“I think pivoting my research during the pandemic helped me prepare to be a clinician-scientist, because nothing ever works out the way you expect it to in research. You always have to adapt and be flexible,” says Dr. Alvin Tieu, winner of The Ottawa Hospital's Worton Researcher in Training Award.Dr. Alvin Tieu knows his EVs – not electric vehicles, but extracellular vesicles. These tiny particles released by cells carry messages that influence the actions of cells around them. Interestingly, EVs could offer new ways to treat disease, but the field is in its infancy with many unknowns.
Dr. Tieu wondered if EVs from stem cells could be used to treat serious lung diseases. While stem cells can do this in the lab, more research is needed to translate this potential into treatments for patients.
“Unfortunately, stem cells are fragile, difficult to manufacture and store, and may trigger unwanted immune reactions when injected,” says Dr. Tieu. “If we use the little particles they release instead, that could offer a more practical method to harness the benefits while overcoming many technical challenges of cell therapy.”
Under the joint supervision of Dr. Manoj Lalu and Dr. Duncan Stewart, Dr. Tieu embarked on a multidisciplinary PhD on this subject, as part of the MD/PhD program at the University of Ottawa, in partnership with The Ottawa Hospital.
Finding knowledge gaps and filling them
First, he systematically looked at what other researchers had already learned from lab experiments of stem cell EVs to treat lung disease. Collecting and analyzing this information was very helpful to a new field that’s trying to figure out how EVs work and the best way to use them. He focused on “mesenchymal” stem cells, which heal by sending signals to other cells rather than creating new tissues.
Based on those studies, Dr. Tieu found stem cell EVs improved outcomes in animal models of acute lung injury, bronchopulmonary dysplasia, and pulmonary arterial hypertension. However, many of the studies did not mention important details like the best tissue source of EVs, what kind of EVs were used and where they travelled in the body. This critical information is needed before human clinical trials can start. Dr. Tieu’s findings were published in the top journal for EV research, and he was asked to present them to hundreds of EV experts at international conferences and workshops.
But he wasn’t done yet. After identifying these significant knowledge gaps in EV research, Dr. Tieu designed lab experiments to help fill those gaps. One example used state-of-the-art live imaging techniques to track where stem cell EVs were going in the body, and whether they were homing to the tissues damaged by lung injury.
Research in the time of COVID-19
"I want a career where I can both treat patients individually, but also make research discoveries that can hopefully improve lives globally,” says Dr. Alvin Tieu.Dr. Tieu’s EV quest was interrupted by the COVID-19 pandemic, which shut down research labs and halted his experiments. Initially a devastating set-back, Dr. Tieu decided to use his experience with animal models of lung disease to create a new mouse model of severe COVID-19 in partnership with Drs. Carolina Ilkow and John Bell. These mice could safely be used by researchers to better understand COVID-19 and test new vaccines and therapies.
“I think pivoting my research during the pandemic helped me prepare to be a clinician-scientist, because nothing ever works out the way you expect it to in research. You always have to adapt and be flexible,” says Dr. Tieu.
When he wasn’t in the lab, Dr. Tieu continued to collect and analyze other people’s EV research. He led and collaborated on eight systematic reviews on various diseases, and taught other students and residents how to appraise research articles and do meta-analyses.
On to the next challenge
Now finished his PhD, Dr. Tieu is doing his residency in anesthesiology. But as he cares for patients, he’s keeping his researcher hat on.
“During the next five years, I’m hoping to tease out the knowledge gaps in anesthesiology, and what questions we can answer that will have the biggest impact on patient care,” he says. “I really want to be a clinician scientist. I want a career where I can both treat patients individually, but also make research discoveries that can hopefully improve lives globally.”
Check out this Q&A to learn more about Dr. Tieu and what inspires him.
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