Researchers Under the Scope

Miniature human brains grown in a Saskatoon lab are upending the way researchers see neurology and immunology. Neuroscientist Dr. Tyler Wenzel is using brain organoids to challenge decades of rodent-based research, charting a new course for precision medicine. As a high school biology teacher, Wenzel's students learned how hearts pump blood and lungs move air. But apart from neurological electrical activity, neither Wenzel nor the textbooks had many clear answers about the brain. During his graduate studies, Wenzel realized the same experimental question tended to produce opposite results for mice and humans. The key difference, he found, lay in how each species' responded to toxins and injury, leaving him skeptical of neurological therapies tested on rodents. Now an assistant professor of psychiatry at the University of Saskatchewan, Wenzel focuses on youth degenerative brain disease and the limits of traditional research models. He grows human brain organoids — "mini brains" — from pluripotent stem cells derived from sources like blood or skin. Measuring two millimetres apiece, those organoids resemble tiny blobs of chewing gum. "We will turn [cells from a patient] into pluripotent stem cells, and we will make their mini brain, and because it has their genetic information, we get a brain that has their pathology," Wenzel said. "If you do that same mutation, often in a mouse, the pathology won't appear. So it allows us to actually get a pathology we can actually study," he said. When Wenzel was first hired at the University of Saskatchewan in 2024, the budget-conscious researcher built his lab on a shoestring, picking up secondhand centrifuges, balances, fridges and freezers from industrial start-ups. That move saved him time, and hundreds of thousands of dollars. "All the money that we started off with, it is literally going to just the research team and directly to the research," Wenzel said, crediting NSERC and SHRF for their support. "I am so grateful." Today, Wenzel studies childhood cerebral X-linked adrenoleukodystrophy (ALD), a rare degenerative brain disease that strikes children, and is fatal when left untreated. His organoids may provide proof of concept for new ways to target the brain and nervous system, without the need for radiation, chemotherapy, and lifelong immunosuppresant drugs currently required for hematopoietic stem cell transplants. "Chemotherapy and irradiation makes holes throughout your whole body. So we can do it in just your brain, just your spinal cord, and then we can inject the immune cells specifically into those locations," Wenzel said. "That eliminates many of the things that make chemotherapy uncomfortable, many of the things that make any sort of stem cell transplant uncomfortable." This spring, Canada's Stem Cell Network singled out Wenzel's work with a Rising Star Award, saying his work demonstrates "leadership, creativity and potential for major impact". If his method shows promise in treating ALD, Wenzel's approach could pave the way for more targeted, effective and far less invasive treatments for a range of degenerative brain diseases.

Yi-Chun Chen (PhD) is taking a close-up look at some of the body's hardest-working cells — the ones often processing an overabundance of modern-day food and nutrients. "From an evolutionary point of view, our cells are not designed to deal with that," said Chen, who joined the department of Anatomy, Physiology, and Pharmacology at the University of Saskatchewan last year as an assistant professor. She said our bodies are pushed into churning out large amounts of insulin rapidly after snacks and meals, "which makes the beta cells work extra hard." Raised in Taiwan and inspired by her grandfather—a retired elementary school science teacher—Chen's fascination with biology first led her to work as a medical laboratory technologist, then to the world of cellular research. Using both rodent and human models, Chen is studying pancreatic beta cells: the way they process peptide hormones like insulin and how their behaviour and function is affected by an excess of nutrients. With high-resolution imaging, she and her team are examining how both humans and mice synthesize, process, and clear peptide hormones. "There are a lot of things we still don't know about peptide hormones, not just in the pancreas, but in the brain, in the gut," she said. "Those are fascinating." Last year, Chen was the recipient of a Canadian Institutes of Health Research Research Excellence, Diversity, and Independence Early Career Transition Award. After moving from UBC to Saskatoon, Dr. Chen said feels considerable support already from her established and mid-career prairie colleagues. "They can mentor us and guide us, and we also have a group of five or six young scientists," she said. "I can envision myself working on many, many interesting projects with them." Her goal today is to identify biomarkers that could predict diabetes far earlier. She hopes to develop biochemical assays that measure proinsulin levels to serve as an early warning system. This could enable interventions months or even years before a traditional diagnosis based on blood glucose levels. "We want to be able to predict the development of, for example, type 1 or type 2 diabetes before they are diagnosed," said Chen. In the long term, Chen envisions both preventative strategies and regenerative therapies to fight diabetes. Stem cell-derived beta cells may be a future solution, she said. "We are making really good progress in Canada, actually. We have clinical trials. We're putting the stem cell–derived beta cells into patients with type 1 diabetes." She hopes this will one day reduce the need for constant insulin injections, even helping curb obesity. "Don't give up," Chen said. "We are passionate and we want to work on many, many things." "If you like it, keep going."

As the world aims to eradicate hepatitis C (HCV) by 2030, Carrielynn Lund and Dr. Alexandra King's team created a how-to guide. Journeys to Wellness: Prairie Hepatitis C Roadmap is a step-by-step guide to tackling a spike of new infections across the three Canadian prairie provinces. Hepatitis C (HCV) causes severe liver disease, and was notoriously difficult to treat until the introduction of direct-acting antivirals a decade ago — antivirals which boast a remarkable 95% success rate. Despite this advancement, Lund and Dr. King say Saskatchewan, Alberta and Manitoba need to know why HCV cases keep rising, particularly in jails, in remote communities, and in people who lack adequate housing and nutrition. The virus is not picky, as Carrielynn Lund learned when she was first diagnosed in the 1990s. Her doctor wrongly told her back then the blood-borne illness could be spread only through injection drug use. Shocked, Lund said "I went out of that room and drove home thinking, oh my God, I'm gonna die." A single mother of two, she resumed her professional life and never disclosed that "dark, dirty secret" until nearly 20 years later, as she became friends with Dr. King. The Waniska team, led by Saydi Harlton, brought together researchers, health professionals, and people who've lived with hepatitis C in sharing circles, workshops and interviews. "The stigma around this needed to be addressed and I wanted to be a part of it," said Lund. "People often feel really alone in this journey, and it's so important that we create spaces where they can share their stories and be heard." Participants identified barriers to care, including confidentiality breaches, misinformation and inadequate access to testing. "My priority right now may or may not be my hepatitis C. It might be, where am I going to sleep today? Or, what food am I going to be getting?" said Dr. King. In the Roadmap, King said the disproportionately high number of cases in Indigenous people shows a need for true elimination strategies, rather than pockets of "little pilot projects." "There aren't necessarily a lot of resources, so you're dealing with fairly fragile systems," Dr. King noted. Recent provincial government decisions to axe needle exchanges, and cut public transportation routes to remote and northern communities have taken their toll, she added. Given the hurdles faced by Indigenous and two-spirit people, both Dr. King and Lund say prairie people need culturally informed care. They point to Indigenous-led hepatitis C elimination strategies with predictable funding and resources. "It really helps you to understand the importance of really good evidence-based policy that supports people and meet them where they're at," Dr. King said. Lund and Dr. King believe making a fiscal case for early detection and treatment may also swing policy-makers back toward patient-centred care. Peer support also plays a role, Lund said. "When someone who has been through it helps a newly diagnosed person, it can truly change everything for them," she said.

In this episode, we gain insight into Dr. Sarah Forgie, the new Dean of the College of Medicine. She discusses her innovative teaching methods, her career as a pediatric infectious disease specialist, and her vision for advancing Saskatchewan's College of Medicine. Dr. Forgie also shares the story behind her decision to learn the ukulele. Born to family physicians, Dr. Forgie grew up in Lynn Lake, Manitoba, a remote fly-in mining community. Her family later relocated to Winnipeg, where Dr. Forgie credits much of her motivation to her mother, who encouraged her to pursue both medicine and leadership roles. As a pediatrician and professor at the University of Alberta, Dr. Forgie's journey into university leadership can be traced back to her willingness to deploy creative teaching methods. Faced with the challenge of teaching infectious diseases to first-year medical students, she re-wrote the Talking Heads hit "Psycho Killer" to reinforce best practices in treating Streptococcal pharyngitis -- with ukulele accompaniment. It worked. Those who attended her "Take Five" bacteriology lectures at the University of Alberta retained 98% of the key concepts, compared to a 50-60% retention rate among students in standard classes. Dr. Forgie strived to instill strong clinical reasoning, and challenged her students to present key concepts in their own creative ways. "With every session, I would do something, they would do something, and it just made it a fun environment," she said. Following her appointment as Saskatchewan's first full-time female Dean of Medicine on July 1, 2024, Dr. Forgie returned to clinical service this fall as a pediatrician at the Jim Pattison Children's Hospital in Saskatoon. In her role as Dean, she aims to strengthen connections between the College of Medicine and Saskatchewan's medical practitioners. "What I would love to see in Saskatchewan is that every physician approaches their work with an academic lens," Dr. Forgie said. This 'lens' may encompass participating in clinical trials, exploring ways to alleviate physician workloads, or collaborating with learners, she said. Engagement with Indigenous communities remains a critical component of Dr. Forgie's vision for wellness. "I am all about collaboration... with First Nation, Inuit, and Métis communities to better prepare our trainees to work within these communities," she stated, affirming her commitment to cultural sensitivity in healthcare. As a lifelong resident of the prairies, Dr. Forgie understands the isolation often experienced in rural medicine. She aims to foster connectivity among healthcare providers and new learners. "How can we help and how can we reduce some of those feelings that you're having around burnout and frustration?" she asked. "Helping with that leads to a virtuous cycle of how do we make things better in Saskatchewan?"

Growing up in Columbia had a profound impact on Dr. Juan-Nicolas Pẽna-Sànchez. In this episode, hear why the former family physician pivoted, becoming Saskatchewan's lead in finding the best ways to treat Crohn's disease and ulcerative colitis in rural and Indigenous patients. Even as a teenager, Juan-Nicolás Peña-Sánchez could see stark differences in health for those who had medical coverage — and those without, thanks to his stepfather, an emergency department physician. "I used to go with him sometimes on shifts to learn and shadow him," said Peña-Sánchez said. "The healthcare system was quite fragmented and most of the population was not covered." In the 1990s, the Colombian healthcare system was reformed within the context of "neoliberal health reforms" promoted by the World Bank and International Monetary Fund, integrating privatization of the care delivery system, individual health insurance as the mechanism for receiving healthcare, the development of basic benefit plans, among other reforms. "It changed the way to practice medicine," said Peña-Sánchez, who observed among his stepfather and his medical school instructors' grew dissatisfied with limits imposed under the new tiered coverage system. Peña-Sánchez went on to work for non-governmental organizations in Bogotá, providing healthcare to individuals living in marginalized communities and with limited resources. After witnessing the inequities amplified by healthcare reforms, Peña-Sánchez began to analyze health systems themselves. He moved to Spain, Poland, and France to continue his graduate studies, and then to the University of Saskatchewan, where he joined the Department of Community Health and Epidemiology as an associate professor after researching physician satisfaction and alternatives to 'fee-for-service' payment models. Still, Peña-Sánchez missed interacting directly with patients, and hearing their stories. Through the College of Medicine, he began learning about inflammatory bowel disease (IBD) and moved his focus to innovative models of care for IBD. Canada's high prevalence of IBD, particularly Crohn's disease and ulcerative colitis, stood in stark contrast to his experiences in Colombia. Dr. Peña-Sánchez formed the IBD among Indigenous Peoples Research Team after realizing in 2017 there was virtually no data on the incidence, prevalence or treatment of IBD for First Nations and Metis people. "We learned that IBD is increasing among First Nations in Saskatchewan," said Peña-Sánchez, who started zeroing in on disparities in those patients' healthcare access and outcomes. Peña-Sánchez and his team explain their findings in this episode. "Having that regular access is critical," he said, advocating for innovative approaches to healthcare delivery. Dr. Peña-Sánchez also explored the potential of virtual care, particularly telephone consultations, to improve healthcare access for rural populations. He found rural residents were more satisfied with telephone care compared to urban dwellers, an insight that underscores the need for adaptable healthcare models. Currently, Dr. Peña-Sánchez is focused on patient navigation interventions to support individuals with chronic gastrointestinal conditions, particularly in rural Saskatchewan and for Indigenous community members. His research aims to improve access to specialized IBD care and patient outcomes through peer support and patient navigators.

As an undergrad, Daniel Fuller didn't have a car, nor was he keen on taking the bus. "I rode my bike to university every day in the fall and then just kept on going and never stopped," said Fuller, a former national and international canoe/kayak athlete. As he pedaled, Fuller watched the way people used trails, sidewalks and roads. "I really started to get into active transportation, how people move around cities and how we can get people active -- outside of the sport environment," said Fuller, now an associate professor in Community Health and Epidemiology at the University of Saskatchewan. Fuller moved to Montreal for his doctorate as the city launched its bicycle-taxi program. After the widespread installation of shared-use bicycles, Fuller observed no changes in collisions or crashes. However, a significant number of people started to combine biking with walking, and public transit. Fuller said Montreal succeeded because the city went big, launching more than 5,000 rental bicycles at 405 docking stations. "They work on network effects: people being able to find them, people being able to use them, and integrate them with their mobility," said Fuller. His goal is to link active transportation in urban planning to measurable gains in public health outcomes. "If we implement a bike lane, how much health benefit is there? Or how many health dollars might we save? Because health care is our biggest expenditure provincially, and if we can save money on health, then that's really, really important." For almost everyone, Fuller said five to ten more minutes of walking each day would be "extremely beneficial." "It improves mental health, reduces depression, improves type 2 diabetes, improves chronic obstructive pulmonary disease, and prevents certain forms of cancer," he said. Technology plays a big role in Fuller's work. From 2016-2022, he was a Canada Research Chair in Population Physical Activity at Memorial University, and he remains a Principal Investigator on the INTERventions, Research, and Action in Cities (INTERACT) team. He's studied wearable devices to assess their accuracy, and how much they motivate people to stay physically active. "The jury's kind of out on that," said Fuller, who noted Fitbits and Apple Watches tend to give users an initial activity boost, which fades after a year or two. Instead, he said population density is far more effective in raising the number of minutes people move each day. Fuller said city planners rely on traffic counts to decide whether or not an intersection should be expanded or changed — but there's virtually no information to accurately quantify sidewalk use, or the health costs of urban sprawl. As the co-principal investigator of the CapaCITY/É Healthy Cities Implementation Science Team, he's trying to get a detailed handle on why some cities succeed with active transportation, while others struggle. "There's a whole political hierarchy," said Fuller. "Who's paying, how much are they paying, how fast does it have to happen, all these kinds of questions that we don't have good generalized kind of science about yet."

"Pushing politicians to do what is good for the health of the people, there's no way around it," said Dr Jacob Alhassan. Born and raised in a rural Ghanaian village, Alhassan grew up without electricty and paved roads. He watched women die in childbirth. He grew resentful of health systems that left the poorest people to fend for themselves, while the rich thrived. Alhassan decided to take action. At first, he thought he would study hard to become a local hospital administrator. Partway through his university years, Alhassan began to dream even bigger. In this episode, he looks back at his arrival in Saskatoon, and how his trajectory to becoming an assistant professor of Community Health and Epidemiology was forever changed by provincial austerity measures that wiped out the Saskatchewan Transportation Company (STC). Billed as a cut that would save taxpayers $85 million dollars over five years, Alhassan studied Hansard and the full debate around the public transit network's closure. He found little evidence supporting the decision to cut it. "We have a political system that is not necessarily arranged for the well-being of average people," said Alhassan, who still remembers travelling to towns and cities across Saskatchewan to interview people devastated by the closure of the intercity bus service. He said the cuts "radically changed" some people's lives, in some cases shortening them. Losing the parcel service also cost the provincial health care system more, with patients delaying medical care, and pharmacists throwing out delayed and weather-damaged medication and vaccines. "It's literally a might-makes-right sort of thing, where the most powerful people make decisions that deeply impact the lives of people who don't really have the voice to raise their concerns or to be heard," Alhassan said. Today, Alhassan's looking more closely at health outcomes tied to public transportation, and their financial impact on taxpayers. He's also one of the academic co-leads of the University of Saskatchewan's Certificate in Global Health. "You cannot do this type of work to improve people's health if you disconnect yourself from the politics," said Alhassan. "That's not going to happen if I kind of sit in the ivory tower and kind of disconnect myself from the political aspect of this. I strongly believe in that."

Daphne Yau can trace her interest in endocrinology back to a beta-cell physiology experiment during her master's degree, working with laboratory mice with Type 2 Diabetes. "It was the part of the pancreas that makes insulin," she said. "It was fascinating. It also made me realize that maybe pure laboratory research wasn't quite for me." From there, her interest in hormones and fluctuating blood sugar levels grew. Yau is no stranger to medicine. Her mother was a pharmacist, while her father and aunt both worked as physicians. Following in their footsteps, Lou completed her pediatrics residency at Queen's University, with fellowship training at McGill. She then focused on congenital hyperinsulinism at the Children's Hospital of Philadelphia and Royal Manchester Children's Hospital. She still remembers her residency, and meeting a premature baby with a rare genetic disorder in neonatal intensive care. "The blood sugars were horrendously low right from the start," Yau said. "Their brain uses most of that glucose, so that's why it's so critical in that period that they get a steady supply." Together with an endocrinologist and a multi-disciplinary team, Yau and her colleagues traced back the root of the hyperinsulinism — the infant's mother and grandmother also suffered from rare forms of diabetes. Unregulated, plummeting blood sugar levels in infants can cause brain injuries and permanent neurological damage, Yau said. "Your brain can't really store much in the way of glucose and it can't make it on its own the way some other tissues and organs in the body can," said Yau. "If you test a child who's had hypoglycemia when they're two or four, you may not actually pick up on this. Not till maybe later on, when they're in school and they're struggling." Yau joined the College of Medicine five years ago as a pediatric endocrinologist and assistant professor of pediatrics. Today, she's based at the Jim Pattison Children's Hospital. Her research focuses on understanding and addressing congenital hyperinsulinism, as well as screening for diabetes and other metabolic disorders. In this episode, Dr. Yau pointed to recent success with a project inspired by Dr. Mark Inman. Together, their team is trying to improve diabetes screening and education in northern Saskatchewan, particularly for Indigenous children and teenagers. She said the heel prick hospitals often perform on newborns inspired them. "Could someone at home prick their finger, put some few drops of blood on this card and have their A1C measured that way as opposed to having to go to the lab?" Yau said. The results to date show promise, which could make it easier to screen young patients in remote communities for diabetes. Yau is also working with researchers in the United Kingdom who study blood sugar dysregulation in infants, exploring alternative treatments and lower doses of medications such as diazoxide, to mitigate side effects. "What are the levels we really should be targeting to minimize the potential for long-term harms?"