-2. Their recent publication showed that SARS-CoV-2 antibodies can be detected in saliva, suggesting the generation of a local immune response against SARS-CoV-2 in the oral cavity after infection. With ongoing collaborations, Dr. Rojas hopes to explore the impact of SARS-CoV-2 infection on neurodegenerative disorders as well.
“Every idea and experiment that we create is a challenge brimming with unanswered questions. I am motivated by my colleagues, students and patients to continue this important research with the aim of improving disease outcomes and quality of life for so many,” says Dr. Rojas.
At Krembil, Dr. Rojas will focus on understanding the role of gut bacteria in the production of IgA-producing plasma cells and the mechanisms by which gut-derived immune cells can impact the development and progression of neurodegenerative disorders. Her research has significant implications for new therapeutic approaches for disorders that currently have no cure, such as Parkinson disease.
“My ultimate research goal is to benefit patients,” says Dr. Rojas. “At Krembil, I will be able to collaborate closely with clinicians, scientists and patients. This unique environment makes it the best place to translate basic research from the lab to a clinical setting.”
Dr. Rojas received her MD and PhD from the Pontificia Universidad Javeriana in Colombia before completing a postdoctoral fellowship in Jennifer Gommerman’s lab in the Department of Immunology at the University of Toronto.
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 Research 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. Exp Brain Res. 2020 Oct. doi: 10.1007/s00221-020-05871-2.
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.
Now, recent findings from the same group, published in Nature, reveal a way to enhance the strategy to better target cancer cells.
Viral mimicry involves activating the production of double-stranded RNA (dsRNA) in the cell—a molecule that is typically found in viruses and is a ‘red flag’ that notifies the immune system of an infection. By producing dsRNA in cancer cells, the process mimics an infection and instructs the body to initiate an anticancer immune response.
Until now, the origin of immunogenic dsRNAs were unknown. In the current study, Dr. De Carvalho’s group found that ancient regions of DNA known as short interspersed nuclear elements (SINEs) are the source of these dsRNAs. Furthermore, certain drugs can specifically reactivate SINEs in cancer cells.
Discussing the role of SINEs in health, Dr. De Carvalho comments, “Humans acquired a series of ‘silent’ repetitive elements in our DNA over millions of years of evolution, but it has been unclear why or what purpose they serve. We set out to identify their function and have found that under the right conditions, they can be reactivated and stimulate our immune system.”
The current findings have added to this initial discovery by revealing the existence of a critical enzyme—known as ADAR1—that is used by cancer cells to evade the immune response induced by viral mimicry.
The study found that when cancer cells produce ADAR1, the dsRNA produced by the ancient DNA is disrupted. Furthermore, the research team showed that inhibiting ADAR1 made cancer cells more sensitive to drugs that induce viral mimicry.
“Since the ADAR1 activity is enzymatic, our work provides an exciting new target for drug development efforts and lays the foundation for the development of a completely new class of drugs that are able to exploit these ‘ancient weapons’ in our genome.” says Dr. De Carvalho.
This work was supported by the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, the Ontario Institute for Cancer Research, the São Paulo Research Foundation and The Princess Margaret Cancer Foundation. C O’Brien holds a Tier 2 Canada Research Chair in Translational Research in Colorectal Cancer and D De Carvalho holds a Tier 2 Canada Research Chair in Cancer Epigenetics and Epigenetic Therapy.
Mehdipour P, Marhon SA, Ettayebi I, Chakravarthy A, Hosseini A, Wang Y, de Castro FA, Yau HL, Ishak C, Abelson S, O’Brien CA, De Carvalho DD. Epigenetic therapy induces transcription of inverted SINEs and ADAR1 dependency. Nature. 2020 Oct 21. doi: 10.1038/s41586-020-2844-1.
Princess Margaret Cancer Centre Senior Scientist Dr. John Dick has been elected to the prestigious National Academy of Medicine (NAM). The NAM is one of three academies that comprise the National Academies of Sciences, Engineering, and Medicine in the United States.
The Academy contains over 2,200 members who are recognized for their profound professional achievements in relation to health and medicine. Each year, the NAM elects up to 100 members, of whom 10 are selected from the international stage.
Dr. Dick is globally recognized for his discovery of leukemia stem cells, which was made possible by an assay he developed. The assay involves transplanting cells from either normal or cancer human adult bone marrow into an experimental model to gauge cancer initiation. Using this approach, he revealed that only a small subset of these cells were capable of initiating leukemia and were the main cause of disease relapse. These contributions shaped our understanding of cancer and revealed a new strategy for curing the disease.
Over his prolific career, Dr. Dick has published over 200 peer-reviewed articles, which have garnered over 55,000 citations. His landmark studies are routinely published in widely read scientific journals, including Nature, Science and Cell Stem Cell, and have revolutionized our understanding of leukemia and normal blood development.
The newly-elected class of 2020 was announced at the NAM annual meeting in October. Read more here.
Congratulations to Dr. Dick!
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.
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One in five Canadian adults is currently living with arthritis, a disease-causing inflammation of the joints, which can result in chronic, debilitating pain, reduced mobility and premature disability. Arthritis is the leading cause of disability globally.
To address this growing crisis, the Schroeder Arthritis Institute, launched with a $25 million donation by philanthropists Walter and Maria Schroeder, will help UHN’s innovative arthritis program become a world-class hub for innovation in research, education and patient care.
Krembil Senior Scientists Dr. Robert Inman and Dr. Mohit Kapoor serve as Co-Directors of the Institute. Dr. Inman is a leader in field of ankylosing spondylitis and Dr. Kapoor’s research program is focused on advancing our understanding of osteoarthritis.
“Maria and I have put a great deal of thought into making this gift and ultimately we were persuaded by the vision and leadership of Dr. Kapoor and the arthritis team at UHN,” says Mr. Schroeder. “We want to be part of an effort that will finally put an end to unnecessary pain and suffering from arthritis and related conditions.”
Funds will go toward supporting top scientific talent and providing critical salary and infrastructure resources for the entire research team, which includes 51 scientists and clinician-scientists, 113 trainees and 200 staff.
The Institute will encompass research, education and innovations in clinical activities within four clinical programs: Hand, Orthopedics, Osteoporosis and Rheumatology, with the core goal of pushing the boundaries of discovery, learning and patient care.
The Institute builds on the momentum of the arthritis team’s progress in recent years, including innovations in surgical approaches for bone and joint diseases; new diagnostics and treatments in ankylosing spondylitis, lupus, osteoarthritis, osteoporosis, psoriatic arthritis, scleroderma and sjogren’s syndrome; as well as the development of predictive tools for orthopaedic surgery outcomes. This donation will extend these achievements by enabling the arthritis team to have global impact through the development of early diagnosis, innovative treatments and prevention.
“Our unique approach, creating alignment and synergy between our research and clinical teams, can only serve to help translate discoveries faster, and benefit patients sooner,” says Dr. Brad Wouters, Executive VP, Science & Research, at UHN. “This gift will help solidify UHN’s status as the largest research hospital in Canada and as a leader in arthritis research and clinical care, globally.”
To read more, click here.
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, Drs. 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 frequency—an 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.
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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