The Next Generation
OICR has many young researchers working hard in the fight against cancer. This is our opportunity to highlight some of their stories – not just about the excellent work they do, but also about what drove them to work in cancer research.
Dr. Brigitte Theriault
Growing up on a farm in rural New Brunswick, Dr. Brigitte Theriault always knew she wanted to be a scientist. But she didn’t always know she wanted to be a cancer researcher.
When she finished her undergrad in Microbiology and Immunology at Dalhousie University, she left school still not sure of what she wanted to do. Instead of continuing on with her education right away, she decided to work, first for a biotech company for the federal government and then in academia to work in osteoporosis research.
During that time a very good friend’s mother was diagnosed with ovarian cancer and, after two years of treatment, unfortunately passed away from the disease. Theriault spent a lot of time at the hospital with the family, something that she says helped her focus on how she could better use her skills as a scientist to help people.
With the work I’m doing today I can see a clear path to the clinic and really feel that my work has the potential to help people. - Dr. Brigitte Theriault
“It marked me,” she says. “Seeing how this disease works first hand is absolutely devastating. You feel so helpless when you see a friend go through something like that, and I thought I could do something to help ensure others don’t have to keep going through the same thing.”
Theriault returned to Dalhousie shortly after to study ovarian cancer. After graduation her husband found a job in Toronto, so she moved and started a postdoctoral fellowship at the Princess Margaret Cancer Centre, where she was hired to investigate a specific oncogene as a potential therapeutic target for ovarian cancer. During her time there she had interactions with the OICR Drug Discovery group and appreciated the guidance they provided. When her supervisor retired, a position coincidentally came up at OICR, so she applied and was hired in 2013.
Our team is more effective and can advance projects really quickly because we have people with different specializations working together in such close proximity - Dr. Brigitte Theriault
Today Theriault is a Research Scientist in the Biology Group in OICR’s Drug Discovery Program. She works on a small team turning discoveries made in the lab into therapies that can benefit cancer patients.
“This is hands down the best environment I’ve ever worked in. I am thrilled that I can work here with these amazing people who are so focused and so driven and learn so much from them,” she says.
Theriault’s group takes proteins and tests whether they have potential to be targets for cancer drugs. They work with other groups in the Drug Discovery team to develop new compounds and test whether they find and destroy the targeted protein. They also have to ensure the new compound works well at killing cancer while minimizing harm to healthy cells.
Theriault feels that collaboration is the key to success in drug discovery. She prefers the way the team works together toward a common goal, instead of in constant competition, like in academic labs. “Our team is more effective and can advance projects really quickly because we have people with different specializations working together in such close proximity. We are very collaborative and we’re all there to advance therapies to patients.”
A good example of this collaboration is the WDR5 target, which stemmed from collaboration with the Structural Genomics Consortium. Her team has been able to advance the WDR5 target to a pre-clinical compound in less than two years.
Theriault would like to stay in the drug discovery field for the foreseeable future and continue her work bringing discoveries to patients. While she doesn’t currently work on ovarian cancer, she enjoys that she’s working closer to the clinical setting than she was while doing basic science. “I am a little bit closer to the patient. With the work I’m doing today I can see a clear path to the clinic and really feel that my work has the potential to help people.”
Dr. Ivan Borozan
Today we know that there are about seven viruses that can cause cancer in humans. If researchers can create vaccines to turn the immune system against these viruses, they can help to prevent certain types of cancer from ever taking hold. This strategy has been successful with vaccines for viruses such as HBV (to prevent liver cancer). But the question remains - are there more cancer-causing viruses out there that we don’t yet know about?
Dr. Ivan Borozan is a Scientific Associate in the lab of Dr. Vincent Ferretti at OICR who is looking to find out. The main aim of his work is to find the association between various pathogens (such as viruses) and cancer, ultimately establishing the complete list of pathogens that can promote or influence the formation of cancer, known as cancerogenesis.
His team is analyzing terabytes of data that have been generated by sequencing cancer tissue samples, and looking for pathogen sequences that could be hiding amongst all the data. When they do find the pathogen, they then need to determine whether the pathogen caused the cancer to develop or whether it was unrelated.
The ultimate goal is to find the link between those pathogens that cause cancer and how that leads to patients developing cancer...then looking at possible vaccine therapies...ultimately stopping cancer before it starts - Dr. Ivan Borozan
If the pathogen found happens to be a virus they look for viral oncogenes (virus genes that are known to turn cells into cancer cells) that are expressed in cancer samples. If a viral oncogene is expressed in cancer cells then they can establish with certainty that particular virus is causing cancer.
The process starts by taking all the millions of reads that have been sequenced from a given patient and aligning them against the reference human genome. Researchers look for the parts that don’t match – essentially extracting all the DNA that’s not human. They then compare these non-human parts to other non-human reference genomes to see if they match another known genome. The non-human DNA found in a patient could be from various types of microbes, viruses or fungi that are naturally present in the human body. Those foreign elements most likely have nothing to do with cancer. But some do, and part of Borozan’s job is to determine which ones are which.
He likens the whole process to finding a needle in a haystack. While there are about seven known viruses that cause cancer, the total number of possible viral species is enormous, so the potential is huge.
“The ultimate goal is to find the link between those pathogens that cause cancer and how that leads to patients developing cancer,” he says. “And then looking at possible vaccine therapies and how they could be used to protect against these viruses, ultimately stopping cancer before it starts.”
Borozan has been passionate about science since he was very young. He was born in Serbia but grew up in France, moving to England to go to university.
There he studied physics, followed by a PhD in theoretical physics, at the University College London. Theoretical physics is a highly specialized branch of physics that uses complicated math models to describe nature. At the time biology was going through a mini-revolution, with the development of new, next-generation technologies that were generating huge amounts of data – a natural fit for Borozan’s interests. He was interested in applying his skills to biological data. “Biology was becoming more quantitative, generating data with which we could better characterize a biological state, which is a very complex thing. That was very exciting.”
You need to collaborate with people from many different fields. You need knowledge from different fields. And you need to integrate that in order to produce interesting results that will eventually help patients - Dr. Ivan Borozan
Borozan began working as a postdoctoral researcher at the University of Toronto studying host- pathogen interactions in hepatitis C infection. It was shortly after the postdoc finished he found an opportunity at OICR in the Ferretti lab. “To me it was a very natural evolution,” Borozan says. “Previously I was looking at a single virus, now I’m looking at every virus.”
At OICR he’s been able to tap into the resources of the Institute, particularly its robust IT infrastructure, and use that to help generate collaborations to get complex work done faster.
“What’s really essential for us is to be able to collaborate with people with biological backgrounds,” he says. “We really need to be able to link the technical, theoretical knowledge with the biological story behind it. Combining the two skill sets is absolutely essential to getting results.”
Borozan’s team recently published an algorithm that improves the taxonomic classification of unknown pathogen sequences using a combination of machine learning, sequence analysis and information theory. The effort is extremely complex – it’s not just looking for a needle in a haystack, it’s looking for a needle in a haystack when you don’t know what the needle looks like.
He says it is a challenge, but one that the team is well equipped to take on. “For this type of work you can’t be on your own,” he says. “Einstein developed his theories essentially on his own. It was Einstein, his pencil and his brain. For us, for this type of science, you need to collaborate with people from many different fields. You need knowledge from different fields. And you need to integrate that in order to produce interesting results that will eventually help patients.”
Dr. Noah Ivers
Whether at work or at home, email is a part of our everyday lives. It also plays a major role in cancer research, where it has facilitated collaboration and helped patients in trials stay better informed about their treatment. But now in a new cancer research project, email itself is the subject of study.
Dr. Noah Ivers, a family physician at Women’s College Hospital, is looking at how to use email to get doctors’ attention and drive them to use Cancer Care Ontario’s Screening Activity Report – in the ultimate hope of increasing screening rates and getting more patients diagnosed earlier.
“The Screening Activity Report is updated monthly with very valuable information about patients who are overdue for screening or those who have received abnormal test results and require follow up,” explains Ivers. “Getting physicians to log in and use this system regularly could make a big difference in screening rates and catching cancer early.”
The problem is, most doctors aren’t logging in. Currently only seven percent of doctors clicked through the monthly email to access the system and less than 40 per cent access the Screening Activity Report over the course of a year.
...knowing how to engage with doctors and optimize the use of existing data systems will help improve patient care in Ontario - Dr. Noah Ivers
With support from the Cancer Care Ontario (CCO)-OICR Health Services Research Network, under an initiative called KT-NET, Ivers is evaluating different approaches to persuasive communication via email to encourage family doctors across the province to use the Screening Activity Report.
Ivers and his team met with frontline doctors to understand why some use the system and why others don’t. They then took this knowledge and developed eight new versions of the email, applying behavioural science to encourage use of the screening database. The reworked emails incorporate different techniques including anticipated regret (described by Ivers as something similar to using a ‘guilt trip’), reminding doctors about the potential rewards in terms of receiving bonuses from the government for reaching screening targets, and providing tips to make it easier to incorporate routine use of the Screening Activity Report. The new monthly emails were launched as an experimental trial in the spring of 2017, with results to be interpreted collaboratively with CCO in the fall.
Ivers is uniquely suited to address this issue. In addition to being a family doctor, he holds a PhD in clinical epidemiology from the University of Toronto’s Institute of Health Policy, Management and Evaluation, and before medicine, he was in business school. “When I was attending business school I found myself wanting to do something that provided an opportunity to help others, which is why I ended up switching to medicine,” says Ivers. “Now with this work I get to use a bit of that business experience in studying systems and using data to support decision making. And I’m able to combine it with my clinical interests and with my research methods training all at once.”
He says he and his team are looking forward to getting the results. “We are excited to see what works in the real world and taking that and making it routine,” he says. “Ultimately, knowing how to engage with doctors and optimize the use of existing data systems will help improve patient care in Ontario.”
Dr. Shannon Gravely
Understanding how public policies affect the basic choices people make in their daily lives can help shape efforts to improve public health and prevent diseases like cancer. Studying those policies and recommending evidence-based solutions falls to researchers such as Dr. Shannon Gravely, a research assistant professor in the Department of Psychology at the University of Waterloo (UW).
Gravely spent her postgraduate education and early career researching access to heart health programs after cardiac diagnoses and events, particularly among women and other vulnerable populations such as ethnic minorities and people of low socioeconomic status. In 2013, Gravely brought that experience to the International Tobacco Control Evaluation Project (ITC Project) at UW, where she now evaluates the impact of evidence-based tobacco control policies on smoking behaviours among 28 participating ITC Project countries. Shannon holds a three-year Career Development Award in Prevention from the Canadian Cancer Society.
I have developed a real passion for analyzing the data and seeing how public health polices can, and do, reduce tobacco-use rates - Dr. Shannon Gravely
Gravely, whose PhD focused on access to rehabilitative care for people with heart failure, saw a natural connection to the ITC Project. “Coming from a cardiac background the link to tobacco really interested me. It was similar in a lot of ways to the research I was doing in understanding patient behaviours, particularity smoking cessation,” she says. In her previous roles, Gravely studied methods for referral to care following a major cardiac event (e.g. heart attack)and conducted a systemic review of why women attend rehabilitation programs in relatively low numbers compared to men.
“I have developed a real passion for analyzing the data and seeing how public health polices can, and do, reduce tobacco-use rates,” says Gravely, who originally joined the ITC Project as a research scientist. The bulk of the information analyzed by Gravely and her colleagues comes from surveys conducted in countries that are signatories to the World Health Organization’s Frame Convention on Tobacco Control (FCTC). This agreement calls on governments to enact demand reduction measures for tobacco such as taxes, warning labels and plain packaging of products.
In a major study, Gravely and her collaborators looked at the implementation and impact of five key evidence-based tobacco control measures from 2007 to 2014: smoke-free environments, cessation treatment programs, cigarette package health warning labels, advertising controls and higher taxes. “There is strong evidence that the FCTC has increased the implementation of strong tobacco control policies worldwide since the treaty came into force in 2005,” says Gravely. “We have even seen that non-signatories nations, such as Argentina, who adopt some of these measures experience a reduction in tobacco use. In particular we found that the implementation of key FCTC demand-reduction measures is significantly associated with lower smoking prevalence.”
Recently, Gravely and her colleagues heard that another significant voice agrees. The World Bank's International Centre for Settlement of Investment Disputes issued the final ruling in a long-running case launched against the government of Uruguay by a large tobacco company. In its decision the Centre agreed with the government that its proposed measures to ban the sale of multiple varieties of a brand (and limit to a single-brand presentation only) and the increase in the size of warning labels was reasonable. In particular, ITC Project data was used a key piece of evidence for Uruguay’s defense team, as it showed that increasing warning labels from 50 per cent to 80 per cent resulted in increased effectiveness of all key health warning label indicators (e.g., increased noticeability of the larger warnings, increased thoughts about quitting, foregoing a cigarette). Indeed, a larger percentage of participants in the study attributed quitting smoking to the larger warnings as compared to when the warnings were smaller.
The case was a win not just for Uruguay and the ITC team, but also for all countries moving forward with strong global tobacco control policies worldwide. “This case was a huge victory for tobacco control and public health,” says Gravely. “It demonstrated that corporate power and money cannot override fair, strong and sound scientific evidence, especially when it comes to people’s lives being at stake.”