Dr. Wang leads the AI team for the Peter Munk Cardiac Centre (PMCC) in developing machine-learning algorithms to help predict the course of disease and help clinicians make decisions to personalize patient care. The prestigious CIFAR Chair will support and advance this work.
In addition to his current role at Techna and PMCC, Dr. Wang is cross-appointed to the Department of Medical Biophysics at UofT and the Vector Institute. He graduated from the Department of Computer Science at Stanford University and worked as an AI scientist at multiple biotech companies, including Illumina and Genentech.
The CIFAR AI Chairs support Canada’s leading role in AI research and training, providing up to $1 million in funding to support the activities of each Chairholder. They are a component of the Pan-Canadian Artificial Intelligence Strategy managed by CIFAR, a $125 million investment to support a national AI research community.
Welcome to the latest issue of The Krembil.
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:
● NEW TALENT JOINS MEDIA TEAM: Twayne Pereira will use his artistic skills and scientific knowledge to promote research.
● SOLVING THE PUZZLE: New tool could provide insights to make cell therapy an effective treatment for vision loss.
● A PAIN IN THE KNEE: Severity of osteoarthritis symptoms linked to predominant type of immune cells in joints.
● CAUSE FOR CONCERN: Higher opioid use found in younger and depressed patients awaiting surgery for osteoarthritis.
● COMPARING MEMORY LANES: UHN researchers help to clarify how temporal lobe epilepsy accelerates forgetting.
Read these stories and more online here. To read previous issues, see the newsletter archive.
The opioid debate is complex: while opioid medications can be beneficial for pain management, in some cases they have been linked to worse outcomes and addiction.
This debate is particularly relevant to osteoarthritis—a condition that can cause persistent and often debilitating joint pain that worsens over time. Along with pain medication, surgery to replace affected joints is often a last resort.
“There exists a lot of unknowns regarding the use of opioid medication in this setting,” says Krembil Clinician Investigator Dr. Raja Rampersaud. “Few guidelines exist on the proper use of opioids for managing osteoarthritis-related pain, and recent evidence suggests that these medications are ineffective. As well, there is increasing evidence that opioid use in these patients may lead to worse surgery outcomes.”
To shed more light on this issue, Dr. Rampersaud and his collaborators initiated a study to explore the effect of opioid use and other factors—such as body mass index, age, level of education and health status—on the outcomes of patients with end-stage osteoarthritis having surgery.
“After analyzing data for over 1,125 patients, we found some concerning trends,” says Dr. Rampersaud. The study revealed that a large proportion of osteoarthritis patients—up to one third—are using opioids. Furthermore, opioid use was higher in younger individuals (those under 65 years of age) and those experiencing symptoms of depression.
“Our findings provide compelling evidence that more rigorous guidelines, and effective and timely alternatives are needed to protect individuals with osteoarthritis from the potential harms of opioid use. Also, given that recent studies have linked opioid use to worse surgical outcomes, carefully considering patient factors, such as age and mental health, could help to counteract these effects and improve the lives of those with osteoarthritis.”
This work was supported by University Health Network’s Arthritis Program and the Toronto General & Western Hospital Foundation.
Power JD, Perruccio AV, Gandhi R, Veillette C, Davey JR, Lewis SJ, Syed K, Mahomed NN, Rampersaud YR. Factors Associated With Opioid Use in Pre-surgical Knee, Hip and Spine Osteoarthritis Patients. Arthritis Care Res (Hoboken). 2019 Jan 10. doi: 10.1002/acr.23831.
A team of researchers at the University Health Network has developed a novel research tool that could help to advance new treatments to reverse vision loss caused by age-related macular degeneration (AMD).
Aging and ‘wear-and-tear’ can take a significant toll on the human body, especially our weight-bearing joints. Osteoarthritis—the most common form of arthritis—is a condition characterized by the progressive loss of cartilage in the joints of the hands, knees, hips and spine. Cartilage is an elastic tissue that covers and cushions bones in the joint, and as it degrades over time, joints become stiff and painful.
While we know that the immune system is involved in disease progression, it is unclear if and how different types of immune cells are linked to the severity of symptoms or quality of life.
To address this gap, a team led by Dr. Sowmya Viswanathan, an Affiliate Scientist at the Krembil Research Institute, analyzed several types of immune cells in the joint fluid of individuals diagnosed with knee osteoarthritis. As part of the study, these individuals completed questionnaires on their symptoms, daily living activity, quality of life, pain, stiffness and joint function prior to receiving treatment.
The researchers found that monocytes and macrophages were the most abundant types of immune cell present within the joint fluid of osteoarthritis patients. Further investigation revealed that particular subtypes of monocytes and macrophages were linked to patient-reported outcomes, especially joint stiffness and function, as well as quality of life.
“Our findings suggest that certain populations of immune cells could serve as indicators of disease severity. They also provide new insights into the biology of osteoarthritis that could inform the development of therapies to slow or stop disease progression,” says Dr. Viswanathan.
This work was supported by the Arthritis Society and the Toronto General & Western Hospital Foundation.
Gómez-Aristizábal A, Gandhi R, Mahomed NN, Marshall KW, Viswanathan S. Synovial fluid monocyte/macrophage subsets and their correlation to patient reported outcomes in osteoarthritic patients: a cohort study. Arthritis Res Ther. 2019 Jan 18. doi: 10.1186/s13075-018-1798-2.
A new study led by Princess Margaret (PM) Cancer Centre Research Director Dr. Aaron Schimmer suggests that an increase in a certain class of fats, known as phospholipids, plays a fundamental role in the initiation and growth of acute myeloid leukemia (AML)—an aggressive form of blood cancer.
Phospholipids have many important roles in the body, including storing energy, relaying messages and serving as the building blocks of life. Because of this, changes in these fat-like substances are linked to a number of diseases, including cancer.
Dr. Schimmer and his team found that loss of a protein known as Taffazin (TAZ) increased levels of the phospholipid phosphatidylserine and decreased the growth and survival of specific AML cells that are known to initiate and maintain disease. Interestingly, their experiments showed that loss of TAZ had no effects on healthy blood cells.
“These findings shed new light on the impact that phospholipids have on leukemia initiation and progression,” says Dr. Schimmer. “Finding ways to change the composition of these molecules in the body may represent a new way to block the development or progression of AML.”
This work was supported by the Canadian Institutes of Health Research, the Ontario Institute for Cancer Research, the Government of Ontario, the National Institutes of Health, the University of Toronto, the PM Cancer Centre, the Lady Tata Memorial Trust and The Princess Margaret Cancer Foundation. Dr. Schimmer holds the Barbara Baker Chair in Leukemia and Related Diseases.
Seneviratne AK, Xu M, Aristizabal Henao JJ, Fajardo VA, Hao Z, Voisin V, Wei Xu G, Hurren R, Kim S, MacLean N, Wang X, Gronda M, Jeyaraju D, Jitkova Y, Ketela T, Mullokandov M, Sharon D, Thomas G, Chouinard-Watkins R, Hawley JR, Schafer C, Yau HL, Khuchua Z, Aman A, Al-awar R, Gross A, Claypool SM, Bazinet R, Lupien M, Chan S, De Carvalho DD, Minden MD, Bader GD, Stark KD, LeBlanc P, Schimmer AD. The mitochondrial transacylase, Tafazzin, regulates for AML stemness by modulating intracellular levels of phospholipids. Cell Stem Cell. 2019 March 28. doi: 10.1016/j.stem.2019.02.020.